Abstract
Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GvL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients.
Highlights
Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment for many hematological malignancies
In this study, we looked if activating killer-cell immunoglobulin-like receptors (KIR) genes in the HLAmatched related donors (RD) have any effect on relapse rate in transplanted patients
Longer relapse-free survival was observed in the patients receiving peripheral blood stem cells compared to the patients receiving bone marrow and in the patients with good prognosis compared to the patients with bad prognosis
Summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment for many hematological malignancies. The outcome of HSCT is strongly influenced by the genetic differences between donor/recipient pairs [1]. Genetic similarity or identity in the HLA genes in the major histocompatibility complex on chromosome 6, affects the incidence of graft-versushost disease (GvHD), the major complication of HSCT. Successful allogeneic HSCT, depends on T-cell mediated graft-versus-leukemia (GvL) effect, in which donor-derived T cells clear the remaining leukemic cells in patient. In addition to alloreactive T cells, donor-derived natural killer (NK) cells, are able to kill these malignant or virus-infected cells in the patient. NK cells might have a crucial role in relapse prevention by destroying remaining acute myeloblastic leukemia cells [2, 3]
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