Status of Donor-Recipient HLA Class I Ligands and Not the KIR Genotype Is Predictive for the Outcome of Unrelated Hematopoietic Stem Cell Transplantation in Beta-Thalassemia Patients

Giorgio La Nasa, Roberto Littera, Franco Locatelli, Claudio Giardini, Arianna Ventrella, Marina Mulargia, Adriana Vacca, Nicola Orrù, Sandro Orrù, Eugenia Piras, Giada Giustolisi, Daniela Lisini, Sonia Nesci, Giovanni Caocci, Carlo Carcassi

Research output: Contribution to journalArticlepeer-review

Abstract

Several studies have investigated the role played by killer immunoglobulin-like receptors (KIRs) and their ligands on the outcome of hematopoietic stem cell transplantation (HSCT) in patients affected by oncohematologic diseases. However, the interpretation of the results of these studies is considerably hampered by the heterogeneity of the diseases, disease status at transplantation, and the different protocols employed for both conditioning and graft-versus-host disease (GVHD) prophylaxis. To better define the role of KIRs in HSCT, we studied KIR genotypes and HLA class I ligands in a homogeneous group of 45 thalassemia patients transplanted with bone marrow cells from an HLA-identical, unrelated donor. Patients that were heterozygotes for HLA-Cw groups 1 (HLA-CwAsn80) and 2 (HLA-CwLys80) had a higher risk of developing acute GVHD than C1/C1 or C2/C2 homozygotes (relative risk [RR] = 8.75; 95% confidence interval [CI]: 1.63-46.76; P = .007). Vice versa, all patients who experienced primary/secondary graft failure were C1/C1 or C2/C2 homozygotes (RR = 20.45; 95% CI = 1.08-384.24; P = .009). Moreover, the presence of the HLA-A11 antigen conferred protection against GVHD (0% versus 35%, P = .02). Our results suggest that C1/C2 heterozygosity, may favor the development of donor alloreactivity and thereby increase the risk of GVHD. Conversely, C1/C1 and C2/C2 homozygosity seems to reduce the risk of GVHD but may increase the incidence of graft rejection. These data may be helpful in tailoring the intensity of GVHD prophylaxis and conditioning regimens in thalassemia patients receiving HSCT from an HLA-identical volunteer donor.

Original languageEnglish
Pages (from-to)1358-1368
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 2007

Keywords

  • KIR genotypes
  • KIR ligands
  • KIRS
  • NK cell alloreactivity
  • Thalassemia
  • Unrelated BMT

ASJC Scopus subject areas

  • Transplantation

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