Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies
This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is \< 18%.
• Patient age 0.5-25years
• Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
• An unrelated donor search is not required for a patient to be eligible for this protocol, or a donor search and donor mobilization may be abandoned if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant or a low-likelihood of finding a matched, unrelated donor. Patients with an eligible HLA-matched RELATED should not be enrolled on this trial.
• Patients must have at least one of the following high-risk conditions listed below:
• Acute lymphocytic leukemia (ALL) in CR1\* as defined by at least one of the following:
⁃ hypodiploidy, induction failure,Minimal residual disease (MRD) after consolidation
• Acute myeloid leukemia (AML) in CR1 with high risk features defined as: High allelic ratio FLT3/ITD+, Monosomy 7, Del (5q), Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to Children's Oncology Group (COG) AAML1031 study who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect \> 0.1% blasts)
• Acute Leukemia in 2nd or subsequent CR (CR\>2)
• Mixed phenotype/Undifferentiated Leukemia in 1st or subsequent CR\*
• Secondary or therapy related leukemia in CR \> 1
• Natural Killer (NK) cell lymphoblastic leukemia CR \> 1
• Myelodysplastic syndrome (MDS)
• Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221 study)
• Prior transplant eligible if \< 18yo, \>6 months has elapsed since BMT, and patient is off immunosuppression for \> 3 months with no Graft versus host disease (GVHD)
• No known active Central nervous system (CNS) involvement or extramedullary involvement by malignancy. Such disease treated into remission is permitted.
• Acute Leukemia - Remission is defined as morphology with \< 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with \> 20% cellularity.