Originally published as JCO Early Release 10.1200/JCO.2006.05.5855 on July 31 2006

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Results of Genoidentical Hemopoietic Stem Cell Transplantation With Reduced Intensity Conditioning for Acute Myelocytic Leukemia: Higher Doses of Stem Cells Infused Benefit Patients Receiving Transplants in Second Remission or Beyond—The Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation

Norbert-Claude Gorin, Myriam Labopin, Jean-Michel Boiron, Niklas Theorin, Tim Littlewood, Shimon Slavin, Hildegard Greinix, Jean Yves Cahn, E. Paolo Alessandrino, Alessandro Rambaldi, Arnon Nagler, Emmanuelle Polge, Vanderson Rocha

From the Department of Haematology and Cell Therapy; the European Group for Blood and Marrow Transplantation Acute Leukemia Working Party, Hopital Saint-Antoine Asistance Publique Hopitaux de Paris and Université Paris 6, Pierre et Marie Curie; Department of Hematology, Hopital Saint-Louis Asistance Publique Hopitaux de Paris and Uniersité Paris, Paris; Centre Hospitalo Universitaire Bordeaux, Hôpital Haut-leveque, Pessac; Hopital A. Michallon, Department of Oncology-Hematology and Université Joseph Fourier, Grenoble, France; University Hospital, Department of Hematology, Linköping, Sweden; The Oxford Radcliffe Hospital, Clinical Haematology, Oxford, United Kingdom; Hadassah University Hospital, Department of Bone Marrow Transplantation, Jerusalem; Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Medizinische Universitaet Wien, Klinik fuer Innere Medizin I, Vienna, Austria; Policlinico San Matteo, Department of Hematology, Bone Marrow Transplantation unit, Institute for Research Against Cancers, Pavia; and the Ospedale Bergamo, Divisione di Ematologia, Bergamo, Italy

Address reprint requests to Norbert-Claude Gorin, MD, PhD, Hopital Saint-Antoine, 184 rue du faubourg Saint-Antoine, Paris 75571 France; e-mail: norbert-claude.gorin{at}sat.aphp.fr

PURPOSE: Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known.

PATIENTS AND METHODS: From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CR1), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in 91% of patients and low-dose (< 4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1x 10⁸/kg and 5.8x 10⁶/kg, respectively.

RESULTS: Overall, 2-year leukemia-free survival (LFS) was 41% ± 4% and it was 46% ± 5% for patients receiving a higher cell dose (> 9.1x 10⁸/kg) and 37% ± 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 ± 8 versus 20 ± 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes.

CONCLUSION: Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than in CR1.

published online ahead of print at www.jco.org on July 31, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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