title: Increased age-associated mortality risk in HLA-mismatched hematopoietic stem cell transplantation.
abstract: We investigated a possible interaction between age-associated risk and HLA-mismatch associated risk on prognosis in different age categories of recipients of unrelated hematopoietic stem cell transplants (HSCT) (n=3019). Patients over 55 years of age transplanted with 8/10 donors showed a mortality risk of 2.27 (CI 1.70-3.03,P<0.001) and 3.48 (CI 2.49-4.86,P<0.001) when compared to 10/10 matched patients in the same age group and to 10/10 matched patients aged 18-35 years, respectively. Compared to 10/10 matched transplantations within each age category, the Hazards Ratio for 8/10 matched transplantation was 1.14, 1.40 and 2.27 in patients aged 18-35 years, 36-55 and above 55 years. Modeling age as continuous variable showed different levels of risk attributed to age at the time of transplantation [OS: 10/10: Hazards Ratio 1.015 (per life year); 9/10: Hazards Ratio: 1.019; 8/10: Hazards Ratio 1.026]. The interaction term was significant for 8/10 transplantations (P=0.009). Findings for disease-free survival and transplant-related mortality were similar. Statistical models were stratified for diagnosis and included clinically relevant predictors except cytomegalovirus status and Karnofsky performance status. The risk conferred by age at the time of transplantation varies according to the number of HLA-mismatches and leads to a disproportional increase in risk for elderly patients, particularly with double mismatched donors. Our findings highlight the importance of HLA-matching, especially in patients over 55 years of age, as HLA-mismatches are less well tolerated in these patients. The interaction between age-associated risk and HLA-mismatches should be considered in donor selection and in the risk assessment of elderly HSCT recipients.
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg - Hessen, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fürst
authors.affiliation: Department of Hematology/Oncology, University of Leipzig, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Internal Medicine III, University of Ulm, Germany.
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.affiliation: Department of Medicine III, Johannes Gutenberg-University Mainz, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Wagner
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, University of Kiel, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.affiliation: Department of Hematology/Oncology, Georg-August-University Göttingen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Wulf
authors.affiliation: ZKRD-Zentrales Knochenmarkspender-Register für Deutschland (German National Bone Marrow Donor Registry), Ulm, Germany.|DRST - German Registry for Stem Cell Transplantation, Ulm, Germany.
authors.forename: Carlheinz R
authors.initials: CR
authors.lastname: Müller
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg - Hessen, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Neuchel
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg - Hessen, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Germany.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Tsamadou
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg - Hessen, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg - Hessen, Ulm, Germany j.mytilineos@blutspende.de.|Institute of Transfusion Medicine, University of Ulm, Germany.|DRST - German Registry for Stem Cell Transplantation, Ulm, Germany.
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006648:Histocompatibility / Q000235:genetics* / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D062486:Public Health Surveillance; D012307:Risk Factors; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens