Severe Aplastic Anemia
Conditions
Keywords
Haploidentical Bone Marrow, Hematopoietic Stem Cell Transplant (HSCT), Severe Aplastic Anemia (SAA), Antithymocyte Globulin (ATG)
Brief summary
This study is a prospective, multicenter phase II study with patients receiving haploidentical transplantation for Severe Aplastic Anemia (SAA). The primary objective is to assess overall survival (OS) at 1 year post-hematopoietic stem cell transplantation (HSCT).
Detailed description
Acquired SAA is a rare bone marrow failure disorder with an estimated annual incidence of 2 cases per million and with over 600 new cases in the United States each year. A major challenge in treating acquired SAA is the management of patients who are refractory to immunosuppressant therapy (IST) or have relapsed after IST. HSCT is the only curative option for these patients but many are ineligible because they lack a suitable donor. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) seeks to increase options for these patients by using novel therapeutic strategies of GVHD prophylaxis with PTCy to expand the donor pool to include haploidentical donors. The goal of this protocol is to test whether optimized approaches using haploidentical donors will achieve acceptable outcomes in SAA patients.
Interventions
Administration of ATG will be 0.5 mg/kg IV on Day -9 over 6 hours and 2 mg/kg IV on Days -8 and -7 over 4 hours.
DRUGFludarabine
Fludarabine dose will be 30 mg/m\^2 IV daily for 5 days from Day -6 to Day -2.
DRUGCyclophosphamide
Cyclophosphamide dose will be 14.5 mg/kg IV daily for 2 days (Day -6 to Day -5) prior to transplantation and 50 mg/kg IV daily for 2 days (Day +3 to Day +4) after transplantation.
RADIATIONTotal Body Irradiation (TBI)
TBI is to be delivered in a single dose of 200 cGy on Day -1.
PROCEDUREHaplo HSCT
Eligible patients without a fully matched related or unrelated donor available will undergo haploidentical bone marrow transplant.
DRUGTacrolimus
Tacrolimus should be started on Day +5 and administered to maintain a level of 10-15 ng/mL.
DRUGMycophenolate mofetil (MMF)
MMF dose will be 15 mg/kg PO three times a day (TID) up to 1 gm TID (or IV equivalent) starting on Day +5.
DRUGG-CSF
G-CSF will be given IV or SQ starting on Day +5 at 5 mcg/kg/day until ANC is \> 1500 for 3 days.
Sponsors
Medical College of Wisconsin
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patient is \< 75 years of age at time of enrollment. 2. Confirmed diagnosis of SAA, either from initial diagnosis or follow-up assessments, defined as: 1. Bone marrow cellularity \< 25% or marrow cellularity \< 50% but with \< 30% residual hematopoietic cells. 2. Two out of three of the following (in peripheral blood): Neutrophils \< 0.5 x10\^9/L, Platelets \< 20 x10\^9/L, or Reticulocyte count \< 20 x10\^9/L (\<60 x 10\^9/L using an automated analysis) 3. No suitable fully matched related sibling donor (6/6 match for human leukocyte antigen (HLA)-A and B at intermediate or high resolution and DRB1 at high resolution using DNA-based typing) available. 4. Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA. 5. Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc. Eligible haploidentical donors will have 2-4 mismatches if HLA-A, -B, -C, and -DRB1 typing is used; 2-5 mismatches if HLA-A, -B, -C, -DRB1, and -DQB1 typing is used; and 2-6 mismatches if HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 typing is used. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must demonstrate that they are a full haplotype match by being identical at a minimum of one allele (at high resolution DNA-based typing) at the following genetic loci: HLA-A, -B, -C, and DRB1 if 8 allele typing is used; HLA-A, -B, -C, -DRB1, and -DQB1 if 10 allele typing is used; and HLA-A, -B, -C, -DRB1-, DQB1, and -DPB1 is 12 allele typing is used by the local center. See Section 2.4 for additional information. 6. Patient and/or legal guardian must sign informed consent for HSCT. 7. The haplo donor and/or legal guardian must be able to sign informed consent documents. 8. The potential haplo donor must be willing and able to donate bone marrow. 9. The weight of the haplo donor must be ≥ 20 kg. 10. Adequate organ function defined as: 1. Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40%. For patients aged \< 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or Multi Gated Acquisition Scan (MUGA) may be substituted for LVEF. 2. Hepatic: Total bilirubin \< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5.0 x ULN for age. 3. Renal: For patients \> 13.0 years of age at the time of enrollment: estimated creatinine clearance \> 50 mL/minute (using the Cockcroft-Gault formula and actual body weight). For patients \< 13.0 years of age at enrollment: Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m\^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m\^2. 4. Pulmonary: For patients \> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) \> 40% and forced expiratory volume in one second (FEV1) \> 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) \> 50% predicted. For patients \< 13.0 years of age unable to perform pulmonary function tests (PFT) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care (e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%)). 11. Karnofsky or Lansky performance status ≥ 60%. 12. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.
Exclusion criteria
1. Inherited bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center standard. 2. Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7). 3. Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) \> 1000 by solid phase immunoassay). 4. Prior allogeneic stem cell transplant. 5. Prior solid organ transplant. 6. Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® that would prohibit use for the patient as this study requires use of the Thymoglobulin® preparation of ATG. 7. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment. 8. Seropositive for the human immunodeficiency virus (HIV). 9. Active Hepatitis B or C determined by a detectable viral load of HBV or HCV. 10. Female patients who are pregnant (per institutional practice) or breast-feeding. 11. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent \> 5 years previously will be allowed. Cancer treated with curative intent ≤ 5 years previously will not be allowed unless approved by the Protocol Chairs and/or Protocol Officer. 12. Alemtuzumab or ATG within 2 weeks of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Survival (OS) | 1 year | Overall survival (OS) is the primary endpoint of this study. The time to this event is the time from transplant to death from any cause or last follow-up or 1 year from transplant, whichever occurs first. The one-year OS probability and its 95% confidence interval were estimated using the Kaplan-Meier estimator and Greenwood's formula. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Neutrophil Recovery | Day 28 and 56 | Neutrophil recovery is achieving an absolute neutrophil count (ANC) \> 0.5 x10\^9/L for three consecutive measurements on different days, with the first of the three days being defined as the day of neutrophil engraftment. The cumulative percentage of neutrophil engraftment was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to neutrophil engraftment treated as a competing risk. |
| Percentage of Participants With Platelet Recovery | Day 100 | Platelet recovery is defined by achieving a platelet count \> 20 x 10\^9/L with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be defined as the day of platelet engraftment. The cumulative percentage of platelet engraftment was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to platelet engraftment treated as a competing risk. |
| Participants Alive With Sustained Engraftment | 1 year | Being alive and engrafted is defined as not having experienced death, primary graft failure, or secondary graft failure. Donor cell engraftment is defined as donor chimerism greater than or equal to 5% on or after Day 56 after transplantation. Chimerism may be evaluated in whole blood or blood cell fractions, including CD3 and CD33 or CD15 fractions. For this protocol, lineage-specific, myeloid, and T cell chimerisms are required. This endpoint was adjudicated by the Endpoint Review Committee (ERC) and ERC data was used for the analysis. |
| Percentage of Participants With Graft-Failure-Free Survival | 1 year | Events for Graft-Failure-Free Survival (GFFS) including death, primary graft failure, secondary graft failure. The time to this event is the time from transplant to death from any cause, or graft failure, or last follow-up, or 1 year from transplant, whichever occurs first. For patients experiencing primary graft failure, Day 0.1 was used for primary graft failure event date to count the event in. The one-year GFFS probability and its 95% confidence interval were estimated using the Kaplan-Meier estimator and Greenwood's formula. |
| Percentage of Participants With Primary Graft Failure | Day 56 | Primary graft failure is defined by the lack of neutrophil engraftment by Day 56 post-HSCT or failure to achieve at least 5% donor chimerism (whole blood or marrow) on any measurements up to and including Day +56. For this protocol, lineage-specific, myeloid, and T cell chimerisms are required. Myeloid engraftment might not proceed at the same rate as T cell engraftment. If myeloid has greater than or equal to 5% donor, even if T cell compartment does not, this is not considered primary graft failure. Secondary graft failure is defined by initial neutrophil engraftment (ANC greater than or equal to 0.5 x 10\^8/L measured for 3 consecutive measurements on different days) followed by sustained subsequent decline in ANC to less than 0.5 x 10\^9/L for three consecutive measurements on different days or initial whole blood or marrow donor chimerism greater than or equal to 5%, but then declining to less than 5% on subsequent measurements or second infusion/transplant given for graft failure. |
| Percentage of Participants With Secondary Graft Failure | 1 year | Secondary graft failure is defined as any one of the following: 1. Initial neutrophil engraftment (ANC greater than or equal to 0.5 x10\^9/L measured for three consecutive measurements on different days) followed by sustained subsequent decline in ANC to less than 0.5 x 10\^9/L for three consecutive measurements on different days; 2. Initial whole blood or marrow donor chimerism greater than or equal to 5%, but then declining to less than 5% on subsequent measurements; 3. Second infusion/transplant given after Day 56 for graft failure. |
| Participants Alive With Autologous Recovery | 1 year | Autologous recovery is defined as ANC \> 0.5 x 10\^9/L and transfusion independence but with \< 5% donor chimerism (whole blood or m. arrow). This endpoint was reviewed and adjudicated by ERC. The analysis is based on ERC data. |
| Percentage of Participants With Acute Graft-vs-host-disease (GVHD) | Day 100 | Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The time of onset of grades II-IV and grades III-IV acute GVHD were recorded. This endpoint is evaluated through 100 days post-transplant. Cumulative percentage of acute GVHD post-transplant are estimated using the cumulative incidence function, treating death prior to acute GVHD as the competing risk. |
| Participants With Maximum Acute GVHD | Day 100 | Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). Acute GVHD grading is performed by the consensus conference criteria (Przepiorka et al. 1995) with higher grade indicating worse outcomes. Grade I acute GVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-4 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver. Maximum grade of acute GVHD through 100 days post transplant is reported. |
| Percentage of Participants With Chronic GVHD | 1 year | The event for this secondary endpoint is any chronic GVHD based on 2014 NIH Consensus Criteria. This includes mild, moderate and severe chronic GVHD. The analyses of Chronic GVHD use the site-reported data. The cumulative percentage of chronic GVHD is computed using the cumulative incidence function, treating death prior to chronic GVHD as a competing risk. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD will also be recorded. This secondary endpoint of chronic GVHD will include mild, moderate and severe chronic GVHD based on NIH Consensus Criteria. |
| Number of Participants Experiencing Chronic GVHD With Maximum Severity | 1 year | The event for this secondary endpoint is any chronic GVHD based on 2014 NIH Consensus Criteria. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD will also be recorded. The overall chronic GVHD severity is based on the eight organs score. The maximin severity level of chronic GVHD include mild, moderate and severe. |
| Immune Reconstitution of Flow Cytometry | Baseline, Days 100, 180, and 365 | Quantitative assessments of peripheral blood CD3, CD4, CD8, CD19, and CD56 positive lymphocytes will be done through flow cytometric analysis. |
| Immune Reconstitution of Quantitative Immunoglobulins | baseline and 1-year | Quantitative immunoglobulins of IgA, IgG, IgM were done at baseline and 1-year post-transplant. |
| Participants With Infections of Maximum Grade 2 and Grade 3 | 1 Year | Number of participants who reported the Maximum Infection Severity of Grade 2 and Grade 3. Only grade 2 and grade 3 infections occurring post transplantation were reported on the study. Grade 2 and grade 3 infections are defined by the BMT CTN Technical MOP. Higher infection grade indicates worse infection severity. The infection grading criteria are published online (https://bmtctn.net/administrative-manual-procedures-moppolicy-guidelines). Severity of grade 1, 2 and 3 are described for bacterial, fungal, viral, parasitic, and nonmicrobiological infections. For example, grade 2 fungal infections are defined as candida esophagitis, or proven or probably fungal sinusistis confirmed radiologically without orbital, brain or bone involvement. Grade 3 fungal infections are defined as Fungemia including candidemia, Proven or probably invasive fungal infections, Disseminated infections with histoplasmosis, blastomycosis, coccidiomycosis, or Cryptococcus, or Pneumocystis jiroveci pneumonia. |
| Frequencies of Infections Categorized by Infection Type | 1 Year | The number of systemic infections is reported. Infections are categorized by infection type. A participant can report multiple types of infections, so the categories are not mutually exclusive for participants. All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation were reported on the study. |
| Percentage of Participants With Cytomegalovirus (CMV), Epstein Barr Virus (EBV) or Post-Transplant Lymphoproliferative Disease (PTLD) | 1 Year | CMV viremia and disease, EBV viremia, and PTLD are monitored and reported per protocol. The cumulative percentage of each outcome was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to event treated as a competing risk. |
| Participants With Grade 3-5 Toxicities by SOC | 1 Year | Toxicities are evaluated for the study participants at Day 28, Day 56, Day 100, Day 180 and Day 365 post-transplant and graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3-5 toxicities are reported with higher grade indicating worse outcomes. Toxicities are summarized here by system organ class (SOC). A participant can report multiple toxicities, so the categories are not mutually exclusive for participants. |
| Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | Baseline, Day 100, 6 Months, and 1 Year | HR-QoL will be measured using patient reported surveys at baseline and then at Day 100, Day 180, and Day 365 post-transplant. The MOS SF-36 is used for adult participants (\> 18 years). MOS SF-36 is a 36-item general assessment of HR-QoL with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health Index. Each domain is positively scored with higher scores associated with positive outcome. The scale is 0 to 100 where 0 is maximum disability and 100 is no disability. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were used as the outcome measures in summarizing the SF-36 data for this study. These two summaries have the same score scale and Interpretation. |
| Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | Baseline, Day 100, 6 Months, and 1 Year | HR-QoL will be measured using patient reported surveys at baseline and then at Day 100, Day 180, and Day 365 post-transplant. The PedsQL Stem Cell Transplant Module for pediatric participants (8 years through 18 years). The PedsQL Stem Cell Transplant Module is a 46-item instrument that measures HR-QoL in children and adolescents undergoing hematopoietic stem cell transplant, and is developmentally appropriate for self-report in ages 8 through 18 years. The score ranges from 0 to 100 with higher scores associated with positive outcome. |
Countries
United States
Contacts
STUDY_DIRECTORMary Horowitz, MD, MS
Center for International Blood and Marrow Transplant Research
Participant flow
Recruitment details
Participants were recruited from 14 centers between May 2017 and August 2020. The study opened to accrual on May 19, 2017 with 26 centers activated for enrollment. The study closed to accrual on August 31, 2020 and study completed on August 17, 2021. The study was initially designed to enroll participants into Unrelated Cord Blood and Haploidentical cohorts. Due to lack of accrual, the Unrelated Cord Blood cohort was closed for accrual per DSMB recommendation with no patients enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Haplo Bone Marrow HSCT Patients will be treated with a preparative regimen of Antithymocyte Globulin (ATG) (4.5 mg/kg), fludarabine (150 mg/m\^2), cyclophosphamide (29 mg/kg), and low dose total body irradiation (TBI) (200 cGy) before undergoing the haplo HSCT. GVHD prophylaxis will be with post-HSCT cyclophosphamide (100 mg/kg), tacrolimus, and mycophenolate mofetil (MMF). G-CSF will be administered post-transplant.
Antithymocyte Globulin (ATG): Administration of ATG will be 0.5 mg/kg IV on Day -9 over 6 hours and 2 mg/kg IV on Days -8 and -7 over 4 hours.
Fludarabine: Fludarabine dose will be 30 mg/m\^2 IV daily for 5 days from Day -6 to Day -2.
Cyclophosphamide: Cyclophosphamide dose will be 14.5 mg/kg IV daily for 2 days (Day -6 to Day -5) prior to transplantation and 50 mg/kg IV daily for 2 days (Day +3 to Day +4) after transplantation.
Total Body Irradiation (TBI): TBI is to be delivered in a single dose of 200 cGy on Day -1.
Haplo HSCT: Eligible patients without a fully matched related or unrelated donor available will undergo haploidentical bone marrow transplant.
Tacrolimus: Tacrolimus should be started on Day +5 and administered to maintain a level of 10-15 ng/mL.
Mycophenolate mofetil (MMF): MMF dose will be 15 mg/kg PO three times a day (TID) up to 1 gm TID (or IV equivalent) starting on Day +5.
G-CSF: G-CSF will be given IV or SQ starting on Day +5 at 5 mcg/kg/day until ANC is \> 1500 for 3 days. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Haplo Bone Marrow HSCT |
|---|---|
| Age, Continuous | 31.3 years STANDARD_DEVIATION 23.2 |
| CD34 Count | 213.8 x10^6 cells STANDARD_DEVIATION 139.2 |
| CD34 Count per kg Recipient Body Weight | 4.7 × 10^6 cells/kg STANDARD_DEVIATION 2.7 |
| CD3 Count | 862.0 cells/uL STANDARD_DEVIATION 631.5 |
| CD3 Count per kg Recipient Body Weight | 21.9 cells/uL per kg STANDARD_DEVIATION 20.3 |
| Creatinine clearance level | 100.9 mL/min STANDARD_DEVIATION 36.2 |
| Donor age | 37.9 years STANDARD_DEVIATION 10.8 |
| Donor Blood Type A- | 1 Participants |
| Donor Blood Type A+ | 10 Participants |
| Donor Blood Type AB+ | 1 Participants |
| Donor Blood Type B+ | 6 Participants |
| Donor Blood Type Missing | 2 Participants |
| Donor Blood Type O- | 2 Participants |
| Donor Blood Type O+ | 9 Participants |
| Donor Ethnicity Hispanic or Latino | 6 Participants |
| Donor Ethnicity Not Hispanic or Latino | 25 Participants |
| Donor gender Female | 18 Participants |
| Donor gender Male | 13 Participants |
| Donor Race Asian | 4 Participants |
| Donor Race Black or African American | 7 Participants |
| Donor Race Hawaiian/Pacific Islander | 1 Participants |
| Donor Race Unknown | 3 Participants |
| Donor Race White | 16 Participants |
| Donor relationship | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Interval from Diagnosis to Transplant | 23.8 months STANDARD_DEVIATION 26.5 |
| Lansky/Karnofsky Performance Score 100 | 5 Participants |
| Lansky/Karnofsky Performance Score 70 | 5 Participants |
| Lansky/Karnofsky Performance Score 80 | 8 Participants |
| Lansky/Karnofsky Performance Score 90 | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 16 Participants |
| RBC Count | 2.7 million/uL STANDARD_DEVIATION 0.4 |
| Recipient Blood Type A- | 3 Participants |
| Recipient Blood Type A+ | 8 Participants |
| Recipient Blood Type AB- | 1 Participants |
| Recipient Blood Type AB+ | 3 Participants |
| Recipient Blood Type B+ | 5 Participants |
| Recipient Blood Type Missing | 1 Participants |
| Recipient Blood Type O+ | 10 Participants |
| Recipient-to-Donor HLA Match Scores 4/8 | 18 Participants |
| Recipient-to-Donor HLA Match Scores 5/8 | 8 Participants |
| Recipient-to-Donor HLA Match Scores 6/8 | 3 Participants |
| Recipient-to-Donor HLA Match Scores 7/8 | 2 Participants |
| Serum Bilirubin level | 0.8 mg/dL STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
| TNC count | 204.9 x10^8 cells STANDARD_DEVIATION 93.3 |
| TNC per kg Recipient Body Weight | 4.4 × 10^8 cells/kg STANDARD_DEVIATION 1.7 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 1 / 32 |
Outcome results
Primary
Percentage of Participants With Overall Survival (OS)
Overall survival (OS) is the primary endpoint of this study. The time to this event is the time from transplant to death from any cause or last follow-up or 1 year from transplant, whichever occurs first. The one-year OS probability and its 95% confidence interval were estimated using the Kaplan-Meier estimator and Greenwood's formula.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Overall Survival (OS) | 80.6 percentage of participants |
Secondary
Frequencies of Infections Categorized by Infection Type
The number of systemic infections is reported. Infections are categorized by infection type. A participant can report multiple types of infections, so the categories are not mutually exclusive for participants. All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation were reported on the study.
Time frame: 1 Year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Frequencies of Infections Categorized by Infection Type | Bacterial infection | 26 infections |
| Haplo Bone Marrow HSCT | Frequencies of Infections Categorized by Infection Type | Viral infection | 32 infections |
| Haplo Bone Marrow HSCT | Frequencies of Infections Categorized by Infection Type | Fungal infection | 3 infections |
| Haplo Bone Marrow HSCT | Frequencies of Infections Categorized by Infection Type | Protozoal infection | 0 infections |
| Haplo Bone Marrow HSCT | Frequencies of Infections Categorized by Infection Type | Other infection | 3 infections |
Secondary
Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36)
HR-QoL will be measured using patient reported surveys at baseline and then at Day 100, Day 180, and Day 365 post-transplant. The MOS SF-36 is used for adult participants (\> 18 years). MOS SF-36 is a 36-item general assessment of HR-QoL with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health Index. Each domain is positively scored with higher scores associated with positive outcome. The scale is 0 to 100 where 0 is maximum disability and 100 is no disability. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were used as the outcome measures in summarizing the SF-36 data for this study. These two summaries have the same score scale and Interpretation.
Time frame: Baseline, Day 100, 6 Months, and 1 Year
Population: Analysis Population includes transplanted adult participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS at Baseline | 37.9 score on a scale | Standard Deviation 7.9 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS at Day 100 | 41.8 score on a scale | Standard Deviation 11.6 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS at 6 Months | 44.3 score on a scale | Standard Deviation 9.9 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS at 1 Year | 47.5 score on a scale | Standard Deviation 8.1 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS Change at Day 100 from baseline | 4 score on a scale | Standard Deviation 13.8 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS Change at 6 Months from baseline | 6.6 score on a scale | Standard Deviation 11.6 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | PCS Change at 1 Year from baseline | 10.4 score on a scale | Standard Deviation 6.6 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS at Baseline | 45.7 score on a scale | Standard Deviation 13.2 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS at Day 100 | 49.4 score on a scale | Standard Deviation 14.2 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS at 6 Months | 50.4 score on a scale | Standard Deviation 11.2 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS at 1 Year | 48.6 score on a scale | Standard Deviation 14.9 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS Change at Day 100 from baseline | 4.8 score on a scale | Standard Deviation 14 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS Change at 6 Months from baseline | 6 score on a scale | Standard Deviation 10.2 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - Medical Outcomes Study Short Form (MOS SF-36) | MCS Change at 1 Year from baseline | 2.2 score on a scale | Standard Deviation 10.7 |
Secondary
Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module
HR-QoL will be measured using patient reported surveys at baseline and then at Day 100, Day 180, and Day 365 post-transplant. The PedsQL Stem Cell Transplant Module for pediatric participants (8 years through 18 years). The PedsQL Stem Cell Transplant Module is a 46-item instrument that measures HR-QoL in children and adolescents undergoing hematopoietic stem cell transplant, and is developmentally appropriate for self-report in ages 8 through 18 years. The score ranges from 0 to 100 with higher scores associated with positive outcome.
Time frame: Baseline, Day 100, 6 Months, and 1 Year
Population: Analysis Population includes transplanted pediatric participants. Four participants are under age 8 and not eligible for PedsQL assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL at Baseline | 72.8 score on a scale | Standard Deviation 13.6 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL at Day 100 | 86.5 score on a scale | Standard Deviation 15.4 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL at 6 Months | 84.4 score on a scale | Standard Deviation 12.5 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL at 1 Year | 93.3 score on a scale | Standard Deviation 6.9 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL Change at Day 100 from baseline | 11.4 score on a scale | Standard Deviation 16.2 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL Change at 6 Months from baseline | 9.5 score on a scale | Standard Deviation 15.4 |
| Haplo Bone Marrow HSCT | Health Related Quality of Life (HR-QoL) - PedsQL Stem Cell Transplant Module | PedsQL Change at 1 Year from baseline | 18.7 score on a scale | Standard Deviation 11.1 |
Secondary
Immune Reconstitution of Flow Cytometry
Quantitative assessments of peripheral blood CD3, CD4, CD8, CD19, and CD56 positive lymphocytes will be done through flow cytometric analysis.
Time frame: Baseline, Days 100, 180, and 365
Population: Analysis Population includes transplanted participants with available data at each time point. All transplanted participants contribute data for this endpoint assessment, but not all participants provided all subsets of immune reconstitution data at each assessment time point. Only participants who had immune reconstitution results are assessed at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD8 at Day 100 | 272.9 cells/uL | Standard Deviation 318.5 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD3 at Baseline | 862 cells/uL | Standard Deviation 631.5 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD3 at Day 100 | 550.8 cells/uL | Standard Deviation 844.1 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD3 at 6 Months | 640.5 cells/uL | Standard Deviation 662.4 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD3 at 1 Year | 1121 cells/uL | Standard Deviation 808.3 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD4 at Baseline | 434.1 cells/uL | Standard Deviation 323.3 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD4 at Day 100 | 122.3 cells/uL | Standard Deviation 123.1 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD4 at 6 Months | 172.6 cells/uL | Standard Deviation 119.8 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD4 at 1 Year | 472.7 cells/uL | Standard Deviation 365.6 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD8 at Baseline | 326.9 cells/uL | Standard Deviation 274.8 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD8 at 6 Months | 333.3 cells/uL | Standard Deviation 409.1 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD8 at 1 Year | 569.7 cells/uL | Standard Deviation 616.7 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD19 at Baseline | 106.2 cells/uL | Standard Deviation 159.9 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD19 at Day 100 | 221.1 cells/uL | Standard Deviation 477.2 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD19 at 6 Months | 204.8 cells/uL | Standard Deviation 173.4 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD19 at 1 Year | 264.6 cells/uL | Standard Deviation 222.3 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD56 at Baseline | 124.6 cells/uL | Standard Deviation 186.5 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD56 at Day 100 | 237.6 cells/uL | Standard Deviation 232.5 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD56 at 6 Months | 260.3 cells/uL | Standard Deviation 228.6 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Flow Cytometry | CD56 at 1 Year | 293.2 cells/uL | Standard Deviation 300.2 |
Secondary
Immune Reconstitution of Quantitative Immunoglobulins
Quantitative immunoglobulins of IgA, IgG, IgM were done at baseline and 1-year post-transplant.
Time frame: baseline and 1-year
Population: Analysis Population includes transplanted participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgA at Baseline | 172.3 mg/dL | Standard Deviation 92.7 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgA at 1 Year | 111.6 mg/dL | Standard Deviation 52.1 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgG at Baseline | 987.5 mg/dL | Standard Deviation 343.2 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgG at 1 Year | 1004 mg/dL | Standard Deviation 521.9 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgM at Baseline | 102.8 mg/dL | Standard Deviation 48.4 |
| Haplo Bone Marrow HSCT | Immune Reconstitution of Quantitative Immunoglobulins | IgM at 1 Year | 96 mg/dL | Standard Deviation 85.2 |
Secondary
Number of Participants Experiencing Chronic GVHD With Maximum Severity
The event for this secondary endpoint is any chronic GVHD based on 2014 NIH Consensus Criteria. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD will also be recorded. The overall chronic GVHD severity is based on the eight organs score. The maximin severity level of chronic GVHD include mild, moderate and severe.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Number of Participants Experiencing Chronic GVHD With Maximum Severity | None | 23 Participants |
| Haplo Bone Marrow HSCT | Number of Participants Experiencing Chronic GVHD With Maximum Severity | Mild | 7 Participants |
| Haplo Bone Marrow HSCT | Number of Participants Experiencing Chronic GVHD With Maximum Severity | Moderate | 1 Participants |
| Haplo Bone Marrow HSCT | Number of Participants Experiencing Chronic GVHD With Maximum Severity | Severe | 0 Participants |
Secondary
Participants Alive With Autologous Recovery
Autologous recovery is defined as ANC \> 0.5 x 10\^9/L and transfusion independence but with \< 5% donor chimerism (whole blood or m. arrow). This endpoint was reviewed and adjudicated by ERC. The analysis is based on ERC data.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Participants Alive With Autologous Recovery | Yes, alive with autologous recovery | 0 Participants |
| Haplo Bone Marrow HSCT | Participants Alive With Autologous Recovery | No, Death | 6 Participants |
| Haplo Bone Marrow HSCT | Participants Alive With Autologous Recovery | No, Alive but not auto recovery | 25 Participants |
Secondary
Participants Alive With Sustained Engraftment
Being alive and engrafted is defined as not having experienced death, primary graft failure, or secondary graft failure. Donor cell engraftment is defined as donor chimerism greater than or equal to 5% on or after Day 56 after transplantation. Chimerism may be evaluated in whole blood or blood cell fractions, including CD3 and CD33 or CD15 fractions. For this protocol, lineage-specific, myeloid, and T cell chimerisms are required. This endpoint was adjudicated by the Endpoint Review Committee (ERC) and ERC data was used for the analysis.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Participants Alive With Sustained Engraftment | Yes, alive and engrafted | 24 Participants |
| Haplo Bone Marrow HSCT | Participants Alive With Sustained Engraftment | Primary graft failure | 4 Participants |
| Haplo Bone Marrow HSCT | Participants Alive With Sustained Engraftment | Secondary graft failure | 1 Participants |
| Haplo Bone Marrow HSCT | Participants Alive With Sustained Engraftment | Death without graft failure | 2 Participants |
Secondary
Participants With Grade 3-5 Toxicities by SOC
Toxicities are evaluated for the study participants at Day 28, Day 56, Day 100, Day 180 and Day 365 post-transplant and graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3-5 toxicities are reported with higher grade indicating worse outcomes. Toxicities are summarized here by system organ class (SOC). A participant can report multiple toxicities, so the categories are not mutually exclusive for participants.
Time frame: 1 Year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Abnormal Liver Symptoms | 7 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Blood and Lymphatic Disorders | 1 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Cardiovascular Disorders | 15 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Chemistry/Investigations | 2 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | GI Disorders | 10 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | General Disorders | 5 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Hemorrhagic Disorders | 3 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Hepatic Disorders | 6 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Immune System Disorders | 1 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Metabolism and Nutrition Disorders | 7 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Musculoskeletal and Connective Tissue Disorders | 1 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Nervous System Disorders | 4 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Renal Disorders | 5 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Respiratory, Thoracic and Mediastinal Disorders | 8 Participants |
| Haplo Bone Marrow HSCT | Participants With Grade 3-5 Toxicities by SOC | Total (any of above SOC) | 23 Participants |
Secondary
Participants With Infections of Maximum Grade 2 and Grade 3
Number of participants who reported the Maximum Infection Severity of Grade 2 and Grade 3. Only grade 2 and grade 3 infections occurring post transplantation were reported on the study. Grade 2 and grade 3 infections are defined by the BMT CTN Technical MOP. Higher infection grade indicates worse infection severity. The infection grading criteria are published online (https://bmtctn.net/administrative-manual-procedures-moppolicy-guidelines). Severity of grade 1, 2 and 3 are described for bacterial, fungal, viral, parasitic, and nonmicrobiological infections. For example, grade 2 fungal infections are defined as candida esophagitis, or proven or probably fungal sinusistis confirmed radiologically without orbital, brain or bone involvement. Grade 3 fungal infections are defined as Fungemia including candidemia, Proven or probably invasive fungal infections, Disseminated infections with histoplasmosis, blastomycosis, coccidiomycosis, or Cryptococcus, or Pneumocystis jiroveci pneumonia.
Time frame: 1 Year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Participants With Infections of Maximum Grade 2 and Grade 3 | None | 12 Participants |
| Haplo Bone Marrow HSCT | Participants With Infections of Maximum Grade 2 and Grade 3 | Grade 2 | 12 Participants |
| Haplo Bone Marrow HSCT | Participants With Infections of Maximum Grade 2 and Grade 3 | Grade 3 | 7 Participants |
Secondary
Participants With Maximum Acute GVHD
Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). Acute GVHD grading is performed by the consensus conference criteria (Przepiorka et al. 1995) with higher grade indicating worse outcomes. Grade I acute GVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-4 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver. Maximum grade of acute GVHD through 100 days post transplant is reported.
Time frame: Day 100
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Participants With Maximum Acute GVHD | None | 23 Participants |
| Haplo Bone Marrow HSCT | Participants With Maximum Acute GVHD | Grade I | 3 Participants |
| Haplo Bone Marrow HSCT | Participants With Maximum Acute GVHD | Grade II | 5 Participants |
| Haplo Bone Marrow HSCT | Participants With Maximum Acute GVHD | Grade III | 0 Participants |
| Haplo Bone Marrow HSCT | Participants With Maximum Acute GVHD | Grade IV | 0 Participants |
Secondary
Percentage of Participants With Acute Graft-vs-host-disease (GVHD)
Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). Acute GVHD is graded by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The time of onset of grades II-IV and grades III-IV acute GVHD were recorded. This endpoint is evaluated through 100 days post-transplant. Cumulative percentage of acute GVHD post-transplant are estimated using the cumulative incidence function, treating death prior to acute GVHD as the competing risk.
Time frame: Day 100
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Acute Graft-vs-host-disease (GVHD) | 16.1 percentage of participants |
Secondary
Percentage of Participants With Chronic GVHD
The event for this secondary endpoint is any chronic GVHD based on 2014 NIH Consensus Criteria. This includes mild, moderate and severe chronic GVHD. The analyses of Chronic GVHD use the site-reported data. The cumulative percentage of chronic GVHD is computed using the cumulative incidence function, treating death prior to chronic GVHD as a competing risk. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD will also be recorded. This secondary endpoint of chronic GVHD will include mild, moderate and severe chronic GVHD based on NIH Consensus Criteria.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Chronic GVHD | 25.8 percentage of participants |
Secondary
Percentage of Participants With Cytomegalovirus (CMV), Epstein Barr Virus (EBV) or Post-Transplant Lymphoproliferative Disease (PTLD)
CMV viremia and disease, EBV viremia, and PTLD are monitored and reported per protocol. The cumulative percentage of each outcome was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to event treated as a competing risk.
Time frame: 1 Year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Cytomegalovirus (CMV), Epstein Barr Virus (EBV) or Post-Transplant Lymphoproliferative Disease (PTLD) | Cumulative Percentage of Participants with EBV | 9.7 percentage of participants |
| Haplo Bone Marrow HSCT | Percentage of Participants With Cytomegalovirus (CMV), Epstein Barr Virus (EBV) or Post-Transplant Lymphoproliferative Disease (PTLD) | Cumulative Percentage of Participants with CMV | 22.6 percentage of participants |
| Haplo Bone Marrow HSCT | Percentage of Participants With Cytomegalovirus (CMV), Epstein Barr Virus (EBV) or Post-Transplant Lymphoproliferative Disease (PTLD) | Cumulative Percentage of Participants with PTLD | 6.5 percentage of participants |
Secondary
Percentage of Participants With Graft-Failure-Free Survival
Events for Graft-Failure-Free Survival (GFFS) including death, primary graft failure, secondary graft failure. The time to this event is the time from transplant to death from any cause, or graft failure, or last follow-up, or 1 year from transplant, whichever occurs first. For patients experiencing primary graft failure, Day 0.1 was used for primary graft failure event date to count the event in. The one-year GFFS probability and its 95% confidence interval were estimated using the Kaplan-Meier estimator and Greenwood's formula.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Graft-Failure-Free Survival | 77.4 percentage of participants |
Secondary
Percentage of Participants With Neutrophil Recovery
Neutrophil recovery is achieving an absolute neutrophil count (ANC) \> 0.5 x10\^9/L for three consecutive measurements on different days, with the first of the three days being defined as the day of neutrophil engraftment. The cumulative percentage of neutrophil engraftment was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to neutrophil engraftment treated as a competing risk.
Time frame: Day 28 and 56
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Neutrophil Recovery | Day 28 | 93.5 percentage of participants |
| Haplo Bone Marrow HSCT | Percentage of Participants With Neutrophil Recovery | Day 56 | 93.5 percentage of participants |
Secondary
Percentage of Participants With Platelet Recovery
Platelet recovery is defined by achieving a platelet count \> 20 x 10\^9/L with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be defined as the day of platelet engraftment. The cumulative percentage of platelet engraftment was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to platelet engraftment treated as a competing risk.
Time frame: Day 100
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Platelet Recovery | 77.4 percentage of participants |
Secondary
Percentage of Participants With Primary Graft Failure
Primary graft failure is defined by the lack of neutrophil engraftment by Day 56 post-HSCT or failure to achieve at least 5% donor chimerism (whole blood or marrow) on any measurements up to and including Day +56. For this protocol, lineage-specific, myeloid, and T cell chimerisms are required. Myeloid engraftment might not proceed at the same rate as T cell engraftment. If myeloid has greater than or equal to 5% donor, even if T cell compartment does not, this is not considered primary graft failure. Secondary graft failure is defined by initial neutrophil engraftment (ANC greater than or equal to 0.5 x 10\^8/L measured for 3 consecutive measurements on different days) followed by sustained subsequent decline in ANC to less than 0.5 x 10\^9/L for three consecutive measurements on different days or initial whole blood or marrow donor chimerism greater than or equal to 5%, but then declining to less than 5% on subsequent measurements or second infusion/transplant given for graft failure.
Time frame: Day 56
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Primary Graft Failure | 12.9 percentage of participants |
Secondary
Percentage of Participants With Secondary Graft Failure
Secondary graft failure is defined as any one of the following: 1. Initial neutrophil engraftment (ANC greater than or equal to 0.5 x10\^9/L measured for three consecutive measurements on different days) followed by sustained subsequent decline in ANC to less than 0.5 x 10\^9/L for three consecutive measurements on different days; 2. Initial whole blood or marrow donor chimerism greater than or equal to 5%, but then declining to less than 5% on subsequent measurements; 3. Second infusion/transplant given after Day 56 for graft failure.
Time frame: 1 year
Population: Analysis Population includes transplanted participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Haplo Bone Marrow HSCT | Percentage of Participants With Secondary Graft Failure | 3.2 percentage of participants |