Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00520130
• Collaborator: (none)
• Enrollment: 92
• Location: 1
• Arms: 2
• Actual Duration (Months): 134
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Background:

Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without a human leukocyte-antigen (HLA) tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patients immune system attacks the transplanted donor cells.

This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.

Objectives:

To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.

To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

• Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.

• Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donors stem cells and immune cells 2 days after completing the conditioning regimen.

Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.

...

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; Hodgkin's Lymphoma; Non-Hodgkin's Disease; Acute Leukemia; Multiple Myeloma	Biological: Rituximab; Drug: Cyclosporine; Drug: Allogenic stem cell transplant (ASCT); Drug: Conditioning Chemotherapy; Drug: TMS; Drug: FLAG; Drug: EPOCH-F; Biological: Alemtuzumab	Phase 1/Phase 2

Detailed Description

Background:

• The major limitations to the broader applicability of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignancies are lack of suitable donors and therapy-related toxicities which include delayed and incomplete immune reconstitution and graft-versus-host disease (GVHD). Based on the theory that the rapid establishment of donor chimerism was essential for an optimal graft-versus-tumor effect, we have employed a strategy of targeted immune depleting chemotherapy prior to reduced-intensity allogeneic HSCT. It is our intent to investigate this approach in the setting of human leukocyte-antigen (HLA)-matched unrelated donors in a pilot manner.

• A clearly superior GVHD prophylaxis regimen has not been established in the unrelated donor transplant setting. The best results that have been reported are with the combination of alemtuzumab plus cyclosporine [AC] and the combination of tacrolimus, methotrexate, and sirolimus [TMS]. These two regimens work by mechanisms which are biologically distinct and potentially have markedly different effects upon immune reconstitution that have not been well studied. In addition, neither of these regimens has been assessed for their effects on chronic GVHD using the National Institutes of Health (NIH) Consensus Conference Criteria. It is our intent to study the effects that these two regimens have on immune reconstitution and chronic GVHD in the setting sequential targeted immune-depleting chemotherapy and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors.

Objectives:

• Primary objectives:

1. to assess the effects of two biologically distinct GVHD prophylaxis regimens, TMS and AC, on immune reconstitution in patients receiving targeted-immune depletion and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors. As part of a comprehensive assessment of immune reconstitution, the primary immunologic endpoint will be the determination of cluster of differentiation 4 (CD4)+ T cell receptor V BETA repertoire by complementarity determining region 3 (CDR3) spectratyping at 3 months post-transplant.

2. to assess overall safety of these two regimens in this setting, as determined by engraftment, acute GVHD, early and late treatment-related mortality, and overall survival.

3. to determine and monitor incidence, organ severity and overall severity of chronic GVHD prospectively using the newly developed NIH Consensus Conference diagnosis and staging criteria and preliminarily validate those tools for use in clinical practice and trials.

• Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics, and assessment of those patients who receive higher doses of anthracyclines for long and short term toxicities

Eligibility:

• Adults (18-74 years) with advanced or high risk hematologic malignancies including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-hodgkin lymphoma (NHL), hodgkin lymphoma (HL), chronic myelogenous leukemia (CML), multiple myeloma, and myeloproliferative disorder (MPD) who lack a suitable HLA matched sibling.

• An unrelated donor matched at a minimum of 7 of 8 alleles (HLA-A,-B,-C, and DRB1) by high resolution typing, identified through the National Marrow Donor Program.

• Life expectancy of at least 3 months, Eastern Cooperative Oncology Group (ECOG) less than or equal to 2 and relatively normal major organ functions.

Design:

• Patients will receive disease-specific induction chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-fludarabine (F)/rituximab (R) or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)) prior to transplant for disease control and immune depletion. If disease is controlled (greater than partial response (PR)) and immune depletion objectives have been met, patients may forgo induction chemotherapy and move forward to the transplant conditioning regimen.

• All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m(2)/day intravenous (IV) for 4 days and fludarabine 30 mg/m(2)/day for 4 days.

• Patients will be stratified according to degree of HLA-match and randomized at the time of enrollment to one of two GHVD prophylaxis regimens:

• Group 1: Tacrolimus starting 3 days before stem cell transplant (SCT), and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.

• Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

• A maximum of 105 patients will be enrolled and randomly assigned to the two arms in order to yield 44 patients per arm (88 total patients) who are able to be evaluated for development of severe chronic GVHD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders
• Actual Study Start Date: Oct 30, 2007
• Actual Primary Completion Date: Oct 14, 2015
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A - Tacrolimus, methotrexate, sirolimus (TMS) Arm TMS Arm	Biological: Rituximab; Rituximab: 375 mg/m(2) intravenous (IV), day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.; Other Names: Rituxan ; Drug: Allogenic stem cell transplant (ASCT); Allogenic stem cell transplant; Drug: Conditioning Chemotherapy; Fludarabine:30 mg/m(2) per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m(2) per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m(2) per day IV infusion, Daily on days 6, -5,-4, and -3; Drug: TMS; Tacrolimus: starting day -3 before transplant, given initially at 0.02 mg/kg/day CIV. Continue IV and then switch to an equivalent oral dose (when patient taking po) titrated for a goal level of 5 to 10 ng/ml; Sirolimus: given as an initial loading dose of 12 mg p.o. on day -3 pre-transplant, 4 mg starting day -2 pre-transplant and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post-transplant. Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-transplant as tolerated.; Other Names: Prograf ; Drug: FLAG; Fludarabine:25 mg/m(2) per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m(2) IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy; Other Names: Fludarabine+high-dose cytarabine+G-CSF (Filgrastim)) ; Drug: EPOCH-F; Fludarabine:25 mg/m(2) per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m(2) per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine:0.4 mg/m(2) per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m(2) IV infusion over 30 minutes on day 5
Experimental: B - Cyclosporine (AC) Arm AC Arm	Biological: Rituximab; Rituximab: 375 mg/m(2) intravenous (IV), day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.; Other Names: Rituxan ; Drug: Cyclosporine; Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if graft versus host disease (GVHD) does not develop.; Other Names: Neoral ; Drug: Allogenic stem cell transplant (ASCT); Allogenic stem cell transplant; Drug: Conditioning Chemotherapy; Fludarabine:30 mg/m(2) per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m(2) per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m(2) per day IV infusion, Daily on days 6, -5,-4, and -3; Drug: FLAG; Fludarabine:25 mg/m(2) per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m(2) IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy; Other Names: Fludarabine+high-dose cytarabine+G-CSF (Filgrastim)) ; Drug: EPOCH-F; Fludarabine:25 mg/m(2) per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m(2) per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine:0.4 mg/m(2) per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m(2) IV infusion over 30 minutes on day 5; Biological: Alemtuzumab; Alemtuzumab:20 mg/day IV over 8 h on days 8 to 4 pre-transplant.; Other Names: Campath

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD) [6 months]

   Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.

2. Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD) [2 years post transplant]

   Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.

3. Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells [Recipient recovery at 6, 12 and 24 months post transplant]

   The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.

4. Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells [Recipient recovery at 6, 12 and 24 months post transplant]

   The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.

5. Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire [Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant]

   Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.

6. Changes in CD8 T Cell Receptor Vbeta Repertoire [Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant]

   Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.

Secondary Outcome Measures

1. Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD) [6 months]

   Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.

2. Toxicities [103 months and 22 days]

   Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

3. Days to Engraftment of Neutrophils [2 years]

   Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3).

4. Days to Engraftment of Platelets [2 years]

   Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support

5. Days to Engraftment of Lymphocytes [2 years]

   Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3).

6. Overall Survival [Patients were followed for an average of up to 5 years.]

   Time between the first day of transplant to the day of death.

7. Early Treatment Related Mortality [Less than or equal to 28 days after transplantation]

   Any death occurring within 28 days after transplantation in a patient in continuous remission.

8. Percentage of Participants With Late Treatment Related Mortality [Greater than 28 days after transplantation]

   Any death occurring 28 days or more after transplantation in a patient in continuous remission.

9. Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant [Day 0, 1 week and 2 weeks]

   During depletion of lymphocytes during transplant conditioning, levels of homeostatic cytokines increase in the blood. These then decline with the expansion of new donor-derived cells. The rapidity of decline may predict acute graft versus host disease (AGVHD). Decline in cytokine IL-7 will be assessed by the enzyme-linked immunosorbent assay (ELISA).

10. Immune Reconstitution of Normal Killer (NK) Cells [2 weeks, and 1, 3, 6, 12, and 24 months post transplant]

    Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

11. Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations [2 weeks, and 1, 3, 6, 12 and 24 months post transplant]

    Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

12. Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations [2 weeks, 1, 3, 6, 12 and 24 months post transplant]

    Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• ELIGIBILITY CRITERIA RECIPIENT ON STANDARD CARE THERAPY:

• The patient is 18-74 years of age.

• The patient has a potentially suitable 8/8 donor if they are between the ages of 69-74 years of age or a potentially suitable 8/8 or 7/8 unrelated donor(s) in the National Marrow Registry or Other Available Registry if they are between the ages of 18-74.

• The patient currently does not meet the protocol s eligibility/enrollment criteria for any reason.

• There is a high likelihood that the patient, in the opinion of the principal investigator (PI) or lead associate investigator (LAI), will meet the protocols eligibility/enrollment criteria to proceed to transplant after standard therapy is completed.

• The patient or legal guardian is able to give informed consent.

EXCLUSION CRITERIA RECIPIENT ON STANDARD CARE THERAPY:

• Human immunodeficiency virus (HIV) infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.

• Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven Z Pavletic, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 14, 2018
• Informed Consent Form - Oct 29, 2018

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. doi: 10.1182/blood-2011-09-378398. Epub 2012 Jan 30.
• Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. Epub 2006 Sep 18. Review.
• Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G, Schubert M, Berger A, Bross P, Chien JW, Couriel D, Dunn JP, Fall-Dickson J, Farrell A, Flowers ME, Greinix H, Hirschfeld S, Gerber L, Kim S, Knobler R, Lachenbruch PA, Miller FW, Mittleman B, Papadopoulos E, Parsons SK, Przepiorka D, Robinson M, Ward M, Reeve B, Rider LG, Shulman H, Schultz KR, Weisdorf D, Vogelsang GB; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006 Mar;12(3):252-66.
• Shaffer BC, Modric M, Stetler-Stevenson M, Arthur DC, Steinberg SM, Liewehr DJ, Fowler DH, Gale RP, Bishop MR, Pavletic SZ. Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia. Exp Hematol. 2013 Sep;41(9):772-8. doi: 10.1016/j.exphem.2013.04.015. Epub 2013 May 18.

• Responsible Party: Steven Pavletic, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00520130
• Other Study ID Numbers: 070195; 07-C-0195
• First Posted: Aug 23, 2007
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Steven Pavletic, M.D., Principal Investigator, National Cancer Institute (NCI): Unrelated Donors; Reduced Intensity Stem Cell Transplant; Leukemia; Lymphoma; Allogeneic Stem Cell Transplant; Myelodysplastic Syndrome; Multiple Myeloma
• Additional relevant MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Preleukemia; Myelodysplastic Syndromes; Cytarabine; Cyclosporine; Rituximab; Alemtuzumab; Fludarabine; Cyclosporins

Study Results

Participant Flow

Pre-assignment Detail	There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Period Title: Overall Study
STARTED	44	45
COMPLETED	39	44
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	Cyclosporine (AC) Arm	Total
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.	Total of all reporting groups
Overall Participants	44	45	89
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 86.4%	41 91.1%	79 88.8%
>=65 years	6 13.6%	4 8.9%	10 11.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.92 (14.68)	47.89 (13.4)	47.90 (14.04)
Sex: Female, Male (Count of Participants)
Female	16 36.4%	15 33.3%	31 34.8%
Male	28 63.6%	30 66.7%	58 65.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.5%	2 4.4%	4 4.5%
Not Hispanic or Latino	42 95.5%	43 95.6%	85 95.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 6.8%	1 2.2%	4 4.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 6.8%	4 8.9%	7 7.9%
White	38 86.4%	39 86.7%	77 86.5%
More than one race	0 0%	1 2.2%	1 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	44 100%	45 100%	89 100%
Histology (Count of Participants)
Non Hodgkin's Lymphoma (NHL)	11 25%	14 31.1%	25 28.1%
Hodgkin's Lymphoma (HL)	5 11.4%	5 11.1%	10 11.2%
Chroni Lymphocytic Leukemia (CLL)	9 20.5%	9 20%	18 20.2%
AML/MDS	6 13.6%	5 11.1%	11 12.4%
Chronic Myeloid Leukemia (CML)	4 9.1%	1 2.2%	5 5.6%
CTCL/PTCL	3 6.8%	2 4.4%	5 5.6%
Acute Lymphoblastic Leukemia (ALL)	2 4.5%	2 4.4%	4 4.5%
Multiple Myeloma (MM)	1 2.3%	1 2.2%	2 2.2%
Other	3 6.8%	6 13.3%	9 10.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)
Description	Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Number (95% Confidence Interval) [percentage of participants]	42 95.5%	38 84.4%

2. Primary Outcome

Title	Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)
Description	Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.
Time Frame	2 years post transplant

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Moderate or Severe cGVHD	50 113.6%	12 26.7%
Severe cGVHD	28 63.6%	5 11.1%

3. Primary Outcome

Title	Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells
Description	The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.
Time Frame	Recipient recovery at 6, 12 and 24 months post transplant

Outcome Measure Data

Analysis Population Description

A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	28	28
6 mo (TMS=28; AC= 28)	24	1
12 mo (TMS=25; AC= 21)	22	7
24 mo (TMS=18; AC= 13)	20	25

4. Primary Outcome

Title	Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells
Description	The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.
Time Frame	Recipient recovery at 6, 12 and 24 months post transplant

Outcome Measure Data

Analysis Population Description

A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	28	28
6 mo (TMS=28; AC= 28)	20	3
12 mo (TMS=25; AC= 21)	17	6
24 mo (TMS=18; AC= 13)	16	6

5. Primary Outcome

Title	Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire
Description	Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Time Frame	Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant

Outcome Measure Data

Analysis Population Description

The original intention was to perform these assays on the first 10 pts within each arm. One pt died within the first mo., others died within the 1st yr. Not all donors gave consent for research analyses to be done on their cells, hence cells from those donors were not available.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	8	9
1 month	48	90
3 months	31	66
6 mo (TMS=7; AC= 9)	35	75
12 mo (TMS=7; AC=9)	30	67
Donor CD4 cells (TMS=8; AC=8)	23	22

6. Primary Outcome

Title	Changes in CD8 T Cell Receptor Vbeta Repertoire
Description	Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.
Time Frame	Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant

Outcome Measure Data

Analysis Population Description

The original intention was to perform these assays on the first 10 pts within each arm. One pt died within the first mo., others died within the 1st yr. Not all donors gave consent for research analyses to be done on their cells, hence cells from those donors were not available.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	8	9
1 month	62	78
3 months	54	81
6 mo (TMS=7; AC= 9)	62	84
12 mo (TMS=7; AC= 9)	55	89
Donor CD8 cells (TMS=8; AC= 8)	47	43

7. Secondary Outcome

Title	Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
Description	Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Number (95% Confidence Interval) [percentage of participants]	13 29.5%	21 46.7%

8. Secondary Outcome

Title	Toxicities
Description	Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame	103 months and 22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	44	45
Number [participants]	43 97.7%	42 93.3%

9. Secondary Outcome

Title	Days to Engraftment of Neutrophils
Description	Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

One myeloma patient had graft failure in the AC Arm. 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC Arm)
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Median (Full Range) [Days to neutrophil engraftment]	11	9

10. Secondary Outcome

Title	Days to Engraftment of Platelets
Description	Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC Arm)
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Median (Full Range) [Days]	19	14

11. Secondary Outcome

Title	Days to Engraftment of Lymphocytes
Description	Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC Arm)
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Median (Full Range) [Days]	16	76

12. Secondary Outcome

Title	Overall Survival
Description	Time between the first day of transplant to the day of death.
Time Frame	Patients were followed for an average of up to 5 years.

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Median (95% Confidence Interval) [Months]	41.7	18.8

13. Secondary Outcome

Title	Early Treatment Related Mortality
Description	Any death occurring within 28 days after transplantation in a patient in continuous remission.
Time Frame	Less than or equal to 28 days after transplantation

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (C) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Number [participants]	1 2.3%	0 0%

14. Secondary Outcome

Title	Percentage of Participants With Late Treatment Related Mortality
Description	Any death occurring 28 days or more after transplantation in a patient in continuous remission.
Time Frame	Greater than 28 days after transplantation

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	39	42
Number (95% Confidence Interval) [percentage of participants]	28 63.6%	29 64.4%

15. Secondary Outcome

Title	Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant
Description	During depletion of lymphocytes during transplant conditioning, levels of homeostatic cytokines increase in the blood. These then decline with the expansion of new donor-derived cells. The rapidity of decline may predict acute graft versus host disease (AGVHD). Decline in cytokine IL-7 will be assessed by the enzyme-linked immunosorbent assay (ELISA).
Time Frame	Day 0, 1 week and 2 weeks

Outcome Measure Data

Analysis Population Description

Following the focus on chronic graft-versus host disease (GVHD) as a primary outcome measure in 2011, this measure was not assessed.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (C) Arm
Arm/Group Description	Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	0	0

16. Secondary Outcome

Title	Immune Reconstitution of Normal Killer (NK) Cells
Description	Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame	2 weeks, and 1, 3, 6, 12, and 24 months post transplant

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	38	39
2 weeks	123	15
1 month	270	31
3 months	134	124
6 months	136	202
12 months	134	150
24 months	133	307

17. Secondary Outcome

Title	Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations
Description	Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame	2 weeks, and 1, 3, 6, 12 and 24 months post transplant

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	38	39
2 weeks	171	0
1 month	285	21
3 months	297	61
6 months	387	121
12 months	447	132
24 months	451	373

18. Secondary Outcome

Title	Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations
Description	Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.
Time Frame	2 weeks, 1, 3, 6, 12 and 24 months post transplant

Outcome Measure Data

Analysis Population Description

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.

Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm	B - Cyclosporine (AC) Arm
Arm/Group Description	TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy	Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.
Measure Participants	38	39
2 weeks	72	1
1 month	204	6
3 months	334	54
6 months	429	158
12 months	485	243
24 months	434	502

Adverse Events

Time Frame	103 months and 22 days
Adverse Event Reporting Description	One participant was enrolled and given induction chemotherapy but was never randomized to Arm TMS or AC. Subject had one AE (infection with normal ANC or Grade 1 or 2 neutrophils: Pharynx). Subject was taken off study for disease progression and died.
Arm/Group Title	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm		B - Cyclosporine (AC) Arm
Arm/Group Description	TMS Arm Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg , start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy		AC Arm Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease Cyclosporine: Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy EPOCH-F: Fludarabine:25 mg/m2 per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m2 per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m2/d
All Cause Mortality
	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm		B - Cyclosporine (AC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/44 (18.2%)		19/45 (42.2%)
Serious Adverse Events
	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm		B - Cyclosporine (AC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/44 (81.8%)		41/45 (91.1%)
Blood and lymphatic system disorders
Edema: limb	1/44 (2.3%)	1	0/45 (0%)	0
Edema: viscera	1/44 (2.3%)	1	0/45 (0%)	0
Hemoglobin	3/44 (6.8%)	10	2/45 (4.4%)	4
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	0/44 (0%)	0	1/45 (2.2%)	1
Iron overload	0/44 (0%)	0	1/45 (2.2%)	1
Leukocytes (total WBC)	0/44 (0%)	0	2/45 (4.4%)	4
Lymphopenia	1/44 (2.3%)	1	2/45 (4.4%)	2
Neutrophils/granulocytes (ANC/AGC)	3/44 (6.8%)	4	1/45 (2.2%)	3
PTT (Partial Thromboplastin Time)	1/44 (2.3%)	1	0/45 (0%)	0
Platelets	1/44 (2.3%)	2	2/45 (4.4%)	11
Thrombotic microangiopathy	2/44 (4.5%)	2	1/45 (2.2%)	1
Cardiac disorders
Cardiac ischemia/infarction	1/44 (2.3%)	1	0/45 (0%)	0
Cardiopulmonary arrest, cause unknown (non-fatal)	1/44 (2.3%)	1	0/45 (0%)	0
Hypertension	0/44 (0%)	0	5/45 (11.1%)	5
Hypotension	3/44 (6.8%)	4	5/45 (11.1%)	6
Left ventricular diastolic dysfunction	1/44 (2.3%)	1	1/45 (2.2%)	1
Left ventricular systolic dysfunction	2/44 (4.5%)	3	4/45 (8.9%)	4
Right ventricular dysfunction (cor pulmonale)	0/44 (0%)	0	1/45 (2.2%)	1
Supraventricular and nodal arrhythmia::Atrial fibrillation	3/44 (6.8%)	5	0/45 (0%)	0
Supraventricular and nodal arrhythmia::Sinus tachycardia	0/44 (0%)	0	2/45 (4.4%)	2
Supraventricular and nodal arrhythmia::Supraventricular tachycardia	0/44 (0%)	0	1/45 (2.2%)	1
Ventricular arrhythmia::Ventricular tachycardia	0/44 (0%)	0	1/45 (2.2%)	1
Endocrine disorders
Adrenal insufficiency	0/44 (0%)	0	1/45 (2.2%)	1
Pancreatic endocrine: glucose intolerance	2/44 (4.5%)	2	1/45 (2.2%)	1
Eye disorders
Dry eye syndrome	3/44 (6.8%)	3	0/45 (0%)	0
Ocular/Visual - Other	0/44 (0%)	0	1/45 (2.2%)	1
Gastrointestinal disorders
Colitis	0/44 (0%)	0	1/45 (2.2%)	1
Colitis, infectious (e.g., Clostridium difficile)	5/44 (11.4%)	8	7/45 (15.6%)	12
Diarrhea	8/44 (18.2%)	9	8/45 (17.8%)	10
Dysphagia (difficulty swallowing)	1/44 (2.3%)	1	2/45 (4.4%)	2
Esophagitis	0/44 (0%)	0	1/45 (2.2%)	1
Gastritis (including bile reflux gastritis)	2/44 (4.5%)	2	0/45 (0%)	0
Heartburn/dyspepsia	0/44 (0%)	0	1/45 (2.2%)	1
Hemorrhage, GI::Abdomen NOS	0/44 (0%)	0	1/45 (2.2%)	1
Hemorrhage, GI::Duodenum	0/44 (0%)	0	1/45 (2.2%)	1
Hemorrhage, GI::Lower GI NOS	0/44 (0%)	0	3/45 (6.7%)	3
Hemorrhage, GI::Rectum	0/44 (0%)	0	1/45 (2.2%)	1
Hemorrhage, GI::Upper GI NOS	0/44 (0%)	0	1/45 (2.2%)	1
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/44 (2.3%)	1	1/45 (2.2%)	1
Mucositis/stomatitis (clinical exam)::Oral cavity	3/44 (6.8%)	3	0/45 (0%)	0
Mucositis/stomatitis (functional/symptomatic)::Oral cavity	1/44 (2.3%)	1	0/45 (0%)	0
Nausea	1/44 (2.3%)	1	2/45 (4.4%)	2
Pain::Abdomen NOS	1/44 (2.3%)	1	0/45 (0%)	0
Perforation, GI::Small bowel NOS	1/44 (2.3%)	1	0/45 (0%)	0
Stricture/stenosis (including anastomotic), GI::Esophagus	1/44 (2.3%)	1	0/45 (0%)	0
Ulcer, GI::Duodenum	1/44 (2.3%)	1	0/45 (0%)	0
General disorders
Death not associated with CTCAE term::Death NOS	4/44 (9.1%)	4	7/45 (15.6%)	7
Death not associated with CTCAE term::Disease progression NOS	3/44 (6.8%)	3	10/45 (22.2%)	10
Death not associated with CTCAE term::Multi-organ failure	1/44 (2.3%)	1	2/45 (4.4%)	2
Fatigue (asthenia, lethargy, malaise)	0/44 (0%)	0	1/45 (2.2%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	2/44 (4.5%)	2	1/45 (2.2%)	1
Tumor lysis syndrome	0/44 (0%)	0	1/45 (2.2%)	1
Weight gain	0/44 (0%)	0	1/45 (2.2%)	1
Hepatobiliary disorders
Cholecystitis	1/44 (2.3%)	1	1/45 (2.2%)	1
Liver dysfunction/failure (clinical)	1/44 (2.3%)	1	0/45 (0%)	0
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	2/44 (4.5%)	2	0/45 (0%)	0
Cytokine release syndrome/acute infusion reaction	0/44 (0%)	0	1/45 (2.2%)	1
Infections and infestations
Febrile neutropenia	6/44 (13.6%)	7	6/45 (13.3%)	9
Infection:: Abdomen NOS	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Bladder (urinary)	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Blood	3/44 (6.8%)	3	8/45 (17.8%)	10
Infection::Catheter-related	1/44 (2.3%)	1	4/45 (8.9%)	5
Infection ::Lip/perioral	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Lung (pneumonia)	4/44 (9.1%)	6	3/45 (6.7%)	3
Infection::Meninges (meningitis)	1/44 (2.3%)	1	0/45 (0%)	0
Infection ::Muscle (infection myositis)	0/44 (0%)	0	1/45 (2.2%)	1
Infection::Nose	0/44 (0%)	0	1/45 (2.2%)	1
Infection::Rectum	1/44 (2.3%)	1	0/45 (0%)	0
Infection::Sinus	2/44 (4.5%)	2	2/45 (4.4%)	2
Infection ::Trachea	1/44 (2.3%)	1	0/45 (0%)	0
Infection::Upper airway NOS	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Urinary tract NOS	2/44 (4.5%)	2	1/45 (2.2%)	1
Infection - Other	1/44 (2.3%)	3	2/45 (4.4%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)	1/44 (2.3%)	1	1/45 (2.2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood	9/44 (20.5%)	15	21/45 (46.7%)	40
Infection with normal ANC or Grade 1 or 2 neutrophils::Brain (encephalitis, infectious)	3/44 (6.8%)	3	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus	2/44 (4.5%)	3	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related	4/44 (9.1%)	4	12/45 (26.7%)	14
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Esophagus	1/44 (2.3%)	1	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Heart (endocarditis)	1/44 (2.3%)	1	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Liver	1/44 (2.3%)	1	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)	10/44 (22.7%)	18	13/45 (28.9%)	30
Infection with normal ANC or Grade 1 or 2 neutrophils::Meninges (meningitis)	1/44 (2.3%)	1	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal	1/44 (2.3%)	1	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx	2/44 (4.5%)	2	1/45 (2.2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus	4/44 (9.1%)	4	6/45 (13.3%)	8
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)	2/44 (4.5%)	3	4/45 (8.9%)	5
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS	1/44 (2.3%)	1	3/45 (6.7%)	4
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound	1/44 (2.3%)	1	1/45 (2.2%)	1
Infection with unknown ANC::Blood	2/44 (4.5%)	2	2/45 (4.4%)	2
Infection with unknown ANC::Catheter-related	1/44 (2.3%)	1	0/45 (0%)	0
Infection with unknown ANC::Colon	1/44 (2.3%)	1	0/45 (0%)	0
Infection with unknown ANC::Lung (pneumonia)	2/44 (4.5%)	2	1/45 (2.2%)	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	4/44 (9.1%)	5	1/45 (2.2%)	2
AST, SGOT(serum glutamic oxaloacetic transaminase)	4/44 (9.1%)	6	1/45 (2.2%)	2
Albumin, serum-low (hypoalbuminemia)	1/44 (2.3%)	1	1/45 (2.2%)	1
Alkaline phosphatase	1/44 (2.3%)	1	0/45 (0%)	0
Bilirubin (hyperbilirubinemia)	3/44 (6.8%)	3	2/45 (4.4%)	2
Creatinine	3/44 (6.8%)	5	2/45 (4.4%)	3
Magnesium, serum-low (hypomagnesemia)	0/44 (0%)	0	1/45 (2.2%)	1
Phosphate, serum-low (hypophosphatemia)	1/44 (2.3%)	2	1/45 (2.2%)	1
Potassium, serum-high (hyperkalemia)	0/44 (0%)	0	1/45 (2.2%)	1
Potassium, serum-low (hypokalemia)	0/44 (0%)	0	1/45 (2.2%)	1
Sodium, serum-low (hyponatremia)	1/44 (2.3%)	1	0/45 (0%)	0
Uric acid, serum-high (hyperuricemia)	0/44 (0%)	0	1/45 (2.2%)	1
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/44 (2.3%)	1	0/45 (0%)	0
Muscle weakness, generalized or specific area (not due to neuropathy)::Right-sided	0/44 (0%)	0	1/45 (2.2%)	1
Musculoskeletal/Soft Tissue - Other	0/44 (0%)	0	1/45 (2.2%)	1
Myositis (inflammation/damage of muscle)	0/44 (0%)	0	2/45 (4.4%)	2
Pain::Back	0/44 (0%)	0	1/45 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment (AML);	0/44 (0%)	0	4/45 (8.9%)	5
Secondary Malignancy - possibly related to cancer treatment (metastat. test cancer in lung)	1/44 (2.3%)	1	0/45 (0%)	0
Nervous system disorders
Ataxia (incoordination)	0/44 (0%)	0	1/45 (2.2%)	1
CNS cerebrovascular ischemia	0/44 (0%)	0	1/45 (2.2%)	1
Cognitive disturbance	0/44 (0%)	0	1/45 (2.2%)	1
Confusion	1/44 (2.3%)	1	1/45 (2.2%)	1
Encephalopathy	0/44 (0%)	0	3/45 (6.7%)	3
Hemorrhage, CNS	0/44 (0%)	0	2/45 (4.4%)	2
Leukoencephalopathy (radiographic findings)	0/44 (0%)	0	1/45 (2.2%)	1
Seizure	0/44 (0%)	0	1/45 (2.2%)	1
Somnolence/depressed level of consciousness	0/44 (0%)	0	1/45 (2.2%)	1
Renal and urinary disorders
Cystitis	1/44 (2.3%)	1	0/45 (0%)	0
Renal failure	10/44 (22.7%)	12	6/45 (13.3%)	10
Renal/Genitourinary - Other (AKI, required CVVH)	0/44 (0%)	0	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	0/44 (0%)	0	5/45 (11.1%)	6
Carbon monoxide diffusion capacity (DL(co))	0/44 (0%)	0	1/45 (2.2%)	1
Dyspnea (shortness of breath)	4/44 (9.1%)	5	3/45 (6.7%)	3
Hemorrhage, pulmonary/upper respiratory::Lung	1/44 (2.3%)	1	1/45 (2.2%)	1
Hemorrhage, pulmonary/upper respiratory::Nose	0/44 (0%)	0	1/45 (2.2%)	1
Hypoxia	7/44 (15.9%)	10	8/45 (17.8%)	13
Pericardial effusion (non-malignant)	2/44 (4.5%)	2	0/45 (0%)	0
Pleural effusion (non-malignant)	2/44 (4.5%)	2	2/45 (4.4%)	2
Pneumonitis/pulmonary infiltrates	2/44 (4.5%)	3	5/45 (11.1%)	5
Pulmonary/Upper Respiratory - Other (Specify, respiratory failure)	1/44 (2.3%)	1	0/45 (0%)	0
Pulmonary/Upper Respiratory - Other (pleural thickening)	0/44 (0%)	0	1/45 (2.2%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Deep sclerosis per MRI, GVHD possible)	1/44 (2.3%)	1	0/45 (0%)	0
Rash/desquamation	4/44 (9.1%)	5	7/45 (15.6%)	10
Rash: hand-foot skin reaction	1/44 (2.3%)	1	0/45 (0%)	0
Vascular disorders
Thrombosis/embolism (vascular access-related)	2/44 (4.5%)	2	0/45 (0%)	0
Thrombosis/thrombus/embolism	4/44 (9.1%)	5	1/45 (2.2%)	1
Other (Not Including Serious) Adverse Events
	A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm		B - Cyclosporine (AC) Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/44 (97.7%)		42/45 (93.3%)
Blood and lymphatic system disorders
Edema: head and neck	0/44 (0%)	0	1/45 (2.2%)	1
Edema: limb	1/44 (2.3%)	1	1/45 (2.2%)	1
Fibrinogen	1/44 (2.3%)	1	0/45 (0%)	0
Hemoglobin	26/44 (59.1%)	108	26/45 (57.8%)	150
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	1/44 (2.3%)	1	3/45 (6.7%)	4
Iron overload	1/44 (2.3%)	1	0/45 (0%)	0
Leukocytes (total WBC)	27/44 (61.4%)	118	26/45 (57.8%)	189
Lymphopenia	27/44 (61.4%)	143	27/45 (60%)	181
Neutrophils/granulocytes (ANC/AGC)	26/44 (59.1%)	109	27/45 (60%)	123
PTT (Partial Thromboplastin Time)	5/44 (11.4%)	5	8/45 (17.8%)	15
Platelets	25/44 (56.8%)	81	23/45 (51.1%)	106
Thrombotic microangiopathy	0/44 (0%)	0	4/45 (8.9%)	4
Cardiac disorders
Cardiac General - Other (cardimyopathy)	1/44 (2.3%)	1	0/45 (0%)	0
Cardiac General - Other (heart failure, fluid overload)	1/44 (2.3%)	1	0/45 (0%)	0
Cardiac ischemia/infarction	0/44 (0%)	0	1/45 (2.2%)	1
Hypertension	3/44 (6.8%)	3	7/45 (15.6%)	7
Hypotension	2/44 (4.5%)	2	3/45 (6.7%)	4
Left ventricular systolic dysfunction	1/44 (2.3%)	1	1/45 (2.2%)	1
Myocarditis	1/44 (2.3%)	1	0/45 (0%)	0
Pericardial effusion (non-malignant)	2/44 (4.5%)	2	1/45 (2.2%)	1
Pericarditis	0/44 (0%)	0	1/45 (2.2%)	1
Prolonged QTc interval	1/44 (2.3%)	1	1/45 (2.2%)	1
Supraventricular and nodal arrhythmia::Atrial fibrillation	1/44 (2.3%)	1	0/45 (0%)	0
Supraventricular and nodal arrhythmia::Sinus tachycardia	1/44 (2.3%)	1	0/45 (0%)	0
Congenital, familial and genetic disorders
Right ventricular dysfunction (cor pulmonale)	0/44 (0%)	0	1/45 (2.2%)	1
Endocrine disorders
Adrenal insufficiency	1/44 (2.3%)	1	1/45 (2.2%)	1
Pancreatic endocrine: glucose intolerance	3/44 (6.8%)	3	1/45 (2.2%)	1
Thyroid function, low (hypothyroidism)	0/44 (0%)	0	1/45 (2.2%)	1
Eye disorders
Dry eye syndrome	8/44 (18.2%)	8	2/45 (4.4%)	2
Ophthalmoplegia/diplopia (double vision)	1/44 (2.3%)	1	0/45 (0%)	0
Gastrointestinal disorders
Anorexia	2/44 (4.5%)	2	2/45 (4.4%)	4
Colitis	1/44 (2.3%)	1	3/45 (6.7%)	3
Colitis, infectious (e.g., Clostridium difficile)	1/44 (2.3%)	1	2/45 (4.4%)	2
Diarrhea	20/44 (45.5%)	25	22/45 (48.9%)	32
Dry mouth/salivary gland (xerostomia)	4/44 (9.1%)	4	1/45 (2.2%)	1
Dysphagia (difficulty swallowing)	3/44 (6.8%)	4	1/45 (2.2%)	2
Esophagitis	1/44 (2.3%)	1	0/45 (0%)	0
Fistula, GI::Anus	1/44 (2.3%)	1	0/45 (0%)	0
Gastritis (including bile reflux gastritis)	3/44 (6.8%)	3	0/45 (0%)	0
Gastrointestinal - Other (GVHD)	2/44 (4.5%)	2	0/45 (0%)	0
Gastrointestinal - Other	0/44 (0%)	0	1/45 (2.2%)	1
Heartburn/dyspepsia	3/44 (6.8%)	3	0/45 (0%)	0
Hemorrhage, GI::Abdomen NOS	1/44 (2.3%)	1	0/45 (0%)	0
Hemorrhage, GI::Anus	1/44 (2.3%)	1	0/45 (0%)	0
Hemorrhage, GI::Lower GI NOS	1/44 (2.3%)	3	0/45 (0%)	0
Mucositis/stomatitis (clinical exam)::Oral cavity	10/44 (22.7%)	10	0/45 (0%)	0
Mucositis/stomatitis (functional/symptomatic)::Oral cavity	8/44 (18.2%)	8	2/45 (4.4%)	2
Nausea	16/44 (36.4%)	17	6/45 (13.3%)	7
Pain::Anus	2/44 (4.5%)	2	0/45 (0%)	0
Pain::Throat/pharynx/larynx	1/44 (2.3%)	1	0/45 (0%)	0
Perforation, GI::Small bowel NOS	1/44 (2.3%)	1	0/45 (0%)	0
Taste alteration (dysgeusia)	0/44 (0%)	0	1/45 (2.2%)	1
Vomiting	2/44 (4.5%)	2	0/45 (0%)	0
General disorders
Fatigue (asthenia, lethargy, malaise)	2/44 (4.5%)	2	5/45 (11.1%)	5
Insomnia	1/44 (2.3%)	1	0/45 (0%)	0
Rigors/chills	0/44 (0%)	0	1/45 (2.2%)	1
Syndromes - Other (septic shock)	0/44 (0%)	0	1/45 (2.2%)	1
Weight loss	1/44 (2.3%)	1	0/45 (0%)	0
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	0/44 (0%)	0	1/45 (2.2%)	1
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/44 (2.3%)	1	0/45 (0%)	0
Infections and infestations
Febrile neutropenia	4/44 (9.1%)	4	9/45 (20%)	9
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/44 (6.8%)	3	9/45 (20%)	12
Infection	0/44 (0%)	0	1/45 (2.2%)	2
Infection ::Bladder (urinary)	6/44 (13.6%)	6	3/45 (6.7%)	3
Infection::Blood	9/44 (20.5%)	12	11/45 (24.4%)	14
Infection::Brain (encephalitis, infectious)	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Brain + Spinal cord (encephalomyelitis)	0/44 (0%)	0	1/45 (2.2%)	1
Infection::Bronchus	2/44 (4.5%)	2	1/45 (2.2%)	1
Infection ::Catheter-related	1/44 (2.3%)	1	0/45 (0%)	0
Infection ::Colon	2/44 (4.5%)	2	3/45 (6.7%)	3
Infection ::Eye NOS	1/44 (2.3%)	1	0/45 (0%)	0
Infection ::Lip/perioral	0/44 (0%)	0	1/45 (2.2%)	1
Infection ::Lung (pneumonia)	6/44 (13.6%)	8	6/45 (13.3%)	6
Infection::Oral cavity-gums (gingivitis)	0/44 (0%)	0	1/45 (2.2%)	1
Infection Sinus	2/44 (4.5%)	2	1/45 (2.2%)	1
Infection::Skin (cellulites)	1/44 (2.3%)	1	0/45 (0%)	0
Infection::Soft tissue NOS	1/44 (2.3%)	1	0/45 (0%)	0
Infection ::Upper aerodigestive NOS	1/44 (2.3%)	1	1/45 (2.2%)	1
Infection:: Upper airway NOS	1/44 (2.3%)	1	0/45 (0%)	0
Infection::Urinary tract NOS	2/44 (4.5%)	2	0/45 (0%)	0
Infection ::Wound	0/44 (0%)	0	1/45 (2.2%)	1
Infection - Other (CMV reactivation)	0/44 (0%)	0	1/45 (2.2%)	1
Infection - Other (Rhinovirus, Coronavirus HKU1)	0/44 (0%)	0	1/45 (2.2%)	1
Infection - Other (Varicella zoster; noravirus)	2/44 (4.5%)	2	0/45 (0%)	0
Infection - Other (acinetobacter)	0/44 (0%)	0	1/45 (2.2%)	1
Infection - Other (dissiminated HSV)	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)	3/44 (6.8%)	3	4/45 (8.9%)	5
Infection with normal ANC or Grade 1 or 2 neutrophils::Blood	20/44 (45.5%)	44	25/45 (55.6%)	62
Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus	1/44 (2.3%)	1	3/45 (6.7%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related	0/44 (0%)	0	2/45 (4.4%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Colon	2/44 (4.5%)	2	2/45 (4.4%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils::Conjunctiva	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)	7/44 (15.9%)	8	12/45 (26.7%)	18
Infection with normal ANC or Grade 1 or 2 neutrophils::Nose	2/44 (4.5%)	3	1/45 (2.2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal	0/44 (0%)	0	2/45 (4.4%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils::Penis	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx	2/44 (4.5%)	2	3/45 (6.7%)	5
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus	4/44 (9.1%)	6	9/45 (20%)	10
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)	2/44 (4.5%)	2	3/45 (6.7%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach	1/44 (2.3%)	1	0/45 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils::Trachea	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper aerodigestive NOS	1/44 (2.3%)	1	2/45 (4.4%)	3
Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS	9/44 (20.5%)	14	9/45 (20%)	10
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS	4/44 (9.1%)	4	5/45 (11.1%)	6
Infection with normal ANC or Grade 1 or 2 neutrophils::Vagina	0/44 (0%)	0	1/45 (2.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils::Wound	0/44 (0%)	0	3/45 (6.7%)	4
Infection with unknown ANC::Blood	4/44 (9.1%)	4	2/45 (4.4%)	3
Infection with unknown ANC::Bronchus	0/44 (0%)	0	1/45 (2.2%)	1
Infection with unknown ANC::Catheter-related	0/44 (0%)	0	1/45 (2.2%)	1
Infection with unknown ANC::Lung (pneumonia)	1/44 (2.3%)	1	1/45 (2.2%)	1
Infection with unknown ANC::Sinus	1/44 (2.3%)	1	0/45 (0%)	0
Infection with unknown ANC::Skin (cellulites)	0/44 (0%)	0	1/45 (2.2%)	1
Infection with unknown ANC::Upper aerodigestive NOS	0/44 (0%)	0	1/45 (2.2%)	1
Infection with unknown ANC::Upper airway NOS	6/44 (13.6%)	7	2/45 (4.4%)	2
Infection with unknown ANC::Urinary tract NOS	1/44 (2.3%)	1	0/45 (0%)	0
Infection with unknown ANC::Wound	1/44 (2.3%)	1	0/45 (0%)	0
Opportunistic infection associated with >=Grade 2 Lymphopenia	0/44 (0%)	0	1/45 (2.2%)	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	28/44 (63.6%)	75	17/45 (37.8%)	45
AST, SGOT(serum glutamic oxaloacetic transaminase)	26/44 (59.1%)	73	23/45 (51.1%)	50
Acidosis (metabolic or respiratory)	0/44 (0%)	0	1/45 (2.2%)	1
Albumin, serum-low (hypoalbuminemia)	9/44 (20.5%)	15	12/45 (26.7%)	23
Alkaline phosphatase	7/44 (15.9%)	20	6/45 (13.3%)	9
Alkalosis (metabolic or respiratory)	1/44 (2.3%)	1	0/45 (0%)	0
Amylase	1/44 (2.3%)	1	1/45 (2.2%)	1
Bicarbonate, serum-low	1/44 (2.3%)	1	2/45 (4.4%)	2
Bilirubin (hyperbilirubinemia)	12/44 (27.3%)	22	16/45 (35.6%)	38
CPK (creatine phosphokinase)	1/44 (2.3%)	4	1/45 (2.2%)	1
Calcium, serum-high (hypercalcemia)	0/44 (0%)	0	2/45 (4.4%)	2
Calcium, serum-low (hypocalcemia)	0/44 (0%)	0	2/45 (4.4%)	2
Creatinine	9/44 (20.5%)	11	10/45 (22.2%)	16
GGT (gamma-Glutamyl transpeptidase)	3/44 (6.8%)	4	3/45 (6.7%)	3
Glucose, serum-high (hyperglycemia)	1/44 (2.3%)	1	0/45 (0%)	0
Lipase	1/44 (2.3%)	1	0/45 (0%)	0
Magnesium, serum-high (hypermagnesemia)	13/44 (29.5%)	22	16/45 (35.6%)	26
Magnesium, serum-low (hypomagnesemia)	3/44 (6.8%)	4	9/45 (20%)	15
Metabolic/Laboratory - Other (pancytopenia; steroid induced hyperglycemia)	2/44 (4.5%)	2	0/45 (0%)	0
Phosphate, serum-low (hypophosphatemia)	20/44 (45.5%)	69	22/45 (48.9%)	53
Potassium, serum-high (hyperkalemia)	3/44 (6.8%)	3	10/45 (22.2%)	15
Potassium, serum-low (hypokalemia)	10/44 (22.7%)	16	17/45 (37.8%)	36
Sodium, serum-high (hypernatremia)	1/44 (2.3%)	1	1/45 (2.2%)	1
Sodium, serum-low (hyponatremia)	6/44 (13.6%)	9	9/45 (20%)	11
Triglyceride, serum-high (hypertriglyceridemia)	1/44 (2.3%)	1	0/45 (0%)	0
Uric acid, serum-high (hyperuricemia)	4/44 (9.1%)	5	7/45 (15.6%)	16
Musculoskeletal and connective tissue disorders
Joint-function	1/44 (2.3%)	1	0/45 (0%)	0
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-lower	0/44 (0%)	0	1/45 (2.2%)	1
Osteonecrosis (avascular necrosis)	1/44 (2.3%)	1	0/45 (0%)	0
Pain::Back	1/44 (2.3%)	1	1/45 (2.2%)	1
Pain::Joint	0/44 (0%)	0	1/45 (2.2%)	1
Pain::Muscle	2/44 (4.5%)	2	0/45 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment (mucoepidermoid carcinoma)	1/44 (2.3%)	1	0/45 (0%)	0
Secondary Malignancy - possibly related to cancer treatment (squamous cell carcinoma lip)	1/44 (2.3%)	1	0/45 (0%)	0
Nervous system disorders
Confusion	0/44 (0%)	0	1/45 (2.2%)	2
Dizziness	0/44 (0%)	0	1/45 (2.2%)	1
Encephalopathy	1/44 (2.3%)	1	0/45 (0%)	0
Leukoencephalopathy (radiographic findings)	0/44 (0%)	0	1/45 (2.2%)	1
Memory impairment	1/44 (2.3%)	1	0/45 (0%)	0
Mood alteration::Anxiety	2/44 (4.5%)	2	2/45 (4.4%)	2
Mood alteration::Depression	1/44 (2.3%)	1	3/45 (6.7%)	3
Neurology - Other (delirium)	0/44 (0%)	0	1/45 (2.2%)	1
Neuropathy: motor	2/44 (4.5%)	2	2/45 (4.4%)	2
Neuropathy: sensory	4/44 (9.1%)	4	1/45 (2.2%)	1
Pain::Head/headache	2/44 (4.5%)	2	2/45 (4.4%)	2
Psychosis (hallucinations/delusions)	1/44 (2.3%)	1	0/45 (0%)	0
Seizure	0/44 (0%)	0	1/45 (2.2%)	1
Syncope (fainting)	0/44 (0%)	0	1/45 (2.2%)	1
Renal and urinary disorders
Cystitis	1/44 (2.3%)	1	1/45 (2.2%)	1
Hemorrhage, GU::Bladder	3/44 (6.8%)	3	0/45 (0%)	0
Hemorrhage, GU::Urinary NOS	0/44 (0%)	0	1/45 (2.2%)	1
Obstruction, GU::Bladder	0/44 (0%)	0	1/45 (2.2%)	1
Pain::Urethra	1/44 (2.3%)	1	0/45 (0%)	0
Renal failure	4/44 (9.1%)	5	4/45 (8.9%)	4
Renal/Genitourinary - Other (acute renal injury)	3/44 (6.8%)	4	0/45 (0%)	0
Renal/Genitourinary - Other (dysuria)	1/44 (2.3%)	1	0/45 (0%)	0
Renal/Genitourinary - Other (dysuria; hematuria; stent replacement)	1/44 (2.3%)	1	0/45 (0%)	0
Renal/Genitourinary - Other (failure; hematuria; insufficiency; dysuria)	0/44 (0%)	0	6/45 (13.3%)	7
Renal/Genitourinary - Other (fluid overload refractory to normal doses of Lasix)	1/44 (2.3%)	1	0/45 (0%)	0
Renal/Genitourinary - Other (hematuria)	1/44 (2.3%)	1	0/45 (0%)	0
Renal/Genitourinary - Other (insufficiency)	4/44 (9.1%)	4	0/45 (0%)	0
Urinary frequency/urgency	1/44 (2.3%)	1	0/45 (0%)	0
Urinary retention (including neurogenic bladder)	1/44 (2.3%)	1	0/45 (0%)	0
Reproductive system and breast disorders
Vaginal dryness	2/44 (4.5%)	2	2/45 (4.4%)	2
Vaginal mucositis	1/44 (2.3%)	1	0/45 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/44 (2.3%)	1	1/45 (2.2%)	1
Bronchospasm, wheezing	1/44 (2.3%)	1	1/45 (2.2%)	1
Carbon monoxide diffusion capacity (DL(co))	3/44 (6.8%)	3	5/45 (11.1%)	5
Cough	1/44 (2.3%)	1	0/45 (0%)	0
Dyspnea (shortness of breath)	4/44 (9.1%)	5	3/45 (6.7%)	3
FEV(1)	2/44 (4.5%)	3	1/45 (2.2%)	1
Hiccoughs (hiccups, singultus)	0/44 (0%)	0	2/45 (4.4%)	2
Hypoxia	5/44 (11.4%)	5	4/45 (8.9%)	8
Pleural effusion (non-malignant)	3/44 (6.8%)	3	2/45 (4.4%)	2
Pneumonitis/pulmonary infiltrates	1/44 (2.3%)	1	1/45 (2.2%)	1
Pneumothorax	0/44 (0%)	0	1/45 (2.2%)	1
Pulmonary/Upper Respiratory - Other (infiltrates)	0/44 (0%)	0	1/45 (2.2%)	2
Pulmonary/Upper Respiratory - Other (infiltrates; fungal pneumonia)	1/44 (2.3%)	1	0/45 (0%)	0
Skin breakdown/decubitus ulcer	1/44 (2.3%)	1	1/45 (2.2%)	1
Wound complication, non-infectious	0/44 (0%)	0	1/45 (2.2%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (GVHD; cGVHD)	2/44 (4.5%)	2	0/45 (0%)	0
Dermatology/Skin - Other (MRSA abscess)	0/44 (0%)	0	1/45 (2.2%)	1
Dry skin	1/44 (2.3%)	1	1/45 (2.2%)	1
Hyperpigmentation	4/44 (9.1%)	5	0/45 (0%)	0
Induration/fibrosis (skin and subcutaneous tissue)	4/44 (9.1%)	5	0/45 (0%)	0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	0/44 (0%)	0	1/45 (2.2%)	1
Pruritus/itching	0/44 (0%)	0	2/45 (4.4%)	2
Rash/desquamation	19/44 (43.2%)	30	26/45 (57.8%)	39
Rash: acne/acneiform	3/44 (6.8%)	3	1/45 (2.2%)	1
Rash: hand-foot skin reaction	0/44 (0%)	0	1/45 (2.2%)	1
Ulceration	2/44 (4.5%)	2	2/45 (4.4%)	2
Vascular disorders
Phlebitis (including superficial thrombosis)	1/44 (2.3%)	1	0/45 (0%)	0
Thrombosis/embolism (vascular access-related)	1/44 (2.3%)	1	2/45 (4.4%)	2
Thrombosis/thrombus/embolism	6/44 (13.6%)	6	2/45 (4.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.