Trial Information

T-Cell Depletion for Graft-Versus-Host Disease (GVHD) Prevention in High Risk Matched and Mismatched Allogeneic Bone Marrow Transplantation

OBJECTIVES: I. Determine the incidence and severity of graft vs host disease (GVHD)
following allogeneic bone marrow transplantation with marrow grafts modified by T cell
depletion with counterflow centrifugal elutriation and CD34+ cell selection in patients at
high risk for GVHD. II. Determine the incidence of graft failure following this treatment
regimen in this patient population. III. Determine the relapse rate and overall survival in
this patient population treated with this regimen.

OUTLINE: Patients with unrelated donors, mismatched related donors, or matched related
donors diagnosed with acute lymphocytic leukemia, chronic lymphocytic leukemia, myeloma, or
advanced acute myeloid leukemia (AML), receive cyclophosphamide IV over 60 minutes on days
-6 and -5 and fractionated total body irradiation (TBI) 3 times a day on days -3 through -1,
and twice on day 0. Patients receive graft vs host disease (GVHD) prophylaxis with
anti-thymocyte globulin (ATG) IV over 8 hours on days -2 and -1. Patients undergo allogeneic
bone marrow transplantation (ABMT) on day 0 with marrow grafts modified by T cell depletion
with counterflow centrifugal elutriation and CD34+ selection. Patients unable to receive TBI
due to matched or mismatched related donors, or age (56 to 60), or patients diagnosed with
AML-CR1, chronic myelogenous leukemia, myelodysplastic syndrome, or myeloproliferative
disorders with matched related donors, receive oral busulfan every 6 hours on days -7
through -4, cyclophosphamide IV over 60 minutes on days -3 and -2, and ATG IV over 8 hours
on days -2 and -1 for GVHD prophylaxis. Patients undergo T cell depleted ABMT on day 0. At
pretransplantation, patients with acute leukemia receive intrathecal (IT) methotrexate (MTX)
following lumbar puncture. At 48 hours following IT MTX, patients with CNS involvement
receive a second dose of IT MTX followed by oral leucovorin calcium every 6 hours for 4
doses. Patients with prior CNS involvement receive cranial radiotherapy for 2 weeks.
Following AMBT, patients undergo GVHD prophylaxis consisting of methylprednisolone IV every
12 hours on days 5-22, and then once daily on days 23-28 and cyclosporine IV or orally twice
daily beginning on day -1 and continuing until 7-9 months following ABMT. Patients are
followed every 3 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.