Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders

Eligibility Criteria

• * Complete first remission (CR1) at high risk for relapse such as any of the following:
• * Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder (MPS).
• * Therapy-related AML (t-AML).
• * White cell count at presentation \> 100,000.
• * Presence of extramedullary leukemia at diagnosis.
• * Any unfavorable subtype by FAB or WHO classification.
• * High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, complex karyotype) or high-risk molecular abnormalities.
• * Requirement for 2 or more inductions to achieve CR1.
• * Presence of Minimal Residual Disease (MRD+) by cytogenetics, flow cytometry or molecular methods after induction.
• * Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy.
• * Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician.
• * Other high-risk features not defined above.
• * Complete second remission (CR2).
• * Primary refractory or relapsed AML with less than 10% blasts by bone marrow morphology. Patients with cytogenetic, flow cytometric, or molecular abnormalities in ≤ 10% of cells are eligible.
• * Complete first remission (CR1) at high risk for relapse such as any of the following:
• * White cell count at presentation \> 30,000 for B-cell lineage and \> 100,000 for T-cell lineage.
• * Presence of any high-risk cytogenetic abnormalities such as t (9;22), t (1;19), t (4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality.
• * Failure to achieve complete remission (CR) after four weeks of induction therapy.
• * Persistence or recurrence of MRD on therapy.
• * Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.
• * Other high-risk features not defined above.
• * Complete second remission (CR2).
• * Primary refractory or relapsed ALL with MRD disease after antibody therapy (e.g., blinatumomab, inotuzumab, other) and/or CAR-T cell therapy.
• * International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis.
• * Any IPSS risk category if life-threatening cytopenia(s) exists.
• * Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia.
• * MDS/ myeloproliferative disorder overlap syndromes without myelofibrosis.
• * MDS/ MPD patients must have less than 10% bone marrow myeloblasts and ANC ≥ 0.2 (growth factor supported if necessary) at transplant work-up.
• * Eligible patients with aggressive histology (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histology) in CR.
• * Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2nd or subsequent progression with stable disease/ CR/ PR with no single lesion equal to or more than 5 cm.
• * Eligible patients with HL will be those without progression of disease (POD) after salvage chemotherapy with no single lesion ≥ 5 cm.
• * Hurler Syndrome
• * Hunter (MPS 2 - early disease)
• * Sly syndrome (MPSVIII)
• * α-Mannosidosis
• * X- ALD
• * Osteopetrosis
• * Metachromatic Leukodystrophy
• * Globoid (GLD)
• * Hemoglobinopathies
• * Bone Marrow Failure syndromes
• * Immunodeficiencies, including HLH
• * Karnofsky or Lansky score ≥ 70% (see Appendix)
• * Bilirubin ≤ 1.5 mg/dL (unless benign congenital hyperbilirubinemia).
• * ALT ≤ 3 x upper limit of normal.
• * Pulmonary function (spirometry and corrected DLCO) ≥ 50% predicted (corrected for hemoglobin) .
• * Left ventricular ejection fraction ≥ 50%.
• * Age-adjusted Hematopoietic Cell Transplantation-Comorbidity Index (aaHCT-CI) less than or equal to 7.
• * Renal: serum creatinine ≤ 1.5x normal for age. If serum creatinine is outside the normal range, then CrCl \> 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) \>30% of predicted normal for age.
• * Each CB unit must be at least 3/8 HLA-matched to the patient considering high-resolution 8-allele HLA typing.
• * For malignant diseases follow MSKCC CBU selection algorithm
• * For non-malignant diseases, CBU will be required to have \> 5 x 107 TNC/kg; high HLA allele level match is preferable
• * Inadequate performance status/ organ function.
• * Advanced metabolic disease (EBMT handbook).
• * Active CNS leukemic involvement.
• * Indolent NHL or Hodgkin lymphoma with progression of disease after most recent salvage chemotherapy.
• * Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
• * Autologous stem cell transplant within the preceding 6 months.
• * Any prior allogeneic stem cell transplant.
• * Active and uncontrolled infection (bacterial/fungal/viral) at time of transplantation.
• * HIV infection.
• * Seropositivity for HTLV-1.
• * Pregnancy or breast feeding.
• * Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.