1. ¹Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
2. ²Europdonor Foundation, Leiden, The Netherlands
3. ³Department of Haematology, Erasmus MC/Daniel den Hoed, Rotterdam, The Netherlands

Correspondence: Dr MBA Heemskerk, Europdonor Foundation, Plesmanlaan 1 b, 2333 BZ Leiden, The Netherlands. E-mail: M.B.A.Heemskerk@lumc.nl

Received 11 August 2006; Revised 5 March 2007; Accepted 20 April 2007; Published online 28 May 2007.

Abstract

A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor–recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the -helices plus five or more differences in the -sheet (55) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a 55 mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03–0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.