Phase I Study of Sequential Cord Blood Transplants

Eligible patients will receive conditioning therapy with fludarabine 30 mg/m2/day x 6 days, melphalan 100 mg/m2/day x 1 day, rabbit antithymocyte globulin 1.5 mg/kg/day x 4 days. GVHD prophylaxis will consist of cyclosporine starting on day -1 and mycophenolate mofetil starting on day 0. Sequential cord blood units will be infused on Day 0.

Inclusion criteria

• Disease Status: NHL, HD, or MM refractory to chemotherapy or relapsed; CLL Rai Stage III/IV, or lymphocyte doubling time of 6 months, or Stage I/II resistant to 2 chemotherapy regimens; AML or ALL in second or subsequent remission or in first remission with adverse cytogenetics or antecedent hematologic disorder
• Estimated disease-free survival of less than one year
• ECOG performance status of 0, 1, 2
• Lack of 6/6 or 5/6 HLA matched related or 6/6 matched unrelated donor, or a donor is not available within the time frame necessary to perform a potentially curative stem cell transplant
• 4/6 or greater HLA A, B, CRB1 cord blood units with a combined nucleated cell dose from of > 3.7 x 10(7) NC/kg

Exclusion criteria

• Cardiac disease: symptomatic congestive hearth failure or RVG or echocardiogram determined left ventricular ejection fraction of < 45%, active angina pectoris, or uncontrolled hypertension
• Pulmonary Disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO of < 50%
• Renal disease: serum creatinine > 2.0 mg/dl
• Hepatic disease: serum bilirubin > 2.0 mg/dl (except in the case of Gilbert's syndrome), SGPT or SGOT > 3 x normal
• Neurologic disease: symptomatic leukoencephalopathy, active DNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
• HIV antibody or Hepatitis B surface antigen positivity
• Uncontrolled infection
• Pregnancy or breast-feeding mother