Cord blood stem cell transplant with chemotherapy in high-risk blood cancers

Who can take part

• Patients aged 6 months to =< 65 years at time of consent
• Acute myelogenous leukemia (AML):; Complete first remission (CR1), complete second remission (CR2) or greater (CR2+), must have < 5% marrow blasts at the time of transplant; Patients in morphologic remission with persistent cytogenetic, flow cytometric, or molecular aberrations are eligible
• Acute lymphoblastic leukemia (ALL):; Complete first remission (CR1) at high risk for relapse such as any of the following:; 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 MRD- complete remission after induction therapy; Persistence or recurrence of minimal residual disease 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) or greater (CR2+); Note: ALL with less than 5% blasts at time of transplant but persistent cytogenetic, flow cytometric or molecular aberrations are eligible
• Other acute leukemias: Acute leukemias of ambiguous lineage or mixed phenotype with less than 5% blasts. Leukemias in morphologic remission with persistent cytogenetic, flow cytometric or molecular aberrations are eligible
• Chronic Myeloid Leukemia (CML): Excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy
• Myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) other than myelofibrosis:; MDS/MPD overlap syndromes without myelofibrosis; MDS/ MPD patients must have less than 10% bone marrow myeloblasts and absolute neutrophil count (ANC) > 0.2 (growth factor supported if necessary) at transplant work-up
• Non-Hodgkin lymphoma (NHL) at high-risk of relapse or progression if not in remission:; 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 by PET/CT imaging; 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 PR or CR by PET/CT imaging
• Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in morphologic remission
• Only for adult patients, to prevent graft rejection, patients who received only non-lymphodepleting agents for their malignancy (hypomethylating agents, venetoclax, hydroxyurea, TKIs etc.), or patients who received lymphodepleting chemotherapy > 3 months prior to scheduled admission, may receive fludarabine 25 mg/m\^2 daily x 3 days for lymphodepletion 14-42 days (aiming for 2-4 weeks) at the discretion of the principal investigator (PI)
• For patients > 16 years old, Karnofsky score ≥ 70%. For patients =< 16 years old, Lansky score ≥ 50%
• Calculated creatinine clearance > 70 ml/min
• Bilirubin < 1.5 mg/dL (unless benign congenital hyperbilirubinemia or hemolysis)
• Alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
• For patients > 18 years old, pulmonary function (spirometry and corrected diffusing capacity for carbon monoxide [DLCO]) > 60% predicted. For patients =< 18 years old, or any patient unable to perform pulmonary function tests, O2 saturation > 92% on room air
• Left ventricular ejection fraction > 50%
• Albumin > 3.0 g/dL
• For patients > 18 years old, Hematopoietic Cell Transplantation Comorbidity index (HCT-CI) =< 5
• UCB units will be selected according to current umbilical cord blood graft selection algorithm. One or two UCB units may be used to achieve the required cell dose
• The UCB graft is matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. This may include 0-2 antigen mismatches at the A or B or DRB1 loci. Unit selection based on cryopreserved nucleated cell dose and HLA-A, B, DRB1 using intermediate resolution A, B antigen and DRB1 allele typing

Who cannot take part

• Prior checkpoint inhibitors/ blockade in the last 12 months
• Two prior stem cell transplants of any kind
• One prior autologous stem cell transplant within the preceding 12 months
• Prior allogeneic transplantation
• Prior involved field radiation therapy that would preclude safe delivery of 400cGy total body irradiation (TBI) in the opinion of radiation oncology
• Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis
• Active and uncontrolled infection at time of transplantation
• HIV infection
• Patients persistent with central nervous system (CNS) involvement in cerebrospinal fluid (CSF) or CNS imaging at time of screening0
• Inadequate performance status/ organ function
• 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