Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00800839
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if cyclophosphamide given after busulfan and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which transplanted tissue attacks the body into which it is transplanted) in patients receiving a stem cell transplant. The safety of this drug combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Diseases; Leukemia; Lymphoma; Myeloma	Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 2

Detailed Description

The Study Drugs:

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. It is also designed to suppress the immune system and help prevent GVHD.

Study Drug Administration and Transplant:

If you are an inpatient, on Day -8 (8 days before the date of transplant), you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour.

If you are an outpatient, on Day -30 through Day -8, you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour each day.

You will be given an anti-seizure drug to help prevent seizures each time you receive busulfan. Your doctor will explain how the drug will be given and the drug's risks. Seizures are a rare but serious side effect of busulfan.

On Days -8, -6, and -4, blood (about 1 teaspoon each time) will then be drawn a total of 11 times for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan.

On Day -6 through Day -3, you will receive your body-specific dose of busulfan by vein over 3 hours each day. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose. You will receive fludarabine through a needle in your vein over 1 hour on each of these days before you receive busulfan.

On Day 0, you will receive the donor bone marrow or blood stem cells by vein over about 1 hour.

On Day +3 and Day +4, you will receive cyclophosphamide by vein over 3 hours.

On Days +3 thru +5 just before the first dose of cyclophosphamide and then every 4 hours, you will receive mesna by vein over 30 minutes for a total of 10 doses. Mesna is a drug that protects bladder cells from damage by chemotherapy drugs. It is used to decrease the risk of bleeding in the bladder.

Once a day starting on Day +7, you will receive filgrastim (G-CSF -- a drug that helps with the growth of white blood cells) through a needle under your skin until your blood cell levels reach "recovered" levels for 3 days in a row.

Study Visits:

Every day you are in the hospital and at each outpatient visit, you will have a physical exam to check for symptoms of GVHD.

Blood (about 3 teaspoons) will be drawn at least 2 times a week for the first 100 days after the transplant for routine tests.

About 1 month after your transplant, then once every 3 months up to a year, the following tests and procedures will be performed:

• Blood (about 5 tablespoons) will be drawn for routine tests and to check for CMV. Blood draws may be repeated more often, if you doctor thinks it is needed.

• Urine will be collected for routine tests.

• You will have a bone marrow aspirate and biopsy to check the status of the disease.

At Months 1, 2, 3, 6, and 12 after your transplant, blood (about 4 tablespoons) will be drawn to check the status of your immune system.

Tests and procedures may be repeated more often during the study, if your doctor thinks it is needed.

Length of Study:

You will be on study in the hospital for about 4 weeks. You will be taken off study if the disease gets worse or if the study doctor thinks it is in your best interest.

Long-Term Follow-Up:

After the first 24 months, you will receive either a phone call or a letter from the study doctor or your regular doctor 1 time each year to check the status of the disease. If you are contacted by mail, you will be given a self-addressed stamped envelope with which you can return your responses to the doctor.

This is an investigational study. Busulfan is FDA approved and commercially available for the treatment of chronic myelogenous leukemia (CML). Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Cyclophosphamide is FDA approved and commercially available for the treatment of lymphoma. The use of these drugs together for the possible prevention of GVHD is investigational.

Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Busulfan (IV) and Fludarabine Followed by Post-allogeneic Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies.
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jul 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Busulfan + Fludarabine + Cyclophosphamide Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Drug: Busulfan; Starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.; Other Names: Bulsulfex™ Myleran® ; Drug: Fludarabine; Dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.; Other Names: Fludarabine Phosphate Fludara ; Drug: Cyclophosphamide; Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.; Other Names: Cytoxan® Neosar®

Outcome Measures

Primary Outcome Measures

1. Cumulative Incidence of Grade II to IV Acute GVHD [100 days post transplant]

   Graft Versus Host Disease (GVHD) defined as grade 2 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

2. Cumulative Incidence of Grade III to IV Acute GVHD [100 days post transplant]

   Graft Versus Host Disease (GVHD) defined as grade 3 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

3. Day-100 Treatment-Related Mortality [100 days post transplant]

   Treatment-Related Mortality (TRM) was estimated from the date of transplant using the cumulative incidence method to account for competing risks. Disease progression or relapse death were considered competing risk for TRM.

Secondary Outcome Measures

1. Rate of Engraftment [From engraftment to 60 days post transplant]

   Engraftment defined as the evidence of donor derived cells (more than 5%) by bone marrow chimerism studies in the presence of neutrophil recovery by day 28 post stem cell (SC) infusion. Engraftment date is the first day of three (3) consecutive days that the ANC exceeds 0.5 x109/L. Delayed engraftment is defined as the evidence of engraftment beyond day 28 post SC infusion achieved after the administration of therapeutic (high dose) hematopoietic growth factors.

2. 2-year Progression-Free Survival [First 25-35 days post transplant and then every 3 months for a maximum of 2 years]

   Progression-free survival (PFS) is defined as the interval between day of transplant and day of death or disease progression.

3. 2-year Overall Survival [First 25-35 days post transplant and then every 3 months for a maximum of 2 years]

   Overall Survival (OS) is defined as the interval between day of transplant and day of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with high risk hematological malignancies, including those with induction failure and after treated or untreated relapse.

2. HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority.

3. Age 6 months to 75 years.

4. Bilirubin </= 1.5 mg/dl, serum glutamate pyruvate transaminase (SGPT) </= 200 IU/ml (unless Gilbert's syndrome).

5. Calculated creatinine clearance of >50mL/min using the Cockcroft-Gault equation for adult patients 18 to 70 years old, and the Schwartz equation for pediatric patients 6 months to 17 years old.

6. Diffusing capacity for carbon monoxide (DLCO) >45% predicted corrected for hemoglobin (as reported by the Pulmonary Function Laboratory at MDACC). For most children </= 6 years of age who are unable to perform pulmonary function test (PFT), pulse oximetry

/= 92% on room air.

1. left ventricular ejection fraction (LVEF) >/= 35%.

Exclusion Criteria:

1. HIV seropositivity

2. Uncontrolled infections.

3. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization

4. Inability to sign consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Amin Alousi, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00800839
• Other Study ID Numbers: 2008-0261; NCI-2012-01660
• First Posted: Dec 2, 2008
• Last Update Posted: Sep 19, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Post-allogeneic transplantation; Graft-versus-Host Disease Prophylaxis; Graft-versus-Host Disease; GVHD; Hematologic malignancies; Leukemia; Lymphoma; Myeloma; Human Leukocyte Antigen; HLA; Busulfan; Cyclophosphamide; Fludarabine; Mesna; Cytoxan®; Neosar®; Busulfex; Myleran®; Fludarabine Phosphate
• Additional relevant MeSH terms: Hematologic Diseases; Vidarabine; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate

Study Results

Participant Flow

Recruitment Details	Recruitment Period: September 02, 2008 to December 12, 2011. All recruitment was done at The University of Texas (UT) MD Anderson Cancer Center.

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Period Title: Overall Study
STARTED	56
COMPLETED	49
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Overall Participants	49
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	21 42.9%
Male	28 57.1%
Region of Enrollment (participants) [Number]
United States	49 100%

Outcome Measures

1. Primary Outcome

Title	Cumulative Incidence of Grade II to IV Acute GVHD
Description	Graft Versus Host Disease (GVHD) defined as grade 2 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Number (95% Confidence Interval) [percentage of incidence]	53

2. Primary Outcome

Title	Cumulative Incidence of Grade III to IV Acute GVHD
Description	Graft Versus Host Disease (GVHD) defined as grade 3 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Number (95% Confidence Interval) [percentage of incidence]	22

3. Primary Outcome

Title	Day-100 Treatment-Related Mortality
Description	Treatment-Related Mortality (TRM) was estimated from the date of transplant using the cumulative incidence method to account for competing risks. Disease progression or relapse death were considered competing risk for TRM.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	14 28.6%

4. Secondary Outcome

Title	Rate of Engraftment
Description	Engraftment defined as the evidence of donor derived cells (more than 5%) by bone marrow chimerism studies in the presence of neutrophil recovery by day 28 post stem cell (SC) infusion. Engraftment date is the first day of three (3) consecutive days that the ANC exceeds 0.5 x109/L. Delayed engraftment is defined as the evidence of engraftment beyond day 28 post SC infusion achieved after the administration of therapeutic (high dose) hematopoietic growth factors.
Time Frame	From engraftment to 60 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Median (Full Range) [days]	18

5. Secondary Outcome

Title	2-year Progression-Free Survival
Description	Progression-free survival (PFS) is defined as the interval between day of transplant and day of death or disease progression.
Time Frame	First 25-35 days post transplant and then every 3 months for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	26 53.1%

6. Secondary Outcome

Title	2-year Overall Survival
Description	Overall Survival (OS) is defined as the interval between day of transplant and day of death.
Time Frame	First 25-35 days post transplant and then every 3 months for a maximum of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	33 67.3%

Adverse Events

Time Frame	Adverse events were collected from time of informed consent, first 25-35 days post transplant and then every 3 months up to 2 years.
Arm/Group Title	Busulfan + Fludarabine + Cyclophosphamide
Arm/Group Description	Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
All Cause Mortality
	Busulfan + Fludarabine + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Busulfan + Fludarabine + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	39/56 (69.6%)
Blood and lymphatic system disorders
Thrombocytopenia due to Valcyte	1/56 (1.8%)	1
Thrombocytopenia	1/56 (1.8%)	1
Cardiac disorders
Cardio-renal syndrome	1/56 (1.8%)	1
Eye disorders
Chronic ocular GvHD	1/56 (1.8%)	1
Gastrointestinal disorders
Chronic GI GvHD	1/56 (1.8%)	1
GI GvHD	3/56 (5.4%)	3
Neutropenic typhlitis	1/56 (1.8%)	1
General disorders
Death	39/56 (69.6%)	39
Hepatobiliary disorders
Liver GvHD	3/56 (5.4%)	3
Immune system disorders
Delayed engraftment due to Cytoxan	1/56 (1.8%)	1
Delayed Engraftment	1/56 (1.8%)	1
Graft Failure due to Relapsed MDS	1/56 (1.8%)	1
Graft Failure due to micro-environment	1/56 (1.8%)	1
Graft Failure due to Rejection	4/56 (7.1%)	4
Primary Graft Failure	1/56 (1.8%)	1
Infections and infestations
BK virus associated hemorrhagic cystitis	2/56 (3.6%)	2
Infections Viral	2/56 (3.6%)	2
Infections Bacterial	4/56 (7.1%)	5
Infections Fungal	3/56 (5.4%)	3
Presumed viral encephalitis	1/56 (1.8%)	1
Metabolism and nutrition disorders
Elevated bilirubin due to Sepsis	1/56 (1.8%)	1
Elevated alanine aminotransferase due to drug related	1/56 (1.8%)	1
Elevated bilirubin due to drug related	1/56 (1.8%)	1
Renal and urinary disorders
Renal insufficiency	1/56 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/56 (3.6%)	2
Presumed fungal pneumonia	1/56 (1.8%)	1
Skin and subcutaneous tissue disorders
Skin GVHD	1/56 (1.8%)	1
Vascular disorders
Hemorrhage due to low PLT	1/56 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Busulfan + Fludarabine + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	54/56 (96.4%)
Blood and lymphatic system disorders
Fluid overload	17/56 (30.4%)	17
Hemochromatosis	1/56 (1.8%)	1
Red cell dysplasia due to ABO incompatibility	1/56 (1.8%)	1
Thrombocytopenia due to drug related	2/56 (3.6%)	2
Cardiac disorders
Atrial fibrilation due to dexamethasone	1/56 (1.8%)	1
Atrial fibrilation	1/56 (1.8%)	1
Congestive heart failure	5/56 (8.9%)	5
Hypertension	2/56 (3.6%)	2
Hypertension due to Tacrolimus	1/56 (1.8%)	1
Hypotension due to Norvasc	1/56 (1.8%)	1
Hypotension	1/56 (1.8%)	1
Left ventricular dysfunction	1/56 (1.8%)	1
Tachycardia	1/56 (1.8%)	1
Eye disorders
Chronic ocular GvHD	4/56 (7.1%)	4
Ocular GvHD	1/56 (1.8%)	1
Propionibaterium acnes conjunctivitis	1/56 (1.8%)	1
Gastrointestinal disorders
Abdominal pain due to Doxycycline	1/56 (1.8%)	1
Abdominal pain	1/56 (1.8%)	1
Chronic upper GI GvHD	1/56 (1.8%)	1
Diarrhea	21/56 (37.5%)	22
Dysphagia due to radiation treatment	1/56 (1.8%)	1
Gastritis	1/56 (1.8%)	1
GI GvHD	9/56 (16.1%)	9
GI bleed of undetermnined cause	1/56 (1.8%)	1
Mucositis	48/56 (85.7%)	48
Nausea	48/56 (85.7%)	49
Nausea due to drug related	2/56 (3.6%)	2
Nausea due to CMV infection	1/56 (1.8%)	1
Oral GvHD	2/56 (3.6%)	2
Small bowel obstruction from pneumatosis coli	1/56 (1.8%)	1
Suspected Ganciclovir induced diarrhea	1/56 (1.8%)	1
Upper GI GvHD	9/56 (16.1%)	9
General disorders
Fevers	10/56 (17.9%)	10
Fevers due to ATG	19/56 (33.9%)	19
Fevers due to Engraftment Syndrome	1/56 (1.8%)	1
Fevers due to Transfusion	1/56 (1.8%)	2
Ulcer	1/56 (1.8%)	1
Hepatobiliary disorders
Liver GvHD	6/56 (10.7%)	9
Immune system disorders
Allergic reaction due to Platelet transfusion	1/56 (1.8%)	1
Allergic reaction due to Cell infusion	1/56 (1.8%)	1
Engraftment syndrome	1/56 (1.8%)	1
Suspected cGvHD	1/56 (1.8%)	1
Suspected engraftment syndrome	1/56 (1.8%)	1
Infections and infestations
BK virus associated hemorrhagic cystitis	24/56 (42.9%)	24
Demodex folliculitis	1/56 (1.8%)	1
Folliculitis	3/56 (5.4%)	3
Infections Bacterial	36/56 (64.3%)	65
Infections Fungal	5/56 (8.9%)	6
Infections Viral	33/56 (58.9%)	51
Neutropenic fevers	30/56 (53.6%)	30
Metabolism and nutrition disorders
Elevated alanine aminotransferase	6/56 (10.7%)	6
Elevated alanine aminotransferase due to drug related	7/56 (12.5%)	7
Elevated alkaline phosphatase	4/56 (7.1%)	4
Elevated alkaline phosphatase due to drug related	4/56 (7.1%)	4
Elevated bilirubin	9/56 (16.1%)	9
Elevated bilirubin due to RBC transfusions	1/56 (1.8%)	1
Elevated bilirubin due to drug related	4/56 (7.1%)	4
Elevated lactate dehydrogenase due to Vancomycin	1/56 (1.8%)	1
Magnesium induced diarrhea	1/56 (1.8%)	1
Steroid induced hyperglycemia	16/56 (28.6%)	16
Suspected metabolic encephalopathy	1/56 (1.8%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/56 (1.8%)	1
Bone pain due to Neupogen	1/56 (1.8%)	1
Myopathy	2/56 (3.6%)	2
Myopathy due to Tramadol	1/56 (1.8%)	1
Steroid-Induced Myopathy	3/56 (5.4%)	3
Nervous system disorders
Altered mental status changes due to drug related	6/56 (10.7%)	6
Altered mental status changes due to ATG	1/56 (1.8%)	1
Altered mental status changes	3/56 (5.4%)	3
Dizziness due to Dilantin	1/56 (1.8%)	1
Headaches	3/56 (5.4%)	3
Neuropathy	1/56 (1.8%)	1
Suspected migraine	1/56 (1.8%)	1
Renal and urinary disorders
Renal insufficiency	1/56 (1.8%)	1
Renal insufficiency due to Nephrotoxins	3/56 (5.4%)	3
Renal insufficiency due to Pyelonephritis	1/56 (1.8%)	1
Renal insufficiency due to Overt diuresis	1/56 (1.8%)	1
Renal insufficiency due to drug related	9/56 (16.1%)	9
Renal insufficiency due to Obstructive neuropathy	1/56 (1.8%)	1
Renal insufficiency due to Obstructive uropathy	1/56 (1.8%)	1
Renal insufficiency due to Hemorrhagic cystitis	1/56 (1.8%)	1
Reproductive system and breast disorders
Severe vulvar discomfort	1/56 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	7/56 (12.5%)	7
Shortness of breath due to platelet transfusion	1/56 (1.8%)	1
Skin and subcutaneous tissue disorders
Cellulitis	2/56 (3.6%)	2
Chronic skin GvHD	1/56 (1.8%)	1
Dermatitis drug eruption vs GvHD	1/56 (1.8%)	1
Pruritus due to Bactrim	1/56 (1.8%)	1
Rash	5/56 (8.9%)	5
Rash due to ATG	3/56 (5.4%)	3
Rash due to drug related	5/56 (8.9%)	6
Skin GVHD	25/56 (44.6%)	27
Vascular disorders
Deep vein thrombosis	1/56 (1.8%)	1
Hemorrhage of undetermined etiology	1/56 (1.8%)	1
Line related deep vein thrombosis	4/56 (7.1%)	4

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.