Originally published as JCO Early Release 10.1200/JCO.2007.11.1641 on December 17 2007

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valcárcel, D. Articles by Sierra, J. Search for Related Content PubMed PubMed Citation Articles by Valcárcel, D. Articles by Sierra, J. Social Bookmarking                            What's this?

Sustained Remissions of High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome After Reduced-Intensity Conditioning Allogeneic Hematopoietic Transplantation: Chronic Graft-Versus-Host Disease Is the Strongest Factor Improving Survival

David Valcárcel, Rodrigo Martino, Dolores Caballero, Jesus Martin, Christelle Ferra, Jose B. Nieto, Antonia Sampol, M. Teresa Bernal, Jose L. Piñana, Lourdes Vazquez, Jose M. Ribera, Joan Besalduch, Jose M. Moraleda, Dolores Carrera, M. Salut Brunet, Jose A. Perez-Simón, Jorge Sierra

From the Hospital de la Santa Creu i Sant Pau (Universitat Autonoma Barcelona), Barcelona; Hospital Clínico Universitario Salamanca, Salamanca; Hospital Germans Trias i Pujol, Badalona; Hospital Morales Meseguer, Murcia; Hospital Son Dureta, Palma de Mallorca, Mallorca; Hospital Central de Asturias, Ovieda, Spain

Corresponding author: David Valcárcel, MD, H. Santa Creu i Sant Pau, Sant Antoni Maia Claret 167, Barcelona, Spain 08025; e-mail: dvalcarcel{at}santpau.es

Purpose Reduced-intensity conditioning (RIC) for allogeneic stem-cell transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen–identical sibling by using a regimen that uses fludarabine and busulfan.

Patients and Methods Ninety-three patients with AML (n = 59) and MDS (n = 34) were included, and the median age was of 53 years. Follow-up for survivors was 43 months (range, 3 to 89 months). The conditioning regimen consisted of fludarabine (150 mg/m²) and oral busulfan (8 to 10 mg/kg). All except one patient received mobilized peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyslosporine and methotrexate or mycophenolate mofetil.

Results The 100-day, 1-year, and 4-year incidences of NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative incidences were 23% and 37%, respectively, and leukemia recurrence was the main cause of death. The 4-year disease-free survival (DFS) and overall survival (OS) rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic GVHD was 53% (45% extensive), and its development was the major factor associated with lower relapse incidence and improved DFS and OS.

Conclusion Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS.

published online ahead of print at www.jco.org on December 17, 2007.

Supported in part by the Instituto de Salud Carlos III (expedient Grant No. CM06/00,139, Ministerio de Sanidad to J.L.P., and Grants No. PI052312 and RD06/0020/0707 to J.S.); the Instituto de Recerca Hospital de la Santa Creu I Sant Pau (J.L.P.); and DURSI (Grant No. 2005SGR01075 to J.S.), Catalonia, Spain.

Both D.V. and R.M. contributed equally to this work and should be considered co–first authors.

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. P. Alessandrino, M. G. Della Porta, A. Bacigalupo, M. T. Van Lint, M. Falda, F. Onida, M. Bernardi, A. P. Iori, A. Rambaldi, R. Cerretti, et al. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) Blood, August 1, 2008; 112(3): 895 - 902. [Abstract] [Full Text] [PDF]