RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.

OBJECTIVES:

• Determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.
• Determine the incidence of graft-versus-host-disease in this setting.
• Describe the incidence of recurrent disease in these patients post UCB transplant.
• Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.
• Determine specifically whether larger recipients can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.

OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.

Patients are followed at least monthly for 1 year, then every 6 months for the second year, and then annually thereafter.

PROJECTED ACCRUAL: There will be a maximum of 48 patients accrued into this study over 4 years.

• Graft Versus Host Disease
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: anti-thymocyte globulin
• Drug: busulfan
• Drug: cyclosporine
• Drug: melphalan
• Drug: methylprednisolone
• Procedure: umbilical cord blood transplantation
• Radiation: radiation therapy

• Lesniewski ML, Haviernik P, Weitzel RP, Kadereit S, Kozik MM, Fanning LR, Yang YC, Hegerfeldt Y, Finney MR, Ratajczak MZ, Greco N, Paul P, Maciejewski J, Laughlin MJ. Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells. Leukemia. 2008 Dec;22(12):2201-7. Epub 2008 Sep 4.
• van Heeckeren WJ, Fanning LR, Meyerson HJ, Fu P, Lazarus HM, Cooper BW, Tse WW, Kindwall-Keller TL, Jaroscak J, Finney MR, Fox RM, Solchaga L, Forster M, Creger RJ, Laughlin MJ. Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007 Nov;139(3):464-74.
• Weitzel RP, Lesniewski ML, Haviernik P, Kadereit S, Leahy P, Greco NJ, Laughlin MJ. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood. 2009 Jun 25;113(26):6648-57. Epub 2009 Mar 13.

DISEASE CHARACTERISTICS:

• Histologically confirmed high risk malignancy including:

  • Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first complete remission with high risk features including stem cell or biphenotypic classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6), acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor prognosis, or failure to achieve complete remission after standard induction therapy
  • Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission

  • Chronic myeloid leukemia (CML) in chronic phase

    • CML with accelerated phase or blast crisis are eligible after reinduction chemotherapy converts disease to chronic phase
  • High risk ALL in first complete remission

  • Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia

    • Refractory anemia with excess blasts
    • Refractory anemia with excess blasts in transformation
  • Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation

• Must also meet all the following conditions:

  • No HLA-ABC/DR identical related bone marrow or UCB donor
  • No 5/6 antigen matched related bone marrow or UCB donor
  • Condition precludes waiting to search and find a donor in the National Marrow Donor Registry
• Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project
• No active CNS disease

PATIENT CHARACTERISTICS:

Age:

• Under 55 at time of umbilical cord blood transplantation

Performance status:

• Zubrod 0-1
• Karnofsky 80-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without marrow involvement who elect to undergo autologous peripheral blood stem cell collection and storage:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT/AST no greater than 4 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)

Pulmonary:

• FVC and FEV_1 at least 60% of predicted for age

• For adults:

  • DLCO at least 60% of predicted

Other:

• HIV negative
• No active infections at time of autologous stem cell harvest or pretransplant cytoreduction
• Not pregnant or nursing
• Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior autologous stem cell transplantation allowed

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified