Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Sickle Cell Anemia
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.
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.
Interventions
BIOLOGICALHematopoietic 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
Sponsors
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Sickle Cell Disease Clinical Research Network
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 19 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. 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 |
| Percentage of Participants With Chronic GVHD | 1 year post-transplant | Chronic GVHD is defined per NIH 2005 Consensus Criteria. |
| Number of Participants With Chronic GVHD by Severity | 1 year post-transplant | Chronic GVHD severity is defined per NIH 2005 Consensus Criteria. |
| Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES) | 1 year | — |
| Percentage of Participants With Overall Survival (OS) | 2 years | OS is defined as the percentage of participants that have not died. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled between August 2008 and April 2014 from 19 different transplant centers.
Participants by arm
| Arm | Count |
|---|---|
| Hematopoietic Stem Cell Transplantation Bone Marrow Transplant with GVHD Prophylaxis Regimen | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 1 |
Baseline characteristics
| Characteristic | Hematopoietic Stem Cell Transplantation |
|---|---|
| Age, Continuous | 14 years |
| Chronic Blood Transfusion Prior to Transplant | 14 Participants |
| Cytomegalovirus (CMV) Status CMV - donor and CMV + recipient | 3 Participants |
| Cytomegalovirus (CMV) Status CMV + donor and CMV - recipient | 9 Participants |
| Cytomegalovirus (CMV) Status CMV - donor and recipient | 8 Participants |
| Cytomegalovirus (CMV) Status CMV + donor and recipient | 9 Participants |
| Donor Age | 35 years |
| Donor Blood Type Match ABO Blood group major mismatch | 9 Participants |
| Donor Blood Type Match ABO Blood group matched | 15 Participants |
| Donor Blood Type Match ABO Blood group minor mismatch | 5 Participants |
| Donor Gender Match Female donor, male recipient | 7 Participants |
| Donor Gender Match Gender matched transplants | 15 Participants |
| Donor Gender Match Male donor, female recipient | 7 Participants |
| Donor Race/Ethnicity Black or African American | 11 Participants |
| Donor Race/Ethnicity Caucasian | 11 Participants |
| Donor Race/Ethnicity Multiracial | 5 Participants |
| Donor Race/Ethnicity Not Reported | 2 Participants |
| Indications for Transplant Acute chest syndrome | 4 Participants |
| Indications for Transplant Stroke | 12 Participants |
| Indications for Transplant Trans cranial doppler velocity > 200cm/s | 2 Participants |
| Indications for Transplant Vaso-occlusive pain crisis | 12 Participants |
| Karnofsky Performance Score 100 | 17 Participants |
| Karnofsky Performance Score 70 | 1 Participants |
| Karnofsky Performance Score 80 | 2 Participants |
| Karnofsky Performance Score 90 | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 29 |
| serious Total, serious adverse events | 21 / 29 |
Outcome results
Primary
Percentage of Participants With Event-Free Survival (EFS)
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Event-Free Survival (EFS) | 1 year | 76 percentage of participants |
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Event-Free Survival (EFS) | 2 years | 69 percentage of participants |
Secondary
Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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
Population: Parent proxies of participants that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Self esteem scale score | -3.61 units on a scale | Standard Error 6.66 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL) | General health perception score | 8.89 units on a scale | Standard Error 5.27 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Change in health score | 1.53 units on a scale | Standard Error 0.48 |
Secondary
Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL)
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
Population: Participants age 10 years or older that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL) | Self esteem scale score | 4.97 units on a scale | Standard Error 5.33 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL) | General health perception score | 6.99 units on a scale | Standard Error 6.35 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL) | Change in health score | 1.46 units on a scale | Standard Error 0.35 |
Secondary
Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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
Population: Parent proxies of participants that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Self esteem scale score | -15.12 units on a scale | Standard Error 4.89 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | General health perception score | 11.13 units on a scale | Standard Error 2.51 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Change in health score | 0.90 units on a scale | Standard Error 0.38 |
Secondary
Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL)
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
Population: Participants age 10 years or older that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL) | Self esteem score | -0.59 units on a scale | Standard Error 4.51 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL) | General health perception score | -1.90 units on a scale | Standard Error 4.29 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL) | Change in health score | 0.33 units on a scale | Standard Error 0.45 |
Secondary
Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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
Population: Parent proxies of participants that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Self esteem scale score | -11.46 units on a scale | Standard Error 6.28 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | General health perception score | 7.63 units on a scale | Standard Error 3.31 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL) | Change in health score | 1.15 units on a scale | Standard Error 0.36 |
Secondary
Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL)
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
Population: Participants age 10 years or older that returned the HRQL surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL) | Self esteem scale score | -4.33 units on a scale | Standard Error 5.87 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL) | General health perception score | -6.69 units on a scale | Standard Error 4.99 |
| Hematopoietic Stem Cell Transplantation | Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL) | Change in health score | 0.19 units on a scale | Standard Error 0.52 |
Secondary
Graft Rejection
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Graft Rejection | Primary Graft Rejection | 2 Participants |
| Hematopoietic Stem Cell Transplantation | Graft Rejection | Secondary Graft Rejection | 1 Participants |
Secondary
Neutrophil and Platelet Recovery
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Neutrophil and Platelet Recovery | Neutrophil Recovery | 12 days |
| Hematopoietic Stem Cell Transplantation | Neutrophil and Platelet Recovery | Platelet Recovery | 24 days |
Secondary
Number of Participants With Chronic GVHD by Severity
Chronic GVHD severity is defined per NIH 2005 Consensus Criteria.
Time frame: 1 year post-transplant
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Number of Participants With Chronic GVHD by Severity | None | 10 Participants |
| Hematopoietic Stem Cell Transplantation | Number of Participants With Chronic GVHD by Severity | Mild | 6 Participants |
| Hematopoietic Stem Cell Transplantation | Number of Participants With Chronic GVHD by Severity | Moderate | 8 Participants |
| Hematopoietic Stem Cell Transplantation | Number of Participants With Chronic GVHD by Severity | Severe | 5 Participants |
Secondary
Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)
Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD) | Grade II-IV Acute GVHD | 28 percentage of participants |
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD) | Grade III-IV Acute GVHD | 17 percentage of participants |
Secondary
Percentage of Participants With Chronic GVHD
Chronic GVHD is defined per NIH 2005 Consensus Criteria.
Time frame: 1 year post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Chronic GVHD | 62 percentage of participants |
Secondary
Percentage of Participants With Overall Survival (OS)
OS is defined as the percentage of participants that have not died.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Overall Survival (OS) | 1 year | 86 percentage of participants |
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Overall Survival (OS) | 2 years | 79 percentage of participants |
Secondary
Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES)
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES) | 34 percentage of participants |