Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy

Harnessing graft-versus-leukemia without myeloablative therapy

Sergio Giralt, Elihu Estey, Maher Albitar, Koen Van Besien, Gabriela Rondón, Paolo Anderlini, Susan O'Brien, Issa Khouri, James Gajewski, Rakesh Mehra, David Claxton, Borje Andersson, Miloslav Beran, Donna Przepiorka, Charles Koller, Steve Kornblau, Martin Körbling, Michael Keating, Hagop Kantarjian, Richard Champlin

Research output: Contribution to journalArticle

1020 Citations (Scopus)

Abstract

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-deoxy-adenosine 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 109/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 109/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were

Original languageEnglish (US)
Pages (from-to)4531-4536
Number of pages6
JournalBlood
Volume89
Issue number12
StatePublished - Jun 15 1997
Externally publishedYes

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Chemotherapy
Hematopoietic Stem Cells
Grafts
Bone
Leukemia
Stem cells
Transplants
Drug Therapy
Blood
Idarubicin
Melphalan
Cytarabine
Platelets
Prednisolone
Stem Cells
Refractory materials
Adenosine
Cyclosporine
Therapeutics
Myelodysplastic Syndromes

ASJC Scopus subject areas

  • Hematology

Cite this

Giralt, S., Estey, E., Albitar, M., Van Besien, K., Rondón, G., Anderlini, P., ... Champlin, R. (1997). Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy. Blood, 89(12), 4531-4536.

Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy : Harnessing graft-versus-leukemia without myeloablative therapy. / Giralt, Sergio; Estey, Elihu; Albitar, Maher; Van Besien, Koen; Rondón, Gabriela; Anderlini, Paolo; O'Brien, Susan; Khouri, Issa; Gajewski, James; Mehra, Rakesh; Claxton, David; Andersson, Borje; Beran, Miloslav; Przepiorka, Donna; Koller, Charles; Kornblau, Steve; Körbling, Martin; Keating, Michael; Kantarjian, Hagop; Champlin, Richard.

In: Blood, Vol. 89, No. 12, 15.06.1997, p. 4531-4536.

Research output: Contribution to journalArticle

Giralt, S, Estey, E, Albitar, M, Van Besien, K, Rondón, G, Anderlini, P, O'Brien, S, Khouri, I, Gajewski, J, Mehra, R, Claxton, D, Andersson, B, Beran, M, Przepiorka, D, Koller, C, Kornblau, S, Körbling, M, Keating, M, Kantarjian, H & Champlin, R 1997, 'Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy', Blood, vol. 89, no. 12, pp. 4531-4536.
Giralt, Sergio ; Estey, Elihu ; Albitar, Maher ; Van Besien, Koen ; Rondón, Gabriela ; Anderlini, Paolo ; O'Brien, Susan ; Khouri, Issa ; Gajewski, James ; Mehra, Rakesh ; Claxton, David ; Andersson, Borje ; Beran, Miloslav ; Przepiorka, Donna ; Koller, Charles ; Kornblau, Steve ; Körbling, Martin ; Keating, Michael ; Kantarjian, Hagop ; Champlin, Richard. / Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy : Harnessing graft-versus-leukemia without myeloablative therapy. In: Blood. 1997 ; Vol. 89, No. 12. pp. 4531-4536.
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abstract = "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-deoxy-adenosine 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 109/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 109/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were",
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