Trial Information

ALLOGENEIC AND SYNGENEIC MARROW TRANSPLANTATION IN PATIENTS WITH ACUTE NON-LYMPHOCYTIC LEUKEMIA

OBJECTIVES: I. Determine overall and leukemia-free survival of patients with acute
nonlymphocytic leukemia or myelodysplastic syndrome treated with busulfan and
cyclophosphamide (low-risk patients) or cytarabine, busulfan, and cyclophosphamide
(high-risk patients) followed by allogeneic or syngeneic bone marrow transplantation. II.
Compare the therapeutic effects of these cytoreduction regimens with those reported in the
literature for similar patients who undergo syngeneic or allogeneic marrow transplantation
following cytoreduction that includes total-body irradiation. III. Determine the early and
late toxic effects produced by these chemotherapy regimens in this patient population.

OUTLINE: Low-risk patients (those in first complete remission (CR) who achieved CR with 1
course of chemotherapy) are treated on Regimen A. High-risk patients (those in second or
subsequent CR who required more than 1 course of chemotherapy to achieve first CR or those
with myelodysplastic syndrome) are treated on Regimen B. All patients undergo diagnostic
lumbar puncture prior to beginning therapy and fluid is examined for CNS disease. Patients
receive methotrexate IT along with the tap. Prior to initiation of chemotherapy, patients
with CNS disease present on diagnostic lumbar puncture receive methotrexate IT every 2-3
days until lumbar puncture shows no leukemia cells and then 1 additional dose. Cytoreductive
chemotherapy begins 3 days after the last dose of methotrexate. Regimen A: Patients receive
oral busulfan every 6 hours on days -7 to -4 for a total of 16 doses and cyclophosphamide IV
over 2 hours on days -3 and -2. Allogeneic bone marrow is infused on day 0. Regimen B:
Patients receive oral busulfan every 6 hours on days -9 to -6 for a total of 16 doses.
Patients receive cytarabine IV over 1 hour every 12 hours on days -5 and -4 and
cyclophosphamide IV over 2 hours on days -3 and -2. Allogeneic bone marrow is infused on day
0. Graft versus host disease prophylaxis: Patients receive cyclosporine IV continuously on
days -1 to 28 followed by a taper of oral cyclosporine until day 180. Patients receive
methotrexate IV on days 1, 3, 6, and 11. CNS disease prophylaxis: Patients receive 5 more
doses of methotrexate IT weekly beginning between days 50 and 70. In addition, patients with
history of CNS disease receive 1 dose of methotrexate IT monthly for 1 year. Patients are
followed frequently during the first 100 days, at 6 months, 1 year, and then annually
thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2.7 years.