Selecting the Optimal Unrelated Hematopoietic Stem Cell Transplant Donor for Relapse Prevention in Acute Myeloid Leukemia

Introduction/Background Hematopoietic cell transplantation (HCT) provides a cure for patients with acute myeloid leukemia. Natural killer cells (NK) play an important role in graft versus leukemia (GVL) effect after HCT, through killer immunoglobulin-like receptor (KIR) interaction with HLA ligands. This study is undertaken to validate our previously published mathematical model accounting for the KIR-KIRL interactions in a post HCT setting. Methods Retrospective data were obtained from the Center for International Blood and Marrow Transplant Registry for 2317 donor recipient pairs (DRP) who underwent 7/8 or 8/8 HLA allelic matched unrelated donor (URD) HCT for AML. KIR-HLA interaction scores were calculated by summing interaction values as previously described (Krieger et. Al BBMT 2019). Results Relapse risk was significantly reduced with donor-recipient pairs (DRP) with the higher inhibitory KIR-KIRL interaction and missing KIRL scores, Cox prop hazard, HR=0.86 (P=0.01) & HR=0.84 (P=0.02) respectively. The inhibitory KIR-KIRL interaction score components were then summed to give an IM-KIR score; IM KIR score =5 was also associated with a lower relapse risk, HR 0.8 (P=0.003). Subset analysis of 8/8 HLA matched patients showed further relapse reduction HR 0.75 (P=0.001); those patients with IM-KIR=5 donors who received ATG for in vivo T cell depletion (N=730) showed a 39% relapse reduction (HR 0.61, P=0.001) with a trend toward improved RFS, HR 0.84 (p=0.11). The use of ATG was shown to modify the effect of IM KIR score in interaction analysis (p=0.049), suggesting higher NK cell magnitude of KIR-KIRL interaction compensates for the general increase of relapse who receive in vivo T cell depletion. Conclusion This large international study confirms that unrelated DRPs with high iKIR and mKIR scores, as well as a combined IM-KIR scores confer significant relapse protection after MUD HCT, indicating that donors with a higher iKIR content may be considered optimal for URD HCT recipients with AML

Mapping the Spatial Deprivation of Pakistan

Geographical targeting may be a viable way to allocate resources for poverty alleviation in developing countries. Efficiency can be increased, and leakages to the nonpoor reduced substantially, by targeting needy areas. A national and regional database of substantial poverty maps or deprivation indices are not readily available in Pakistan. Further, existing activities of poverty alleviation are carried out on ad hoc basis in the absence of identified pockets of poverty. This paper presents indices of multiple deprivations based on the 1998 Population and Housing Census data. Possible applications of this exercise include identifying areas of need, making decisions on regional and sectoral priorities, facilitating targeted public interventions through special poverty alleviation programmes, understanding the relationship between poverty and its causes, and helping federal and provincial governments in determining financial awards.

On the Order of Gene Distribution on Chromosomes Across the Animal Kingdom

Background. The large-scale pattern of distribution of genes on the chromosomes in the known animal genomes is not well characterized. We hypothesized that individual genes will be distributed on chromosomes in a mathematically ordered manner across the animal kingdom. Results. Twenty-one animal genomes reported in the NCBI database were examined. Numerically, there was a trend towards increasing overall gene content with increasing size of the genome as reflected by the chromosomal complement. Gene frequency on individual chromosomes in each animal genome was analyzed and demonstrated uniformity of proportions within each animal with respect to both average gene frequency on individual chromosomes and gene distribution across the unique genomes. Further, average gene distribution across animal species followed a relationship whereby it was, approximately, inversely proportional to the square root of the number of chromosomes in the unique animal genomes, consistent with the notion that there is an ordered increase in gene dispersion as the complexity of the genome increased. To further corroborate these findings a derived measure, termed gene spacing on chromosomes correlated with gene frequency and gene distribution. Conclusion. As animal species have evolved, the distribution of their genes on individual chromosomes and within their genomes, when viewed on a large scale is not random, but follows a mathematically ordered process, such that as the complexity of the organism increases, the genes become less densely distributed on the chromosomes and more dispersed across the genome.Comment: 13 pages, 3 tables and 7 figure