title: 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.
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-Cw(Asn80)) and 2 (HLA-Cw(Lys80)) 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.
authors.affiliation: Cattedra di Ematologia, Centro Trapianti Midollo Osseo, Ospedale R. Binaghi-ASL 8, Dipartimento di Scienze Mediche Internistiche, Università di Cagliari, Cagliari, Italy. lanasa@tiscali.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.forename: Roberto
authors.initials: R
authors.lastname: Littera
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Giardini
authors.forename: Arianna
authors.initials: A
authors.lastname: Ventrella
authors.forename: Marina
authors.initials: M
authors.lastname: Mulargia
authors.forename: Adriana
authors.initials: A
authors.lastname: Vacca
authors.forename: Nicola
authors.initials: N
authors.lastname: Orrù
authors.forename: Sandro
authors.initials: S
authors.lastname: Orrù
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piras
authors.forename: Giada
authors.initials: G
authors.lastname: Giustolisi
authors.forename: Daniela
authors.initials: D
authors.lastname: Lisini
authors.forename: Sonia
authors.initials: S
authors.lastname: Nesci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D015236:HLA-C Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D054340:Receptors, KIR / Q000097:blood / Q000235:genetics*; D012189:Retrospective Studies; D014184:Transplantation, Homologous / Q000009:adverse effects; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
chemical_list: D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015236:HLA-C Antigens; D054340:Receptors, KIR