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.
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.
La Nasa
Giorgio
G
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
Littera
Roberto
R
Locatelli
Franco
F
Giardini
Claudio
C
Ventrella
Arianna
A
Mulargia
Marina
M
Vacca
Adriana
A
Orrù
Nicola
N
Orrù
Sandro
S
Piras
Eugenia
E
Giustolisi
Giada
G
Lisini
Daniela
D
Nesci
Sonia
S
Caocci
Giovanni
G
Carcassi
Carlo
C
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*
D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015236:HLA-C Antigens; D054340:Receptors, KIR