TBI Dose De-escalation for Fanconi Anemia

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00352976
• Collaborator: (none)
• Enrollment: 83
• Location: 1
• Arm: 1
• Actual Duration (Months): 172.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a single arm, total body irradiation (TBI) trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.

Condition or Disease	Intervention/Treatment	Phase
Fanconi Anemia	Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Total Body Irradiation; Procedure: Bone Marrow Transplantation; Drug: Mycophenolate Mofetil; Drug: Sirolimus	Phase 2/Phase 3

Detailed Description

Study Treatment: Patients will receive voriconazole (antifungal therapy) by mouth beginning 1 month prior to conditioning therapy, if possible. 1) The subject is to receive total body irradiation (300 cGy) with thymic shielding; it will be given six days before the stem cells are given (day -6). 2) Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine and Cyclophosphamide via central line (i.e. Hickman or Broviac). Starting Day -3, patients will receive sirolimus therapy with a taper commencing on day +180 and also mycophenolate mofetil (MMF) through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). 4) If the subject is receiving bone marrow or "peripheral" stem cells (cells collected from the donor's arm via a cell separator), on the day of transplantation, the stem cells taken from the donor will be put into a machine which will separate the lymphocytes (the cells that cause graft-versus-host disease [GVHD]) from the stem cells. If the subject is receiving an umbilical cord blood, the lymphocytes will not be removed because the risk of GVHD is not as high. Otherwise all patients will receive the same treatment. The stem cells are given as an infusion into the subject's existing catheter over 1-2 hours on day 0.5. On the day after transplant (day +1) subjects will be given G-CSF to stimulate the growth of the transplanted cells. 6. While receiving treatment and until the subject's blood counts recover he/she will have daily blood tests, and several bone marrow biopsies and aspirates. After recovery, subjects will be seen once a month for a health assessment and blood tests until at least 3 months after the cells have been infused. Additional blood tests or assessments may be done as medically indicated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation
• Actual Study Start Date: May 18, 2006
• Actual Primary Completion Date: Oct 9, 2020
• Actual Study Completion Date: Oct 9, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment with TBI Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.

Drug: Cyclophosphamide; Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac),10 mg/kg intravenously (IV); Other Names: cytoxan ; Drug: Fludarabine; Day -5 through Day -2 prior to transplant; subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac),35 mg/m^2 intravenous (IV); Other Names: fludara ; Procedure: Total Body Irradiation; total body irradiation (300 cGy) with thymic shielding will be given six days before the stem cells are given (day -6). Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.; Other Names: Radiation Therapy, Therapeutic radiation ; Procedure: Bone Marrow Transplantation; A target of 5 * 10^6/kg and a minimum of 4 * 10^6 CD34+ cell/kg recipient weight will be collected by apheresis and used for transplant. In most cases this dose will be recovered in a single apheresis; however, a second or rarely third apheresis performed on the following days may be required to achieve the minimum dose.; Other Names: Stem Cell transplantation ; Drug: Mycophenolate Mofetil; Patients will receive MMF therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 * 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours by mouth(to a maximum dose of 1 gram).; Other Names: MMF ; Drug: Sirolimus; Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC). Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation.; Other Names: Rapamycin

Outcome Measures

Primary Outcome Measures

1. Number of Participant With Neutrophil Recovery [by day 42]

   Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days

Secondary Outcome Measures

1. Number of Participants Experiencing Grade ≥3 Regimen Related Toxicity [by day 100]

   Regimen related toxicities (RRT) include: significant hemorrhagic cystitis, pulmonary hemorrhage, interstitial pneumonitis, GI hemorrhage, renal failure, erythroderma, and severe hepatic veno-occlusive disease

2. Number of Participants With Secondary Graft Failure at 100 Days [100 days]

   Secondary Graft Rejection by day 100

3. Number of Participants Experiencing Acute Graft-versus-host Disease (GVHD) [at 100 days]

   Number of participants experiencing acute GVHD (all grades) by day 100

4. Number of Participants Experiencing Chronic GVHD [at one year]

   Number of participants experiencing chronic Graft Vs Host Disease by 1 year

5. Number of Participants Experiencing Overall Survival [at one year]

   Number of participants experiencing overall survival by 1 year

6. Number of Participants Experiencing Infections by Day 100 [by day 100]

7. Number of Participants Experiencing Infections by Day 180 [by day 180]

8. Number of Participants Experiencing Infections by Day 365 [by day 365]

9. Average Immunoglobulin G (IgG) Levels as a Measure of Immune Reconstitution After Transplant, by 100 Days [by 100 days]

10. Average IgG Levels as a Measure of Immune Reconstitution After Transplant, by 180 Days [by 180 days]

11. Average IgG Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [by 365 days]

12. Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 100 Days [by 100 days]

13. Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 180 Days [by 180 days]

14. Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [by 365 days]

15. Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 100 Days [by 100 days]

16. Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 180 Days [by 180 days]

17. Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [by 365 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Meeting the definition of standard risk or high risk Fanconi anemia as defined in the next two sections:

• Standard risk patients must be <18 years of age with a diagnosis of Fanconi anemia with aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below:

• Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:

• platelet count <20 * 10^9/L

• ANC <5 * 10^8/L

• Hemoglobin <8 g/dL

• Myelodysplastic syndrome (MDS) with multilineage dysplasia with or without chromosomal anomalies

• High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)

• High risk patients must have one or more of the following high risk features:

• Advanced MDS (≥ 5% blast) or acute leukemia

• Require additional HSCT for graft failure

• History at any time of systemic fungal or gram negative infection

• Severe renal disease with a creatinine clearance <40 mL/min

• Age > 18 years

• Very high risk patients must have Advanced MDS (≥ 5% blast) or acute leukemia after initial hematopoietic stem cell transplant (HSCT)

• Patients must have an appropriate source of stem cells. Patients and donors will be typed for HLA-A, B, C and DRB1 using high resolution molecular typing.

• Adequate major organ function including:

• Cardiac: ejection fraction >45%

• Hepatic: bilirubin, AST or ALT, ALP <5 x normal

• Karnofsky performance status >70% or Lansky >50 (if < 16 years of age)

• Women of child-bearing age must be using adequate birth control and have a negative pregnancy test.

• Written consent.

Exclusion Criteria:

• Available HLA-genotypically identical related donor in standard risk patients.

• Active central nervous system (CNS) leukemia at time of study enrollment.

• History of squamous cell carcinoma of the head/neck/cervix within previous 2 years.

• Prior radiation therapy that prevents further total body irradiation (TBI).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Margaret L MacMillan, M.D., University of Minnesota Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 16, 2018

More Information

Additional Information:

• Trial 4 listed in the article corresponds to this clinical trial.

Publications

• MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00352976
• Other Study ID Numbers: MT2006-05; 0605M85788
• First Posted: Jul 17, 2006
• Last Update Posted: Nov 24, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Masonic Cancer Center, University of Minnesota: Bone Marrow transplant; stem cell transplant; cord blood transplant; total body irradiation; thymic shielding
• Additional relevant MeSH terms: Fanconi Syndrome; Anemia; Fanconi Anemia; Mycophenolic Acid; Sirolimus; Cyclophosphamide; Fludarabine

Study Results

Participant Flow

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation 300 cGy, Fludarabine 35 mg/m^2 (over 30 minutes daily for 4 days for a total dose of 140 mg/m^2), Cyclophosphamide 10 mg/kg (2 hour infusion for 4 days for a total dose of 40 mg/kg), Bone Marrow Transplantation, Mycophenolate Mofetil 1 mg/kg(over 30 minutes every 12 hours for 5 days) , and Sirolimus.
Period Title: Overall Study
STARTED	83
COMPLETED	83
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Overall Participants	83
Age (Count of Participants)
<=18 years	68 81.9%
Between 18 and 65 years	15 18.1%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	36 43.4%
Male	47 56.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.2%
Not Hispanic or Latino	82 98.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	8 9.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 7.2%
White	66 79.5%
More than one race	3 3.6%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	80 96.4%
Argentina	1 1.2%
Canada	2 2.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participant With Neutrophil Recovery
Description	Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days
Time Frame	by day 42

Outcome Measure Data

Analysis Population Description

1 patient not evaluable since deceased at day 5 post transplant

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	82
Count of Participants [Participants]	78 94%

2. Secondary Outcome

Title	Number of Participants Experiencing Grade ≥3 Regimen Related Toxicity
Description	Regimen related toxicities (RRT) include: significant hemorrhagic cystitis, pulmonary hemorrhage, interstitial pneumonitis, GI hemorrhage, renal failure, erythroderma, and severe hepatic veno-occlusive disease
Time Frame	by day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	71 85.5%

3. Secondary Outcome

Title	Number of Participants With Secondary Graft Failure at 100 Days
Description	Secondary Graft Rejection by day 100
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	4 4.8%

4. Secondary Outcome

Title	Number of Participants Experiencing Acute Graft-versus-host Disease (GVHD)
Description	Number of participants experiencing acute GVHD (all grades) by day 100
Time Frame	at 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	15 18.1%

5. Secondary Outcome

Title	Number of Participants Experiencing Chronic GVHD
Description	Number of participants experiencing chronic Graft Vs Host Disease by 1 year
Time Frame	at one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	6 7.2%

6. Secondary Outcome

Title	Number of Participants Experiencing Overall Survival
Description	Number of participants experiencing overall survival by 1 year
Time Frame	at one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	70 84.3%

7. Secondary Outcome

Title	Number of Participants Experiencing Infections by Day 100
Time Frame	by day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	53 63.9%

8. Secondary Outcome

Title	Number of Participants Experiencing Infections by Day 180
Time Frame	by day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	55 66.3%

9. Secondary Outcome

Title	Number of Participants Experiencing Infections by Day 365
Time Frame	by day 365

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Count of Participants [Participants]	56 67.5%

10. Secondary Outcome

Title	Average Immunoglobulin G (IgG) Levels as a Measure of Immune Reconstitution After Transplant, by 100 Days
Time Frame	by 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Average IgG levels as a measure of immune reconstitution after transplant
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	550.6 (285.4)

11. Secondary Outcome

Title	Average IgG Levels as a Measure of Immune Reconstitution After Transplant, by 180 Days
Time Frame	by 180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	652.9 (305.8)

12. Secondary Outcome

Title	Average IgG Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
Time Frame	by 365 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	724.0 (258.0)

13. Secondary Outcome

Title	Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 100 Days
Time Frame	by 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	88.0 (59.9)

14. Secondary Outcome

Title	Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 180 Days
Time Frame	by 180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	98.7 (48.8)

15. Secondary Outcome

Title	Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
Time Frame	by 365 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	107.2 (57.0)

16. Secondary Outcome

Title	Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 100 Days
Time Frame	by 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	71.1 (84.2)

17. Secondary Outcome

Title	Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 180 Days
Time Frame	by 180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	77.0 (60.3)

18. Secondary Outcome

Title	Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
Time Frame	by 365 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
Measure Participants	83
Mean (Standard Deviation) [mg/dL]	82.8 (57.9)

Adverse Events

Time Frame	Through after transplant by 365 Days
Arm/Group Title	Treatment With TBI
Arm/Group Description	Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
All Cause Mortality
	Treatment With TBI
	Affected / at Risk (%)	# Events
Total	13/83 (15.7%)
Serious Adverse Events
	Treatment With TBI
	Affected / at Risk (%)	# Events
Total	4/83 (4.8%)
Blood and lymphatic system disorders
Progressive Disease	1/83 (1.2%)	3
Relapsed	1/83 (1.2%)	2
Blood/Bone Marrow GVHD	1/83 (1.2%)	1
Infections and infestations
Infection	2/83 (2.4%)	2
Injury, poisoning and procedural complications
Graft failure	1/83 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Treatment With TBI
	Affected / at Risk (%)	# Events
Total	75/83 (90.4%)
Blood and lymphatic system disorders
Anemia	1/83 (1.2%)	1
Injury, poisoning and procedural complications, other	1/83 (1.2%)	1
Investigations, other	1/83 (1.2%)	1
Thrombosis	3/83 (3.6%)	5
Thrombotic thrombocytopenic purpura	1/83 (1.2%)	1
hemolysis	1/83 (1.2%)	1
hypoatremia	1/83 (1.2%)	1
neurotoxicity	1/83 (1.2%)	1
Cardiac disorders
cardiomegaly	1/83 (1.2%)	1
Hemorrhage	1/83 (1.2%)	1
Pericardial Effusion	11/83 (13.3%)	13
atrial fibrilation	1/83 (1.2%)	1
cardiac arrest	1/83 (1.2%)	1
cardiomyopathy	1/83 (1.2%)	1
edema	1/83 (1.2%)	1
Ear and labyrinth disorders
myringotomy	1/83 (1.2%)	1
Gastrointestinal disorders
Hemorrhage	1/83 (1.2%)	3
Ileum obstruction	1/83 (1.2%)	1
Mucositis	4/83 (4.8%)	4
cholecystectomy	1/83 (1.2%)	1
hepatic steatosis	1/83 (1.2%)	1
hernia	1/83 (1.2%)	1
ischemic hepatitis	1/83 (1.2%)	1
pancreatic inflammation	1/83 (1.2%)	1
proximal obstruction	1/83 (1.2%)	1
General disorders
multi-system failure	3/83 (3.6%)	3
Hepatobiliary disorders
Hemmorhage	1/83 (1.2%)	1
Veno-Occlusive Disease	3/83 (3.6%)	4
Immune system disorders
allergic reaction	1/83 (1.2%)	1
Infections and infestations
Herpes	5/83 (6%)	6
Infection	42/83 (50.6%)	122
Sepsis	1/83 (1.2%)	1
Septic shock	1/83 (1.2%)	1
Injury, poisoning and procedural complications
Engraftment Syndrome	9/83 (10.8%)	9
GI bleed	13/83 (15.7%)	15
Injury, poisoning and procedural complications, other	2/83 (2.4%)	2
Investigations
Investigations, other	1/83 (1.2%)	1
Metabolism and nutrition disorders
Anorexia	2/83 (2.4%)	2
Type 2 Diabetes	1/83 (1.2%)	1
hyperglycemia	6/83 (7.2%)	6
Nervous system disorders
altered mental status	1/83 (1.2%)	1
intracranial hemorrhage	2/83 (2.4%)	2
neurotoxicity	2/83 (2.4%)	3
vision impairment	3/83 (3.6%)	3
Renal and urinary disorders
Acute kidney injury	2/83 (2.4%)	2
Cystitis	26/83 (31.3%)	30
Dialysis	6/83 (7.2%)	7
Injury, poisoning and procedural complications, other	1/83 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/83 (1.2%)	1
Adult respiratory distress syndrome	1/83 (1.2%)	1
Drug Toxicity	1/83 (1.2%)	1
Intubation	11/83 (13.3%)	14
Pneumonia	31/83 (37.3%)	74
Pulmonary Hemorrhage	7/83 (8.4%)	7
Respiratory failure	1/83 (1.2%)	1
Respirtory distress syndrome	1/83 (1.2%)	1
Sinusitis	7/83 (8.4%)	9
bilateral interstitial lung disease	1/83 (1.2%)	1
epistaxis	1/83 (1.2%)	2
pnuemothorax	1/83 (1.2%)	1
pulmonary cytolytic thrombi	1/83 (1.2%)	1
Skin and subcutaneous tissue disorders
Drug Toxicity	3/83 (3.6%)	3
Vascular disorders
Hypertension	24/83 (28.9%)	26
Neuropathy	1/83 (1.2%)	1
hypotension	1/83 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.