T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies

OBJECTIVES:

Primary

- Determine engraftment in patients with hematologic malignancies treated with
T-cell-depleted allogeneic stem cell transplantation after immunoablative induction
chemotherapy and reduced-intensity transplantation conditioning.

Secondary

- Determine the incidence of acute graft-versus-host disease (GVHD), and nonrelapse
mortality (within 100 days after transplantation) in these patients.

- Correlate levels of host immunosuppression before transplantation conditioning, as
evaluated by peripheral blood CD4 counts, with graft rejection/failure within 100 days
after transplantation and the level of donor hematopoietic chimerism 28 days after
transplantation in these patients.

- Correlate donor-versus-recipient natural killer cell alloreactivity with graft
rejection/failure, acute GVHD, and relapse of malignant disease in patients treated
with this regimen.

- Determine the development of allospecific cytotoxic T-lymphocytes after transplantation
in patients with myeloid or lymphoid leukemia.

- Correlate serum interleukin-7 and interleukin-15 levels with in vivo changes in host
lymphocyte subpopulations in these patients during sequential immunoablative
chemotherapy, before allogeneic stem cell transplantation, and during immune
reconstitution after transplantation.

OUTLINE: This is a pilot study.

- Induction chemotherapy: Patients receive 1 of 2 induction chemotherapy regimens
according to diagnosis. Patients with partial response or better after prior therapy
(i.e., already adequately immune depleted) proceed directly to the transplantation
preparative regimen.

- Regimen A (Hodgkin's lymphoma, non-Hodgkin's lymphoma [except lymphoblastic
lymphoma], chronic lymphocytic leukemia, prolymphocytic leukemia, or multiple
myeloma): Patients receive rituximab IV (if they have CD20+ B-cell malignancies)
on day 1; fludarabine IV over 30 minutes on days 1-4; etoposide, doxorubicin, and
vincristine IV continuously on days 1-4; cyclophosphamide IV over 30 minutes on
day 5; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously (SC)
beginning on day 6 and continuing until blood counts recover.

- Regimen B (lymphoblastic lymphoma, acute myeloid leukemia, acute lymphoblastic
leukemia, refractory anemia with excess blasts, myeloproliferative disorders,
chronic myelomonocytic leukemia, or chronic myelogenous leukemia): Patients
receive G-CSF SC beginning 24 hours before initiating induction chemotherapy and
continuing until blood counts recover. Patients also receive fludarabine IV over
30 minutes and cytarabine IV over 4 hours on days 1-5.

For both regimens, treatment repeats every 21 days for 1-2 courses. Patients who achieve
remission or who have responsive or stable disease after induction chemotherapy then proceed
to transplantation preparative regimen chemotherapy.

- Transplantation preparative regimen chemotherapy: Patients receive fludarabine IV over
30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
hours twice daily beginning on day -1 and continuing IV or orally until day 100.
Patients with no acute GVHD at day 100 taper cyclosporine over 12 weeks.

- Allogeneic stem cell transplantation (SCT): Patients undergo T-cell-depleted allogeneic
peripheral blood SCT on day 0. Patients receive G-CSF SC beginning on day 0 and
continuing until blood counts recover.

- Donor lymphocyte infusion (DLI): Patients with persistent or progressive malignant
disease after transplantation or mixed chimerism that does not improve after tapering
or discontinuing immunosuppression therapy may receive DLI. DLI may be administered
alone or in combination with chemotherapy. DLI repeats every 4 weeks until adequate
donor chimerism is achieved or until GVHD develops.

Patients are followed at 28 and 100 days and then at 6, 9, 12, 18, and 24 months.

PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study within 2 years.