Combination Chemotherapy Followed By Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Severe Aplastic Anemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia.

OBJECTIVES:

* Determine the incidence and severity of acute toxicity in patients with hematologic malignancies or severe aplastic anemia treated with a non-myeloablative conditioning regimen followed by umbilical cord blood transplantation.
* Determine the incidence and severity of acute and chronic graft-versus-host-disease in patients treated with this regimen.
* Determine the incidence of relapse, disease-free survival, and overall survival of patients treated with this regimen.
* Determine the survival rate at 100 days post-transplantation in patients treated with this regimen.
* Determine the incidence of regimen-related complications (infection, hepatic veno-occlusive disease, and interstitial pneumonitis) in patients treated with this regimen.
* Determine the incidence of primary and secondary graft failure in patients treated with this regimen.
* Determine the rates and kinetics of donor-derived lymphoid, myeloid, neutrophil, RBC, and platelet engraftment in patients treated with this regimen.

OUTLINE: Patients receive a non-myeloablative conditioning regimen comprising fludarabine IV over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1. Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.

Patients undergo multiple unit umbilical cord blood transplantation on days 0-1. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.

Patients are followed monthly for 6 months; at 9, 12, 14, 16, 18, and 24 months; and then annually thereafter.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* One of the following histologically confirmed diagnoses:

  * Acquired severe aplastic anemia

    * Meets at least 2 of the following criteria:

      * Granulocyte count less than 500/mm\^3
      * Platelet count less than 20,000/mm\^3
      * Absolute reticulocyte count less than 20,000/mm\^3 (after correction for hematocrit)
    * Unresponsive to OR recurrent disease after prior treatment with anti-thymocyte globulin and/or cyclosporine
  * Acute myeloid leukemia (AML), meeting 1 of the following criteria:

    * Failed induction therapy
    * In first complete remission (CR) with any of the following high-risk features:

      * Stem cell or biphenotype classification (M0)
      * Erythroleukemia (M6)
      * Acute megakaryocytic leukemia (M7)
      * Cytogenetic markers indicative of poor prognosis
      * t(15;17) translocation and failed first-line induction therapy OR there is molecular evidence of persistent disease
      * t(8;21) and inv(16) translocations and failed first-line induction therapy
    * In early relapse\*
    * In second or subsequent remission
    * Recurrent disease after prior autologous stem cell transplantation (SCT) NOTE: \*No refractory relapse
  * Acute lymphoblastic leukemia, meeting 1 of the following criteria:

    * In early relapse\*
    * In second or subsequent remission
    * In first CR with the following high-risk features:

      * t(4;11) or t(9;22) translocation
      * Hyperleukocytosis (initial WBC greater than 30,000/mm\^3)
      * Failed to achieve CR by day 28 of standard induction therapy
    * Recurrent disease after prior autologous SCT NOTE: \*No refractory relapse
  * Chronic myelogenous leukemia

    * Chronic or accelerated phase that has failed medical management
    * Blastic phase allowed after reinduction chemotherapy induces chronic phase
  * Myelodysplastic syndromes meeting 1 of the following criteria:

    * Refractory to medical management
    * Presence of cytogenetic abnormalities predictive of transformation to acute leukemia, including the following:

= 5q- = 7q-

* Monosomy 7 and trisomy 8
* Evidence of evolution to AML (e.g., refractory anemia with excess blasts \[RAEB\], or RAEB in transformation)

  * Chronic lymphocytic leukemia

    * Refractory to treatment including fludarabine-based therapy
    * Recurrent disease after prior autologous SCT
  * Multiple myeloma

    * Recurrent disease after prior autologous SCT
    * Beyond first CR or failed induction therapy
    * Disease is sensitive to pretransplantation cytoreduction
  * Hodgkin's lymphoma

    * Beyond first CR or failed induction therapy
    * Disease is sensitive to pretransplantation cytoreduction
  * Non-Hodgkin's lymphoma (NHL)

    * Recurrent disease after prior autologous SCT
    * Beyond first CR or failed induction therapy
    * Disease is sensitive to pretransplantation cytoreduction
    * Mantle zone NHL allowed after induction therapy
  * Myeloproliferative disorders

    * Refractory to medical management
    * Allografting required unless grade 3 or greater myelofibrosis by bone marrow biopsy

      * No HLA-matched sibling donor available
      * Ineligible for a myeloablative conditioning regimen due to advanced age (over 55), extensive prior therapy, and/or other comorbidities
      * If under age 55, must meet at least 1 of the following criteria:
  * Received extensive prior therapy
  * Organ toxicity or infection precluding eligibility for allogeneic transplantation with full ablation conditioning

    * Availability of 2-5 umbilical cord blood units that are at least a 4/6 HLA match
    * No active CNS disease
    * No primary or grade 3 or 4 myelofibrosis

PATIENT CHARACTERISTICS:

Age

* Any age

Performance status

* Karnofsky 70-100% (for patients 16 years of age and older)
* Lansky 50-100% (for patients under 16 years of age)

Life expectancy

* At least 3 months

Hematopoietic

* See Disease Characteristics

Hepatic

* ALT/AST less than 4 times normal
* Bilirubin less than 2.0 mg/dL (unless due to hepatic infiltration by primary malignancy)

Renal

* Creatinine clearance greater than 40 mL/min

Cardiovascular

* Shortening fraction or ejection fraction greater than 40% of normal value for age by echocardiogram or radionuclide scan

Pulmonary

* FVC and FEV_1 greater than 60% of predicted
* DLCO greater than 60% of predicted (adult patients)
* Clearance by pulmonologist required if patient cannot perform pulmonary function tests

Other

* Not pregnant or nursing
* No uncontrolled active infection (viral, bacterial, or fungal)
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* More than 3 months since prior autologous stem cell transplantation

Chemotherapy

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* Recovered from prior therapy
* No other concurrent investigational agents that would preclude study participation or increase risk to patient

  * Investigational diagnostic procedures allowed