Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing an Umbilical Cord Blood Transplant for Hematologic Cancer

Inclusion Criteria

• The unrelated cord blood donor(s) must be 4-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution)
• No existing HLA-identical related donor is available
• Suitable UCB units available according to Umbilical Cord Blood Graft selection algorithm; the UCB graft may consist of one or two UCB units
• Acute myeloid leukemia (AML): high risk complete response (CR)1 (as evidenced by preceding myelodysplastic syndromes [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
• Very high risk pediatric patients with AML; patients < 21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
• Acute lymphocytic leukemia (ALL): high risk CR1 as defined by cytogentics (such as t(9;22), t (1:19), t(4;11), other mixed lineage leukemia (MLL) rearrangements, hypodiploidy, or IKZF1 abnormalities), deoxyribonucleic acid (DNA) index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
• Very high risk pediatric patients with ALL; patients < 21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction; they are eligible once they achieved a complete remission
• Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate
• Plasma Cell leukemia after initial therapy, who achieved at least a partial remission
• Advanced myelofibrosis
• Myelodysplasia (MDS) International Prostate Symptom Score (IPSS) Int-2 or High risk (i.e. refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma are eligible if there was disease progression/relapse within 12 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 (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant
• Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+
• Large cell non-Hodgkin's lymphoma (NHL) > CR2/ > PR2; patients in CR2/PR2 with initial short remission (< 6 months) are eligible
• Lymphoblastic lymphoma, Burkitt’s lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year
• Multiple myeloma beyond PR2; patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
• Myeloproliferative syndromes
• Recipients must have a Karnofsky score (adults) >= 80 % or Lansky score >= 50% (pediatrics)
• Creatinine < 2.0 (adults) or creatinine clearance > 40 ml/min (pediatrics)
• Bilirubin, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), alkaline phosphatase (ALP) =< 2 x upper limit of normal
• Diffusion capacity of carbon monoxide (DLCO)corr > 50% normal
• Left ventricular ejection fraction >= 45%
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care

Exclusion Criteria

• Active infection at time of transplantation (including active infection with aspergillus or other mold within 30 days)
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breast feeding; the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• Chemotherapy refractory large cell and high grade NHL (i.e. progressive disease after > 2 salvage regimens)
• If > 18 years old, prior myeloablative transplant within the last 6 months
• If =< 18 years old, prior myeloablative transplant within the last 6 months; if > 18 years old prior myeloablative allotransplant or autologous transplant
• Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
• Patients who have received Y-90 ibritumomab (zevalin) or I-131 tostumomab (bexxar), as part of their salvage therapy are not eligible for myeloablative umbilical cord blood transplant