SCURT: Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601)

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT00745420
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH), National Marrow Donor Program (Other), Sickle Cell Disease Clinical Research Network (Other)
• Enrollment: 30
• Locations: 19
• Arm: 1
• Duration (Months): 97
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Prior to undergoing a transplant, people typically receive a conditioning regimen of high doses of chemotherapy and other medications to prepare the body to accept the transplant. A conditioning regimen that uses lower doses of chemotherapy and medications may be safer for transplant recipients. This study will evaluate the safety and effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in children with severe SCD who receive a reduced intensity conditioning regimen prior to the transplant.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Biological: Hematopoietic Stem Cell Transplantation	Phase 2

Detailed Description

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, also called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen to vital organs, such as the brain, heart, lungs, and kidneys. Defective hemoglobin damages red blood cells. The damaged cells, in turn, can block blood flow in vessels and block oxygen and nutrients from reaching organs. For people with severe forms of SCD, one treatment option is a bone marrow transplant, which may correct the abnormal blood cell production problem. In most cases, bone marrow transplants are performed in people who have a healthy sibling with the same tissue type. If people do not have a sibling with the same tissue type, it is possible for them to receive a blood stem cell transplant from an unrelated donor through bone marrow transplant .

Traditionally, people with SCD who are undergoing a bone marrow transplant receive high doses of chemotherapy and medications before the transplant as part of the conditioning regimen to prepare their immune system to accept the donor cells. Participants will experience fewer side effects with a reduced intensity conditioning regimen than with a more intense conditioning regimen. The purpose of this study is to determine the safety and effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in children with severe SCD who receive a reduced intensity conditioning regimen before the transplant. Specifically, researchers will evaluate whether the reduced intensity conditioning regimen is successful in allowing donor cells to settle and grow successfully, in preventing the production of SCD-damaged red blood cells, and in limiting SCD-related organ damage.

This study will enroll children with severe SCD who lack a sibling with the same tissue type who can serve as their donor. Participants will attend a study visit prior to the transplant to undergo a blood collection, neurocognitive testing to measure learning and brain function, and magnetic resonance angiogram (MRA) and magnetic resonance imaging (MRI) scans. Questionnaires to assess quality of life will also be completed. Twenty-two days before the transplant, participants will begin receiving a reduced intensity conditioning regimen of chemotherapy and medications to prepare them for the transplant. Eight days before the transplant, participants will be admitted to the hospital and will continue the conditioning regimen. Participants will then receive the bone marrow transplant. After the transplant, participants will receive immunosuppression medications for at least 6 months to prevent graft-versus-host disease (GVHD), which may occur if the immune cells from the donated bone marrow attacks the body of the recipient. One week after the transplant, participants will receive granulocyte-colony-stimulating factor (G-CSF), which is a natural protein that increases the white blood cell count and helps protect the body against infections. Participants will receive G-CSF until their white blood cell level is normal again. Participants will remain in the hospital and be closely monitored for signs of infection or other complications until study researchers feel it is safe for them to return home.

After leaving the hospital, participants will attend study visits weekly during Weeks 1 to 8, at Day 60, weekly during Weeks 9 to 14, at Day 100, at Month 6, and at Years 1 and 2. At all study visits, a blood collection, medical history review, and physical exam will occur. In addition, at Day 100, Month 6, and Years 1 and 2, questionnaires to assess quality of life will be completed. At select visits the following procedures will also occur: lung function testing, heart function testing, MRA and MRI scans, and neurocognitive testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children With Severe Sickle Cell Disease (BMT CTN #0601)
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Hematopoietic Stem Cell Transplantation Bone Marrow Transplant with GVHD Prophylaxis Regimen

Biological: Hematopoietic Stem Cell Transplantation; The stem cell transplant preparative regimen is listed below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant. Alemtuzumab: Children weighing 10 kg or more will receive 10 mg, 15 mg, and 20 mg intravenously (IV) on Days -21, -20, and -19, respectively Fludarabine: 30 mg/m^2/day IV on Days -8 through -4 Melphalan: 140 mg/m^2 IV on Day -3 Rest on Days -2 and -1 Transplant occurs on Day 0 GVHD prophylaxis: Tacrolimus or cyclosporine beginning Day -3, methotrexate (7.5 mg/m2/day) Day 1, 3 and 6 and methylprednisolone/prednisone on Day +7 to +28 followed by a taper if there is no GVHD; Other Names: Bone Marrow Transplant

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Event-Free Survival (EFS) [2 years]

   EFS is defined as percentage of participants that have not had an event. Primary or secondary graft rejection, disease recurrence, or death will count as events for this endpoint.

Secondary Outcome Measures

1. Percentage of Participants With Overall Survival (OS) [2 years]

   OS is defined as the percentage of participants that have not died.

2. Neutrophil and Platelet Recovery [Up to 100 days]

   Time to neutrophil recovery is defined as the time of the first of three measurements on consecutive days where the patient has an absolute neutrophil count of >= 500/uL following conditioning regimen induced nadir. Time to platelet recovery is defined as the time of the first of three measurements on consecutive days where the patient has achieved a platelet count > 50,000/uL and is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.

3. Graft Rejection [1 year]

   Primary graft rejection is defined as the presence of less than 20% donor cells as assessed by peripheral blood or bone marrow chimerism assays on or after Day 42. Secondary graft rejection is defined as the presence of less than 20% donor derived hematopoietic cells in peripheral blood or bone marrow that occurs after prior evidence of 20% or greater donor cells.

4. Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD) [100 days]

   Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

5. Percentage of Participants With Chronic GVHD [1 year post-transplant]

   Chronic GVHD is defined per NIH 2005 Consensus Criteria.

6. Number of Participants With Chronic GVHD by Severity [1 year post-transplant]

   Chronic GVHD severity is defined per NIH 2005 Consensus Criteria.

7. Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES) [1 year]

8. Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL) [100 days post-transplant]

   HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

9. Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL) [100 days post-transplant]

   HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

10. Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL) [180 days post-transplant]

    HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

11. Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL) [180 days post-transplant]

    HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

12. Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL) [1 year post-transplant]

    HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

13. Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL) [1 year post-transplant]

    HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• SCD (genotype hemoglobin SS disease [Hb SS], genotype hemoglobin SC disease [HbSC],sickle ß°[Sß°] thalassemia, or sickle ß^+[Sß^+]thalassemia) with one or more of the following:

1. Patients must have symptomatic SCD (genotype Hb SS, Hb SC, Sß° thalassemia or Sß+ thalassemia), AND have 1 or more of the following clinical complications:(i) Clinically significant neurologic event (stroke) or any neurologic deficit lasting more than 24 hours that is accompanied by an infarct on cerebral MRI; OR (ii) patients who have a Transcranial Doppler (TCD) velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement greater than 185 cm/sec by the imaging technique) measured at a minimum of 2 separate occasions one month or more apart; OR,

2. Minimum of two episodes of acute chest syndrome in the 2 years before study entry, defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea, wheezing, rales, or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures

3. History of 3 or more severe pain events per year in the 2 years before study entry

• Lansky/Karnofsky performance score greater than or equal to 40

• Patients must have an unrelated adult bone marrow donor who is Human Leukocyte Antigen (HLA)-matched at 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.

• Patients with adequate physical function: a)Cardiac: Left ventricular ejection fraction (LVEF) greater than 40%, or LV shortening fraction greater than 26%; b) Pulmonary: Pulse oxymetry with a baseline O2 saturation of greater than or equal to 85% is required for all patients, Carbon Monoxide Diffusing Capacity (DLCO) greater than 40% (corrected for hemoglobin) for patients in whom pulmonary function testing can be performed; c) Renal: Serum creatinine less than or equal to 1.5 x upper limit of normal for age and glomerular filtration rate (GFR) greater than 100 mL/min/1.73 m. For patients older than or equal to 16 years of age, GFR should be greater than 70 mL/min/1.73 m^2; d) Hepatic: Serum conjugated (direct) bilirubin less than 2x upper limit of normal for age as per local laboratory; alanine transaminase (ALT) and aspartate transaminase (AST) less than 5 times upper limit of normal as per local laboratory.

• If the patient has been receiving chronic transfusion therapy for more than or equal to 1 year AND has clinical evidence of iron overload (serum ferritin level of greater than 1000 ng/ml), a liver biopsy shall be obtained within 90 days of starting conditioning therapy (alemtuzumab). Histologic exam of the liver must document absence of bridging fibrosis or cirrhosis of the liver. In other cases, a liver biopsy is optional.

• Hemoglobin S (Hb S) level less than or equal to 45%, seven days prior to initiation of alemtuzumab

Exclusion Criteria:

• Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen

• Pregnant or breastfeeding

• Patients with 8/8 HLA-matched family donors able to donate

• Seropositivity for HIV

• Prior allogeneic marrow or stem cell transplant

• Iron chelation must be discontinued more than or equal to 48 hours before initiating the conditioning regimen

• Hydroxyurea (if receiving this therapy) must be discontinued more than or equal to 48 hours before initiating the conditioning regimen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	University of Miami	Miami	Florida	United States	33136
4	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
5	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60614
6	Children's Hospital of New Orleans/LSUMC CCOP	New Orleans	Louisiana	United States	70118
7	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48105
8	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
9	Children's Mercy Hospital and Clinics	Kansas City	Missouri	United States	64108
10	Washington University, St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
11	Cohen Children's Hospital	New Hyde Park	New York	United States	11040
12	Columbia University Medical Center	New York	New York	United States	10032
13	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina	United States	27599
14	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
15	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	Baylor College of Medicine/The Methodist Hospital	Houston	Texas	United States	77030
18	Virginia Commonwealth University	Richmond	Virginia	United States	23298
19	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53211

Sponsors and Collaborators

• Medical College of Wisconsin
• National Heart, Lung, and Blood Institute (NHLBI)
• Blood and Marrow Transplant Clinical Trials Network
• National Cancer Institute (NCI)
• National Marrow Donor Program
• Sickle Cell Disease Clinical Research Network

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for the Blood and Marrow Transplant Clinical Trials Network Web site
• Click here for the National Marrow Donor Program Web site

Publications

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. 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 Dec;11(12):945-56.
• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. Review.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT00745420
• Other Study ID Numbers: BMTCTN0601; U01HL069294; 5U24CA076518
• First Posted: Sep 3, 2008
• Last Update Posted: May 11, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Medical College of Wisconsin: Sickle Cell Disease; Sickle Cell Anemia
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between August 2008 and April 2014 from 19 different transplant centers.

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Overall Participants	29
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	14
Sex: Female, Male (Count of Participants)
Female	13 44.8%
Male	16 55.2%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	26 89.7%
Hispanic or Latino	3 10.3%
Indications for Transplant (Count of Participants)
Stroke	12 41.4%
Trans cranial doppler velocity > 200cm/s	2 6.9%
Acute chest syndrome	4 13.8%
Vaso-occlusive pain crisis	12 41.4%
Chronic Blood Transfusion Prior to Transplant (Count of Participants)
Count of Participants [Participants]	14 48.3%
Karnofsky Performance Score (Count of Participants)
100	17 58.6%
90	9 31%
80	2 6.9%
70	1 3.4%
Cytomegalovirus (CMV) Status (Count of Participants)
CMV - donor and recipient	8 27.6%
CMV + donor and recipient	9 31%
CMV - donor and CMV + recipient	3 10.3%
CMV + donor and CMV - recipient	9 31%
Donor Blood Type Match (Count of Participants)
ABO Blood group matched	15 51.7%
ABO Blood group major mismatch	9 31%
ABO Blood group minor mismatch	5 17.2%
Donor Gender Match (Count of Participants)
Gender matched transplants	15 51.7%
Female donor, male recipient	7 24.1%
Male donor, female recipient	7 24.1%
Donor Age (years) [Median (Full Range) ]
Median (Full Range) [years]	35
Donor Race/Ethnicity (Count of Participants)
Caucasian	11 37.9%
Black or African American	11 37.9%
Multiracial	5 17.2%
Not Reported	2 6.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Event-Free Survival (EFS)
Description	EFS is defined as percentage of participants that have not had an event. Primary or secondary graft rejection, disease recurrence, or death will count as events for this endpoint.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
1 year	76 262.1%
2 years	69 237.9%

2. Secondary Outcome

Title	Percentage of Participants With Overall Survival (OS)
Description	OS is defined as the percentage of participants that have not died.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
1 year	86 296.6%
2 years	79 272.4%

3. Secondary Outcome

Title	Neutrophil and Platelet Recovery
Description	Time to neutrophil recovery is defined as the time of the first of three measurements on consecutive days where the patient has an absolute neutrophil count of >= 500/uL following conditioning regimen induced nadir. Time to platelet recovery is defined as the time of the first of three measurements on consecutive days where the patient has achieved a platelet count > 50,000/uL and is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.
Time Frame	Up to 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
Neutrophil Recovery	12
Platelet Recovery	24

4. Secondary Outcome

Title	Graft Rejection
Description	Primary graft rejection is defined as the presence of less than 20% donor cells as assessed by peripheral blood or bone marrow chimerism assays on or after Day 42. Secondary graft rejection is defined as the presence of less than 20% donor derived hematopoietic cells in peripheral blood or bone marrow that occurs after prior evidence of 20% or greater donor cells.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
Primary Graft Rejection	2 6.9%
Secondary Graft Rejection	1 3.4%

5. Secondary Outcome

Title	Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)
Description	Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
Grade II-IV Acute GVHD	28 96.6%
Grade III-IV Acute GVHD	17 58.6%

6. Secondary Outcome

Title	Percentage of Participants With Chronic GVHD
Description	Chronic GVHD is defined per NIH 2005 Consensus Criteria.
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
Number (95% Confidence Interval) [percentage of participants]	62 213.8%

7. Secondary Outcome

Title	Number of Participants With Chronic GVHD by Severity
Description	Chronic GVHD severity is defined per NIH 2005 Consensus Criteria.
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
None	10 34.5%
Mild	6 20.7%
Moderate	8 27.6%
Severe	5 17.2%

8. Secondary Outcome

Title	Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	29
Number (95% Confidence Interval) [percentage of participants]	34 117.2%

9. Secondary Outcome

Title	Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

Participants age 10 years or older that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	18
Self esteem score	-0.59 (4.51)
General health perception score	-1.90 (4.29)
Change in health score	0.33 (0.45)

10. Secondary Outcome

Title	Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

Parent proxies of participants that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	21
Self esteem scale score	-15.12 (4.89)
General health perception score	11.13 (2.51)
Change in health score	0.90 (0.38)

11. Secondary Outcome

Title	Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	180 days post-transplant

Outcome Measure Data

Analysis Population Description

Participants age 10 years or older that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	16
Self esteem scale score	-4.33 (5.87)
General health perception score	-6.69 (4.99)
Change in health score	0.19 (0.52)

12. Secondary Outcome

Title	Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	180 days post-transplant

Outcome Measure Data

Analysis Population Description

Parent proxies of participants that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	20
Self esteem scale score	-11.46 (6.28)
General health perception score	7.63 (3.31)
Change in health score	1.15 (0.36)

13. Secondary Outcome

Title	Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

Participants age 10 years or older that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	13
Self esteem scale score	4.97 (5.33)
General health perception score	6.99 (6.35)
Change in health score	1.46 (0.35)

14. Secondary Outcome

Title	Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Description	HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87). The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated. Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being. Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
Time Frame	1 year post-transplant

Outcome Measure Data

Analysis Population Description

Parent proxies of participants that returned the HRQL surveys

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
Measure Participants	15
Self esteem scale score	-3.61 (6.66)
General health perception score	8.89 (5.27)
Change in health score	1.53 (0.48)

Adverse Events

Time Frame	2 years post-transplant
Adverse Event Reporting Description	Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	Bone Marrow Transplant with GVHD Prophylaxis Regimen
All Cause Mortality
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	21/29 (72.4%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/29 (3.4%)	1
Cardiac disorders
Cardiac arrest	1/29 (3.4%)	1
Gastrointestinal disorders
Pancreatitis	1/29 (3.4%)	1
General disorders
Death	1/29 (3.4%)	1
Infections and infestations
Sepsis	1/29 (3.4%)	1
Septic shock	1/29 (3.4%)	1
Staphylococcal sepsis	1/29 (3.4%)	1
Investigations
Oxygen saturation decreased	1/29 (3.4%)	1
Nervous system disorders
Cerebrovascular accident	1/29 (3.4%)	1
Depressed level of consciousness	1/29 (3.4%)	1
Posterior reversible encephalopathy syndrome	2/29 (6.9%)	2
Seizure	1/29 (3.4%)	1
Somnolence	1/29 (3.4%)	1
Psychiatric disorders
Mental status changes	1/29 (3.4%)	1
Renal and urinary disorders
Acute kidney injury	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/29 (3.4%)	1
Respiratory failure	2/29 (6.9%)	2
Skin and subcutaneous tissue disorders
Rash macular	1/29 (3.4%)	1
Surgical and medical procedures
Cholecystectomy	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	2/29 (6.9%)
Nervous system disorders
Seizure	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/29 (3.4%)	1

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.