SEARCH:   Advanced

Blood, 15 May 2005, Vol. 105, No. 10, pp. 4147-4148. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Spyridonidis, A. Articles by Finke, J. Search for Related Content PubMed PubMed Citation Articles by Spyridonidis, A. Articles by Finke, J. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE To the editor: Hematopoietic cell transplantation from unrelated donors as an effective therapy for older patients ( 60 years) with active myeloid malignancies In recent years, several groups including ours have reported on the feasibility of allografting debilitated or advanced-aged patients using reduced intensity conditioning (RIC) regimens.1-6 However, because of the heterogeneity in the study populations, information on the efficacy of RIC transplantations from unrelated donors to control high-risk/active elderly acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) has remained limited. We focused on a homogenous group of 34 consecutive older patients ( 60 years) with high-risk, active AML/MDS (28 patients with AML; 6 with MDS) allografted from unrelated donors after conditioning with a uniform RIC regimen and receiving a uniform graft-versus-host disease (GvHD) prophylaxis (cyclosporine, mycophenolate mofetil, rabbit anti–T-lymphocyte globulin [ATG] [Fresenius, Graefelfing, Germany] 20 mg/kg per day at day -1 to day -2). The preparative regimen consisted of fludarabine (30 mg/m2 per day at day –9 to day –5) combined with 2 alkylating agents given in moderate doses (BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] 150 mg/m2 per day at day –7 to day –6; melphalan 110 mg/m2 at day –4) (FBM). Detailed information of patient characteristics and transplantation outcomes are given in Tables 1 and 2. View this table: [in this window] [in a new window]   Table 1.. Patient and graft characteristics   View this table: [in this window] [in a new window]   Table 2.. Transplantation outcomes   The high rates of sustained engraftment (100%), early full donor chimerism (97%), and blast clearance (100% patients achieved CR) obtained underscore the myeloablative character and the high antileukemic potential of the FBM/ATG/peripheral blood–hematopoietic cell transplantation (PB-HCT) strategy. Of note, at HCT 91% of patients had active disease and 38% of patients had uncontrolled AML after a median of 2 intensive chemotherapies. On the other hand, the FBM regimen was tolerated fairly well and the procedure is relatively safe since nonrelapse mortality (NRM) was low (6 deaths; 2-year cumulative risk, 19.6% [95% CI, 9.5%-40.4%]) and mainly due to fungal infections (3 early deaths), and therefore principally related to the pretransplantation state of the patient (long neutropenia, history of aspergillosis). To avoid this complication, transplantation early during the disease course would be an option. View larger version (7K): [in this window] [in a new window]   Figure 1..   The incidence of acute and chronic GvHD was comparable with that reported in younger patients. On median day +170, 9 patients relapsed (2-year cumulative relapse risk, 27.3% [95% CI, 15%-49.7%]). Of 7 relapsed patients, 3 responded to donor lymphocyte infusions (DLIs) and 2 patients overall were successfully salvaged (1 with DLI, 1 with second HCT). After a median follow-up of 913 days (range, 55-1591 days), 22 patients (65%) are alive with all but 1 in complete remission (CR). Most of the survivors report feeling well (median Karnofsky performance score [KPS], 100%; 70-100), with only 2 patients requiring chronic immunosuppression. The actuarial 2-year overall survival (OS) and event-free survival (EFS) probability were 62.7% (95% CI, 44.9%-80.4%) and 53.1% (95% CI, 34.8%-71.4%), respectively (Figure 1). Interestingly, higher numbers of CD34+ cells in the PB graft were associated with improved outcome (P = .044). This correlation could not be explained by a higher incidence of chronic GvHD with increasing numbers of CD34+ PB cells, as suggested by others.7 Since age affects CD34+ cell yield during apheresis, it seems reasonable to consider lower age as a selection criterion when choosing a donor. Allogeneic PB-HCT from unrelated donors using the FBM/ATG protocol is an effective treatment for patients 60 years or older with high-risk myeloid malignancies. The sustained remissions observed in 7 of 11 previously untreated sAML (AML secondary to MDS) or MDS patients suggest that at least for candidates with a slow increase of blasts over time, transplantation may be used as a front-line therapy. Alexandros Spyridonidis, Hartmut Bertz, Gabriele Ihorst, Carsten Grüllich, and Jürgen Finke Correspondence: Jürgen Finke, Freiburg University Medical Center, Hugstetterstrasse 55, 79106 Freiburg, Germany; e-mail: finke{at}mm11.ukl.unifreiburg.de References Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol. 2003;21: 1480-1484.[Abstract/Free Full Text] Wong R, Giralt SA, Martin T, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood. 2003;102: 3052-3059.[Abstract/Free Full Text] Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102: 2021-2030.[Abstract/Free Full Text] Ho AY, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic haematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukaemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood. 2004;104: 1616-1623.[Abstract/Free Full Text] Chakraverty R, Peggs K, Chopra R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002;99: 1071-1078.[Abstract/Free Full Text] de Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104: 857-864.[Abstract/Free Full Text] Perez-Simon JA, Diez-Campelo M, Martino R, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood. 2003;102: 1108-1113.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Schetelig, M. Bornhauser, C. Schmid, B. Hertenstein, R. Schwerdtfeger, H. Martin, M. Stelljes, U. Hegenbart, K. Schafer-Eckart, M. Fussel, et al. Matched Unrelated or Matched Sibling Donors Result in Comparable Survival After Allogeneic Stem-Cell Transplantation in Elderly Patients With Acute Myeloid Leukemia: A Report From the Cooperative German Transplant Study Group J. Clin. Oncol., November 10, 2008; 26(32): 5183 - 5191. [Abstract] [Full Text] [PDF] B. Hackanson, H. Becker, T. Berg, M. Binder, C. Dierks, J. Duque-Afonso, M. D. Lairmore, H. S. Schafer, M. Schnitzler, R. Zeiser, et al. XXIII International Association for Comparative Research on Leukemia and Related Diseases Symposium: from Molecular Pathogenesis to Targeted Therapy in Leukemia and Solid Tumors Cancer Res., July 15, 2008; 68(14): 5512 - 5518. [Full Text] [PDF] R. Marks, K. Potthoff, J. Hahn, G. Ihorst, H. Bertz, A. Spyridonidis, E. Holler, and J. M. Finke Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies Blood, July 15, 2008; 112(2): 415 - 425. [Abstract] [Full Text] [PDF] Z. Xing, M. A. Ryan, D. Daria, K. J. Nattamai, G. Van Zant, L. Wang, Y. Zheng, and H. Geiger Increased hematopoietic stem cell mobilization in aged mice Blood, October 1, 2006; 108(7): 2190 - 2197. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Spyridonidis, A. Articles by Finke, J. Search for Related Content PubMed PubMed Citation Articles by Spyridonidis, A. Articles by Finke, J. Social Bookmarking                   What's this?

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020