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Engraftment of allogeneic hematopoietic progenitor cells with purine
analog-containing chemotherapy: harnessing graft-versus-leukemia without
myeloablative therapy
S Giralt, E Estey, M Albitar, K van Besien, G Rondon, P Anderlini, S O'Brien, I Khouri, J Gajewski, R Mehra, D Claxton, B Andersson, M Beran, D Przepiorka, C Koller, S Kornblau, M Korbling, M Keating, H Kantarjian and R Champlin
Department of Hematology, The University of Texas M.D. Anderson Cancer
Center, Houston 77030, USA.
The immune-mediated graft-versus-leukemia effect is important to prevent
relapse after allogeneic progenitor cell transplantation. This process
requires engraftment of donor immuno-competent cells. The objective of this
study was to assess the feasibility of achieving engraftment of allogeneic
peripheral blood or bone marrow progenitor cell after purine analog
containing nonmyeloablative chemotherapy. Patients with advanced leukemia
or myelodysplastic syndromes (MDS) who were not candidates for a
conventional myeloablative therapy because of older age or organ
dysfunction were eligible. All patients had an HLA- identical or
one-antigen-mismatched related donor. Fifteen patients were treated (13
with acute myeloid leukemia and 2 with MDS). The median age was 59 years
(range, 27 to 71 years). Twelve patients were either refractory to therapy
or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d
for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d
for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients
received 2-chloro- deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at
g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood
stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host
disease (GVHD) prophylaxis consisted of cyclosporine and methyl-
prednisolone. Treatment was generally well tolerated, with only 1 death
from multiorgan failure before receiving stem cells. Thirteen patients
achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10
days postinfusion (range, 8 to 17 days). Ten patients achieved platelet
counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion
(range, 7 to 78 days). Eight patients achieved complete remissions (bone
marrow blasts were < 5% with neutrophil recovery and platelet
transfusion independence) that lasted a median of 60 days
posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2
occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8
patients achieving remission showed > or = 90% donor cells between 14
and 30 days postinfusion, and 3 of 4 patients remaining in remission
between 60 and 90 days continued to have > or = 80% donor cells. We
conclude that purine analog-containing nonmyeloablative regimens allow
engraftment of HLA-compatible hematopoietic progenitor cells. This approach
permits us to explore the graft-versus-leukemia effect without the toxicity
of myeloablative therapy and warrants further study in patients with
leukemia who are ineligible for conventional transplantation with
myeloablative regimens either because of age or concurrent medical
conditions.
Volume 89,
Issue 12,
pp. 4531-4536,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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