Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies

Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor. All participants will receive a standard backbone GVHD prophylaxis regimen (tacrolimus and sirolimus) and conditioning (cyclophosphamide/TBI). A risk-adapted approach will be used during conditioning to further minimize the risk of leukemia relapse based on two factors:

• Lymphoid versus myeloid primary disease.
• KIR compatibility between donor and host.

Inclusion criteria

*Age less than or equal to 21 years old

High risk malignancy as follows:

• High-risk ALL in CR1. Examples include, but not limited to: Induction failure or > 1% leukemic lymphoblasts in the bone marrow on remission date;> 0.1% leukemic lymphoblasts in the bone marrow in week 7 of continuation treatment (i.e. before reinduction I); re-emergence of leukemic lymphoblasts by MRD (at any level) in patients previously MRD negative; persistently detectable MRD at lower levels;early T-cell precursor (ETP) ALL.
• High-risk ALL beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
• High-risk de novo AML in CR1.Examples include but are not limited to:evidence of a high-risk genetic abnormality or high-risk MRD features.
• AML beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
• Therapy-related AML.
• MDS, primary or secondary, at any stage.
• NK cell lymphoblastic leukemia in any CR
• Biphenotypic bilineage, or undifferentiated leukemia.
• CML in any phase
• Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
• Non-Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
• Juvenile Myelomonocytic Leukemia (JMML).
• All patients with prior evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
• Has a suitable HLA matched sibling or unrelated volunteer donor available for stem cell donation.A "matched" donor is defined as allele matching at 7/8 to 8/8 HLA loci at A, B, C and DRB1.For the purpose of this study, the term "matched sibling" also refers to an HLA matched family member.
• Does not have any other active malignancy other than the one for which this transplant is indicated.
• Left ventricular ejection fraction > 40%,or shortening fraction > 26%.
• Forced vital capacity (FVC) greater than or equal to 50% of predicted value (corrected for hemoglobin), or if patient is unable to perform pulmonary function testing, pulse oximetry greater than or equal to 92% on room air.
• Creatinine clearance greater than or equal to 70 ml/min/1.73m2
• Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 70.
• Bilirubin less than or equal to 2.5 mg/dL.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than or equal to 5 times upper limit of normal
• Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
• Not lactating.
• Has not had a prior allogeneic HSCT.

Exclusion criteria

• Pregnant and lactating females are excluded from participation as the short and long-term effects of the protocol interventions and infusion on a fetus or a nursing child through breast milk are not entirely known at this time.