1. ¹Division of Immunology and Allergology, University Hospital, Geneva, Switzerland
2. ²Diagnostic and Therapeutic Hematology, Kantonsspital Basel, Switzerland
3. ³Leiden University Medical Centre, Leiden, The Netherlands
4. ⁴Bone Marrow Transplantation, University Hospital Hamburg, Germany
5. ⁵Division of Hematology, University Hospital, Geneva, Switzerland
6. ⁶Section of Hematology, Medical Department, Rikshospitalet University Hospital, Oslo, Norway
7. ⁷Department of Hematology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands
8. ⁸Europdonor Foundation and Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands
9. ⁹Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
10. ¹⁰Division of Hematology and Oncology, University of Leipzig, Leipzig, Germany

Correspondence: Dr J-M Tiercy, Transplantation Immunology Unit/LNRH, Division of Immunology & Allergology, University Hospital of Geneva, 24 rue Micheli-du-Crest, CH-1211 Genève 14, Switzerland. E-mail: Jean-Marie.Tiercy@hcuge.ch

Received 10 December 2003; Accepted 20 March 2004; Published online 7 June 2004.

Abstract

HLA-incompatibility is a major factor associated with outcome of allogeneic stem cell transplantation, but little is known on the impact of isolated HLA-C mismatches. We analyzed the outcome of 114 CML patients transplanted with marrow from unrelated donors of whom 24 were mismatched for HLA-C only (9/10 match). Univariate estimates of 5-year survival (SRV) (median follow-up: 47 months) in the HLA-matched group were 6812 vs 4220% (P=0.03) for the patients mismatched for HLA-C only and 3333% in the mismatched group (non-HLA-C single mismatches and multiple mismatches) (P=0.0004). Disease stage, GVHD-prophylaxis (T-cell depletion), CMV-status and HLA-incompatibility were the risk factors associated (all P0.005) with poor outcome. In the multivariate analysis, patients mismatched for loci other than HLA-C were at high risk of an adverse outcome (death: RR, 2.9; CI, 1.6–5.4, P=0.008, transplant-related mortality (TRM): RR, 3; CI, 1.5–5.9, P=0.0015). For patients mismatched for HLA-C only, the increased risk was of borderline significance (death: RR, 1.9; CI, 1–3.9, P=0.06, TRM: RR, 2.1; CI, 1–4.5, P=0.07). In spite of their lower expression, HLA-C antigens still represent relevant transplantation barriers that should be considered when searching for an unrelated donor.