Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation with or without Anti-Thymocyte Globulin before Donor Umbilical Cord Blood Transplant in Treating Patients with Hematologic Cancer

Inclusion Criteria

• < 70 years of age with no matched 5/6 or 6/6 sibling donor - patients >= 70 and =< 75 years of age may be eligible if they have a co-morbidity score =< 2
• Karnofsky score >= 70% (>= 16 years) or Lansky score >= 50 (< 16 years)
• UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
• Acute leukemias: Must be in remission by morphology (< 5% blasts); Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
• Acute myeloid leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in =< 60 years old that is NOT considered as favorable-risk; favorable risk AML is defined as having one of the following: * t(8,21) without cKIT mutation * inv(16) or t(16;16) without cKIT mutation * Normal karyotype with mutated NPM1 and wild type FLT-ITD * Normal karyotype with double mutated CEBPA * Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
• Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following: * Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1 * 30 years of age or older at diagnosis * White blood cell counts of greater than 30,000/mcL (B cell [B]-ALL) or greater than 100,000/mcL (T cell [T]-ALL) at diagnosis * Central nervous system (CNS) leukemia involvement during the course of disease * Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy) * Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
• Biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent CR
• Chronic myelogenous leukemia in chronic or accelerated phase, or chronic myelogenous leukemia (CML) blast crisis in morphological remission (< 5% blasts): chronic phase patients must have failed at least two tyrosine kinase inhibitors been intolerant to all available tyrosine kinase inhibitors (TKIs) or have T315I mutation
• Myelodysplastic syndrome: International Prognostic Scoring System (IPSS) interleukin-2 (INT-2) or high risk; revised (R)-IPSS high or very high; World Health Organization (WHO) classification: refractory anemia with excess blasts (RAEB)-1, RAEB-2; severe cytopenias: absolute neutrophil count (ANC) < 0.8, anemia or thrombocytopenia requiring transfusion; poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS; blasts must be < 5% by bone marrow aspirate morphology; if >= 5% blasts, patient requires chemotherapy for cytoreduction to < 5% blasts prior to transplantation
• Minimal residual disease (MRD) positive leukemia (AML, ALL or accelerated/blast phase CML); selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status
• Leukemia or MDS in aplasia; these patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease >= 28 days post-therapy; these high risk patients will be analyzed separately
• Burkitt’s lymphoma in CR2 or subsequent CR
• Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/partial remission (PR) that has failed or ineligible for an autologous transplant
• Natural killer cell malignancies
• Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant
• Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed within 12 months of achieving a partial or complete remission; patients who had remissions lasting > 12 months, are eligible after at least two prior therapies; patients with bulky disease should be considered for debulking chemotherapy before transplant; patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month
• Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive
• Relapsed multiple myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
• Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
• Acquired bone marrow failure syndromes, except for Fanconi anemia
• Myeloproliferative neoplasms/myelofibrosis
• Additional criteria for bulky disease (lymphomas): *If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately) *If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction >= 40%; for children that are not able to cooperate with multi-gated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician’s note
• Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) >= 40% predicted, and absence of oxygen (O2) requirements; for children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted; if neither test can be obtained it should be clearly stated in the physician’s note
• Transaminases =< 5 x upper limit of normal (ULN) and total bilirubin =< 2.5 mg/dL except for patients with Gilbert’s syndrome or hemolysis
• Creatinine =< 2.0 mg/dl (adults) and creatinine clearance >= 40 mL/min (pediatrics); adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated creatinine clearance >= 40 ml/min/1.73m^2
• Adequate performance status is defined as Karnofsky score >= 70% (>= 16 years of age) or Lansky score >= 50 (pediatrics)
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

Exclusion Criteria

• Pregnant or breast feeding; females of childbearing potential must have a negative pregnancy test prior to starting therapy
• Untreated active infection
• Active human immunodeficiency virus (HIV) infection or known HIV positive serology
• Less than 3 months since prior myeloablative transplant
• Evidence of progressive disease by imaging modalities or biopsy - persistent positron emission tomography (PET) activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of computed tomography (CT) changes indicating progression
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy
• Active central nervous system malignancy