Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

OBJECTIVES:

Primary

• Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of > 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

Secondary

• Determine the toxicity of a myeloablative preparative regimen comprising busulfan, fludarabine, and etoposide prior to UCBT in these patients.
• Determine the neutrophil and platelet recovery in patients treated with this regimen.
• Determine the event-free and overall survival of patients treated with this regimen.
• Evaluate lineage-specific chimerism after UCBT and assess the contribution of each individual cord blood unit to post-transplantation hematopoiesis in these patients.
• Determine the incidence, severity, and timing of acute and chronic graft-vs-host disease in patients treated with this regimen.

OUTLINE: This is a pilot study.

• Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours 4 times daily on days -7 and -4, etoposide IV over 4 hours on day -3, and anti-thymocyte globulin IV over 6 hours on days -2 and -1.
• Donor umbilical cord blood transplantation (UCBT): Patients undergo donor UCBT on day 0. Beginning on day 7, patients receive sargramostim (GM-CSF) IV or subcutaneously once daily until blood counts recover.
• Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally twice daily beginning on day -2 and continuing until day 180 followed by a taper. Patients also receive oral prednisone twice daily on days 13-50 and then once daily on days 50-60, followed by a rapid taper.

After completion of study treatment, patients are followed periodically for approximately 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following advanced hematologic malignancies:

• Acute myeloid leukemia (AML) meeting the following criteria:

• Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

• High-risk cytogenetics (-7, -7q, -5, -5q, t[6,9], t[9,11], complex, Philadelphia chromosome positive [Ph+])
• AML evolved from prior myelodysplasia
• AML secondary to prior chemotherapy
• Failed to achieve remission
• In second or subsequent remission
• Marrow blasts ≤ 10% (may be achieved using chemotherapy)
• Myelodysplastic syndromes (MDS) with high-risk features

• International Prognostic Scoring System (IPSS) score intermediate -2 or high-risk
• Marrow blasts ≤ 20% (may be achieved using chemotherapy)
• Acute lymphoblastic leukemia meeting the following criteria:

• Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

• High-risk cytogenetics (Ph+, t[4,11], 11q23 abnormalities, and monosomy 7)
• Required > 1 induction course to achieve remission
• Failed to achieve remission
• In second or subsequent remission
• Marrow blasts ≤ 10% (may be achieved using chemotherapy)
• Chronic myelogenous leukemia meeting ≥ 1 of the following criteria:

• Accelerated phase
• Chronic phase refractory to imatinib mesylate
• Blastic phase

• Marrow blasts ≤ 10% (may be achieved using chemotherapy)
• Multiple myeloma meeting 1 of the following criteria:

• Stage II or III disease with > first relapse or refractory disease
• Newly diagnosed disease with chromosome 13 abnormalities
• Lymphoma meeting the following criteria:

• One of the following subtypes:

• Diffuse large cell lymphoma
• Mantle cell lymphoma
• Peripheral T-cell lymphoma
• T-natural killer (NK) cell lymphoma
• Hodgkin's lymphoma
• Disease failed to respond to primary therapy, progressed, or recurred after prior therapy

• Patients who have failed autologous stem cell transplantation are eligible provided it has been > 1 year since transplant
• No rapid progression of malignant disease
• Not eligible for autologous stem cell transplantation
• Available umbilical cord blood (1-3 units) donor matching at ≥ 4 of 6 HLA antigens (A, B, and DR)

• Patients with an HLA-identical or 1 antigen-mismatched related donor OR a potential HLA-matched unrelated donor matching at > 6/8 (A, B, C, DR) alleles are not eligible

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Creatinine < 2.0 mg/dL
• Creatinine clearance > 40 mL/min
• Bilirubin < 2.0 mg/dL
• AST and alkaline phosphatase < 3 times upper limit of normal
• Hepatitis C and active hepatitis B allowed if patient has ≤ grade 2 inflammation or fibrosis by liver biopsy
• Ejection fraction > 40% by echocardiogram or MUGA
• DLCO > 40% of predicted
• Not pregnant or nursing
• Negative pregnancy test
• No known HIV infection
• No active infection requiring ongoing antibiotic treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics