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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-11-3503. This Article Full Text (PDF) All Versions of this Article: 2002-11-3503v1 102/3/1108    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Perez-Simon, J. A Articles by San Miguel, J. F Search for Related Content PubMed PubMed Citation Articles by Perez-Simon, J. A Articles by San Miguel, J. F Social Bookmarking                   What's this? Submitted November 27, 2002 Accepted March 10, 2003 Impact of CD34+ cell dose on the outcome of patients undergoing reduced intensity conditioning allogeneic peripheral blood stem cell transplantation Jose A Perez-Simon*, Maria Diez-Campelo, Rodrigo Martino, Anna Sureda, Dolores Caballero, Consuelo Canizo, Salut Brunet, Albert Altes, Lourdes Vazquez, Jordi Sierra, and Jesus F San Miguel Department of Hematology, Hospital Clinico Universitario de Salamanca, Salamanca, Spain Department of Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain * Corresponding author; email: pesimo{at}usal.es. Information regarding the optimal dose of hematopoietic progenitor cells for infusion in allogeneic transplantation remains controversial. The present study analyzes the impact of CD34+ cell dose infused on the outcome of 86 patients receiving a reduced intensity conditioning (RIC) allogeneic PBSC transplant. This RIC was based on fludarabine 150 mg/m2 intravenously (IV) followed by melphalan 140 mg/m2 IV or busulphan 10 mg/kg for patients diagnosed with lymphoid or myeloid malignancies, respectively. A median of 5.68 x 106 CD34+ cells/kg and 2.86 x 108 CD3+ cells/kg were infused. While neither the number of CD3+ cells nor the CD34+ cell dose infused influenced the speed of hematopoietic recovery, 100% of patients receiving > percentile 75 (p75) of CD34+ cells reached complete chimerism in T-lymphocytes by days 21 to 28 as compared to 44% among those receiving p75 (p=0.046). Overall, 30.3% patients developed grades 2-4 aGVHD. Among 83 evaluable patients, 55.8% developed cGVHD. Neither CD34+ nor CD3+ cell dose affected the incidence of aGVHD. By contrast, the dose of CD34+ cells infused influenced the development of cGVHD, with a cumulative incidence of extensive cGVHD of 74% vs 47% (p=0.02) among patients receiving >p75 vs p75 CD34+ cells. After a median follow up of 385 days 25 patients died, 17 (19.8%) of them due to transplant related mortality (TRM). Projected OS and EFS at 43 months were 60 and 46 % respectively. Neither the dose of CD34+ cells nor the CD3+ cells infused significantly influenced OS and EFS, although among patients categorized as high risk group according to disease status at transplant 36% of those receiving p75 CD34+ cells relapsed or progressed as compared to only 9% among those receiving >p75 CD34+ cells (p=0.07). Even more, among patients receiving p75 CD34+ cells, 36% of high risk patients relapsed as compared to only 10% of low and intermediate risk patients (p=0.004) while relapse rate was not significantly different between high risk and low-intermediate risk patients when we infused > p75 CD34+ cells, thus indicating that infusing high doses of CD34+ cells among high risk patients ameliorates the negative effect of advanced disease status at transplant. In addition, chronic GVHD was associated with a better EFS (63% vs 16% at 43 months for patients with and without cGVHD, respectively; p<0.0001) and better OS (78% vs 28% for patients with and without cGHVD, respectively; p<0.001). The number of CD34+ cells infused should be cautiously tailored in order to prevent extensive cGVHD among patients categorized as low risk according to disease status pretransplant, while high risk patients, in whom GVL may determine disease outcome, should receive high doses of CD34+ cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. Pulsipher, P. Chitphakdithai, B. R. Logan, S. F. Leitman, P. Anderlini, J. P. Klein, M. M. Horowitz, J. P. Miller, R. J. King, and D. L. 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