TRANSPLANTATION FOR NHL--COMPARISON OF PSCT AND ABMT

The objective of this clinical proposal is to identify the optimal source
of hematopoietic stem cell rescue following high-dose chemotherapy given
for non-Hodgkin's lymphoma (NHL). In a preliminary non-randomized
clinical study, patients with intermediate grade NHL who received an
autologous bone marrow transplant (ABNT) (N=105) had a three year event-
free survival (EFS) of 24%. This compared to a three year EFS of 38% in
patients with intrinsic bone marrow abnormalities who underwent high-dose
therapy with peripheral stem cell transplantation (PSCT) (N=53) (1). The
clinical trial in this proposal will randomize patients with intermediate
grade or immunoblastic NHL to receive high-dose chemotherapy with
hematopoietic reconstitution with either ABMT or PSCT. All patients will
have histologically negative bone marrow and will be stratified before
randomization by other recognized prognostic factors. The two companion
laboratory studies will evaluate possible mechanisms to explain
differences in outcome observed between the patients receiving an
autologous bone marrow or a peripheral stem cell transplant. One study
will evaluate the presence of occult tumor cells as minimal residual
disease in the graft by in-vitro tumor culture assays and molecular
biologic techniques. The other laboratory study will evaluate phenotype
of cells within the hematopoietic graft given back to the patient, as well
as the re-appearance of immuno-competent cells in the patients post-
transplant, including natural killer cell and leukocyte activated killer
cell activity, cell phenotype by flow cytometric analysis, as well as
functional analysis. The findings in the laboratory studies will be
correlated to the survival and event-free survival in the patients
receiving high-dose chemotherapy with ABMT or PSCT.