Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies
Year: 2006
Type: article
Study design: Observational Study
Abstract: Failure to recognize the appropriate HLA class I ligands on the target cell triggers the inhibitory killer Ig-like receptors (KIR) to initiate cytotoxicity and may contribute to graft-vs.-leukemia (GVL) effect. Past studies have shown GVL advantage of the absence (incompatibility) of recipient HLA ligands to donor KIR genes in select patients (pts) undergoing myeloablative transplantation. Here we examine if similar advantage is seen in non-myeloablative transplant (NMT). The KIR-HLA ligand combinations studied were: KIR2DL1-Cw4 (Asn77Lys80); KIR2DL2/3-Cw3 (Ser77Asn80); KIR3DL1-Bw4; and KIR3DL2-A3/A11. The KIR typing was performed by rSSOP and HLA-C allele typing by SBT. Twenty-two lymphoid malignancy (LM) pts with ALL, HD, or NHL and 20 myeloid malignancy (MM) pts with AML or MDS were studied. The median age of LM and MM were both 45 years. All had relapsed/refractory disease, and/or co-morbidities precluding ablative transplantation. Peripheral blood hematopoietic stem cell graft from haploidentical family donors with alemtuzumab (20 mg × 5), fludarabine (30 mg/m2 × 4), and cyclophosphamide (500 mg/m2 × 4) regimen and mycophenolate ± cyclosporine ± in vitro alemtuzumab prophylaxis was used. Most donors were 3-4/6 HLA matched (75% in MM and 82% in LM). Each pair was evaluated for the donor KIR genotype and lack of corresponding class I ligands. Kaplan-Meier curves were compared using log-rank test. The impact of NK cell cytotoxicity was assessed by relapse related mortality (RRM). RRM in MM group was appreciably lower if there was KIR/HLA-C ligand incompatibility (P = .059). One year probability of RRM is 14% (95% confidence: 0-37%) in the incompatible group compared to 71% (95% confidence: 28-89%) in the compatible group (P = .059). In addition, RRM is lower though not reaching statistical significance (P = .070) if the incompatibility existed for 2 or 3 KIR/HLA ligand combinations (17%; 95% confidence: 0-42%) in comparison to no or 1 combination (66%; 95% confidence: 25-85%). There were no differences in RRM in LM group (P = .784 for HLA-C; P = .16 for Bw4; 0.752 for A3/11) with regard to KIR/HLA ligand matching. KIR-HLA ligand incompatibility did not increase the probability of grade 2-4 AGVHD in the MM group (P = .247 for HLA-C; P = .467 for Bw4; 0.357 for A3/11). These results suggest that KIR/HLA ligand incompatibility contributes to GVL effect without an increase in GVHD in high-risk pts with myeloid malignancy undergoing haploidentical NMT.
Institution: Duke Medical Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2016887368