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Originally published as JCO Early Release 10.1200/JCO.2005.03.1765 on December 12 2005

Journal of Clinical Oncology, Vol 24, No 3 (January 20), 2006: pp. 444-453
© 2006 American Society of Clinical Oncology.

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Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors

Ute Hegenbart, Dietger Niederwieser, Brenda M. Sandmaier, Michael B. Maris, Judith A. Shizuru, Hildegard Greinix, Catherine Cordonnier, Bernard Rio, Alois Gratwohl, Thoralf Lange, Haifa Al-Ali, Barry Storer, David Maloney, Peter McSweeney, Thomas Chauncey, Ed Agura, Benedetto Bruno, Richard T. Maziarz, Finn Petersen, Rainer Storb

From the University of Leipzig, Leipzig, Germany; Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA; Stanford University, Palo Alto, CA; Bone Marrow Transplant Unit, Medical University of Vienna, Austria; Hopital Henri Mondor, Creteil, Hotel Dieu, Paris, France; University Hospital, Basel, Switzerland; University of Colorado, Denver, CO; Seattle Veterans Administration Medical Center, Seattle, WA; Baylor University, Dallas, TX; University of Torimo, Torimo, Italy; Oregon Health & Science University, Portland, OR; and University of Utah, Salt Lake City, UT

Address reprint requests to Dietger Niederwieser, MD, Division of Hematology and Oncology, University of Leipzig, Johannissallee 32A, D-4103 Leipzig, Germany; e-mail: dietger{at}medizin.uni-leipzig.de

Purpose: The use of low-dose, irradiation-based preparative regimens have allowed the extension of allografting to older and medically infirm patients. The study reported here assessed outcomes for patients with acute myeloid leukemia (AML) in different stages of their disease, who were not considered candidates for conventional hematopoietic cell transplantation (HCT) because of age and/or other known risk factors and were given minimal conditioning followed by HCT from related or unrelated donors.

Patients and Methods: The present study included 122 patients with AML, who were conditioned with 2 Gy total-body irradiation (TBI) on day 0 with or without preceding fludarabine (30 mg/m2/d from days –4 to –2), and given postgrafting cyclosporine at 6.25 mg/kg twice daily from day –3 and mycophenolate mofetil at 15 mg/kg twice daily from day 0.

Results: Durable engraftment was observed in 95% of the patients. Cumulative incidences of acute graft-versus-host disease grades 2 to 4 at 6 months were 35% after related and 42% after unrelated HCT, respectively. With a median follow-up of 44 months (range, 26 to 79 months), 51 patients were alive, of whom 48 were in complete remission (CR). Cumulative nonrelapse mortalities were 10% and 22%, and cumulative mortalities from disease progression were 47% and 33% at 2 years for related and unrelated recipients, respectively. Overall, 2-year survival was 48%, and disease-free survival was 44%. Patients receiving transplantation in CR1 had 2-year overall survivals of 44% after related and 63% after unrelated HCT, respectively.

Conclusion: We conclude that HCT from related and unrelated donors after low-dose TBI is a promising treatment for elderly patients with AML.

Supported by grants CA 18029, CA 15704, CA 78902, and HL 36444 from the National Institutes of Health, Bethesda, MD and by the EU grant European Leukemia Net and the Swiss National Research Foundation.

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




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