Killer-Cell Immunoglobulin-like Receptor Diversity in an Admixed South American Population.

Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR). KIR genes are characterized by a high degree of diversity due to presence or absence, gene copy number and allelic polymorphism. The aim of this study was to establish the distribution of KIR genes and genotypes, to infer the most common haplotypes in an admixed Colombian population and to compare these KIR gene frequencies with some Central and South American populations and worldwide. A total of 161 individuals from Medellin, Colombia were included in the study. Genomic DNA was used for KIR and HLA genotyping. We analyzed only KIR gene-content (presence or absence) based on PCR-SSO. The KIR genotype, most common haplotypes and combinations of KIR and HLA ligands frequencies were estimated according to the presence or absence of KIR and HLA genes. Dendrograms, principal component (PC) analysis and Heatmap analysis based on genetic distance were constructed to compare KIR gene frequencies among Central and South American, worldwide and Amerindian populations. The 16 KIR genes analyzed were distributed in 37 different genotypes and the 7 most frequent KIR inferred haplotypes. Importantly, we found three new genotypes not previously reported in any other ethnic group. Our genetic distance, PC and Heatmap analysis revealed marked differences in the distribution of KIR gene frequencies in the Medellin population compared to worldwide populations. These differences occurred mainly in the activating KIR isoforms, which are more frequent in our population, particularly KIR3DS1. Finally, we observed unique structural patterns of genotypes, which evidences the potential diversity and variability of this gene family in our population, and the need for exhaustive genetic studies to expand our understanding of the KIR gene complex in Colombian populations.

High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma.

INTRODUCTION: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. MATERIAL AND METHODS: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). RESULTS: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). CONCLUSION: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.