ORIGINAL ARTICLE Predictive impact of allele-matching and EBMT risk score for outcome after T-cell depleted unrelated donor transplantation in poor-risk acute leukemia and myelodysplasia T Lodewyck 1 , M Oudshoorn 2 , B van der Holt 3 , E Petersen 4 , E Spierings 5 , PA von dem Borne 6 , A Schattenberg 7 , W Allebes 8 , M Groenendijk-Sijnke 9 , L Duinhouwer 1 , R Willemze 6 , B Lowenberg 1 , LF Verdonck 10 , E Meijer 1 and JJ Cornelissen 1 1 Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands; 2 Europdonor Foundation and Department of Immunohematology & Blood Transfusion Service, Leiden University Medical Center, Leiden, The Netherlands; 3 Trials & StatisticsFHOVON Data Center, Erasmus University Medical Center/Daniel den Hoed, Rotterdam, The Netherlands; 4 Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; 5 Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; 6 Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; 7 Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 8 Laboratory for Medical Immunology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 9 HOVON Data Center, Erasmus University Medical Center, Rotterdam, The Netherlands and 10 Department of Internal Medicine, Isala Clinics, Zwolle, The Netherlands Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (p7/8) pairs (P ¼ 0.02). Patients with EBMT risk scores of 1–2, 3, 4 and 5–7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (Po0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1–2). Five- year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with p7/8 donors. These data underscore the impor- tance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT. Leukemia (2011) 25, 1548–1554; doi:10.1038/leu.2011.123; published online 24 May 2011 Keywords: acute leukemia; allele-matching; unrelated donor transplantation Introduction Allogeneic hematopoietic stem cell transplantation (alloSCT) is an established treatment modality to consolidate remission in patients with acute leukemia. 1–4 However, non-relapse mortal- ity (NRM) may partially offset the favorable immunotherapeutic effect of alloSCT and, as a result, only well-selected patients may benefit. Recent meta-analyses of prospective sibling donor versus no-donor studies have shown a survival advantage for donor-availability in acute myeloid leukemia (AML) patients in first complete remission (CR1), who lack favorable cytogenetics and acute lymphoblastic leukemia (ALL) patients in CR1 with a standard or high-risk profile. 5–9 In addition, alloSCT is generally considered the treatment of choice in acute leukemia patients in second or subsequent CR. Whereas alloSCT is preferably performed with sibling donors, matched unrelated donors (URDs) are increasingly applied. 10 AlloSCT using an URD may be associated with a somewhat higher risk of NRM as compared with alloSCT from HLA-identical sibling donors, although results using molecularly matched donors may approximate those using sibling donors. 11–17 Apart from HLA- match, NRM after alloSCT depends on many parameters, including age, cytomegalovirus (CMV) serostatus, disease stage, donor-recipient gender combination, performance status and comorbidity of the patient. Two different risk scores (the European Group of Blood and Marrow Transplantation (EBMT) risk score and the hematopoietic cell transplantation specific comorbidity index (HCT-CI)) have been developed incorporat- ing selected parameters, and have been demonstrated to predict NRM after alloSCT. 18–23 The EBMT risk score is based on 5 parameters, including patient age, disease stage, time between diagnosis and transplantation, type of donor and gender combination. The score was initially designed to predict outcome after alloSCT for chronic myeloid leukemia (CML) and has recently been validated in acute leukemia and myelodysplastic syndrome (MDS). 18,19 The score accurately predicts for overall survival (OS) and NRM, including a NRM of less than 20% in patients with a score of 0, a NRM of 20–30% for a score of 1–2, a NRM of 30–40% for a score of 3 and a NRM 440% in patients with 4 or more points. We set out to evaluate the relative prognostic value of high-resolution HLA-matching status and EBMT risk score on OS and NRM in a cohort of patients with high-risk acute leukemia or MDS receiving an URD alloSCT. Patients and methods Patients A total of 327 patients who received hematopoietic stem cell grafts from volunteer URDs were included in this analysis. Received 2 November 2010; revised 24 January 2011; accepted 23 February 2011; published online 24 May 2011 Correspondence: Professor JJ Cornelissen, Department of Hematology, Erasmus University Medical Center, Daniel den Hoed Cancer Cliniques (DDHK), Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. E-mail: j.cornelissen@erasmusmc.nl Leukemia (2011) 25, 1548–1554 & 2011 Macmillan Publishers Limited All rights reserved 0887-6924/11 www.nature.com/leu