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.

Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation.

We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.

Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia.

Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.

Resultado del tratamiento de la púrpura trombocitopénica idiopática crónica con ácido ascórbico / Results of treatment in chronic idiopathic thrombocytopenic purpura with ascorbic acid

El objetivo de este trabajo es referir los resultados del tratamiento con ácido ascórbico en un grupo de enfermos con púrpura trombocitopénica idiopática crónica (PTIC) y resumir las experiencias de su empleo publicadas en la literatura respectiva. El grupo constó de trece enfermos refractarios a otras modalidades terapéuticas del trastorno, que recibieron ácido ascórbico 2g diariamente en la mañana por la vía bucal, durante un mínimo de ocho semanas. Al término del período de observación sólo cuatro enfermos (30 por ciento) experimentaron remisión parcial; en los demás no se demostró reacción favorable. Publicaciones previas informaron remisión completa y parcial en 11 y 19 por ciento respectivamnte en promedio. De acuerdo con tales resultados y los del presente estudio, se concluye que el empleo del ácido ascórbico carece de utilidad en el tratamiento de la PTIC