Donor Stem Cell Transplant in Treating Younger Patients with Hematologic Malignancies or Myelodysplasia

Inclusion Criteria

• Acute lymphoblastic leukemia (ALL) in complete remission (CR) >= 2 or high risk disease in CR1. Marrow must be in morphologic remission (minimal residual disease [MRD] positive [+] acceptable) * The criteria for high-risk ALL in first CR are: ** MLL rearrangement with slow early response [defined as having M2 (5-25% blasts) or M3 (> 25% blasts on bone marrow examination on Day 14 of induction therapy)]; or, ** Hypodiploidy (< 44 chromosomes or DNA index < 0.81); or, ** Induction failure (M3 on Day 29 or, M2/M3 or MRD >= 1% on day 43) ** Persistent minimal residual disease (MRD) of >= 0.01% at the end of consolidation
• Hodgkin’s lymphoma relapse post autologous stem cell transplant
• NHL in CR >= 2. Marrow in morphologic remission if applicable (e.g. Burkitt’s leukemia/lymphoma)
• AML in CR1 if high risk by classification, MRD+ at the end of induction I, or CR >= 2. Bone marrow may show CR (< 5% blasts) or, if chemotherapy refractory disease, < 25% morphologic blasts (M2 marrow). Both primary and secondary AML are eligible
• Chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, second chronic phase after blast crisis (active blast crisis will not be eligible). CML patients must have previously failed therapy with at least two tyrosine kinase inhibitors or are intolerant to TKI
• Myelodysplastic syndrome: Patients with documented pre-leukemia (MDS) at any stage including refractory anemia (RA), refractory anemia with ringed sideroblasts, refractory anemia with excess blasts (RAEB), and RAEB in transformation will be eligible for inclusion
• For subjects having previously received chimeric antigen receptor (CAR-T) cells to treat primary disease, potential subjects must: * Be in remission but have reappearance of B-cell 30 days post-CAR T infusion OR * Be not in remission (CAR-T failure) at 30 days post-CAR T infusion OR * Be 60 days post-CAR T infusion * Have resolved all CAR-T toxicities (except B-cell reappearance) AND * Meet other inclusion and restriction criteria defined
• Patient lacks an human leukocyte antigen (HLA) matched sibling donor
• Meets criteria nonhematopoietic organ function according to Nationwide Children's Hospital (NCH) bone marrow transplant (BMT) standard operating procedures (SOP) 09
• If subjects have received a first HCT, they must be eligible for a second hematopoietic cell transplant (HCT) if their disease has recurred, all other restrictions still apply
• High resolution HLA and KIR typing
• The subject cannot have an active untreated infection. Viremia by polymerase chain reaction (PCR) analysis is not considered an active infection but may require immediate viral prophylaxis. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal therapy and be asymptomatic
• Negative pregnancy test for females >= 11 years of age or post-menarche
• Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator. (Non-childbearing potential defined as pre-menarche, greater than one year post-menopausal or surgically sterilized)
• Subjects must be =< 30 years at the time of consent
• Signed consent by parent/guardian and assent if appropriate for subjects < 18 years of age. Signed consent by patient/subject if >= 18 years of age
• DONOR: The donor must be >= 18 years of age at the time of the informed consent conference
• DONOR: The donor must be a related donor
• DONOR: The donor will be evaluated according to NCH BMT SOP 04 and must meet all criteria
• DONOR: The donor must be able and willing to undergo G-CSF mobilization and stem cell apheresis
• DONOR: The patient does not have donor specific anti-HLA antibodies

Exclusion Criteria

• Patient does not have a suitable donor who is willing and able (meets donor criteria)
• Patient has donor-specific anti-HLA antibodies at the time of enrolment
• Patient reports a history of allergic reactions to murine protein