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HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism

, : HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood 113(12): 2851-2858

The finding that the risk of relapse in hematologic malignancy decreases after allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is considered to be frequently offset by graft-versus-host disease (GVHD). Thus, improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This cohort study registered 4643 patients with hematologic malignancies who received transplants from unrelated donors. Six major human leukocyte antigen (HLA) loci were retrospectively genotyped. We identified 4 HLA-Cw and 6 HLA-DPB1 mismatch combinations responsible for a decreased risk of relapse; of these, 8 of 10 combinations were different from those responsible for severe acute GVHD, including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of HLA-DPB1 were associated with a significantly better overall survival than were completely matched pairs. Moreover, several amino acid substitutions on specific positions responsible for a decreased risk of relapse were identified in HLA-Cw, but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism of the decreased risk of relapse on the basis of HLA molecule. Donor selection made in consideration of these results might allow the separation of GVL from acute GVHD, especially in HLA-DPB1 mismatch combinations.


PMID: 18997170

DOI: 10.1182/blood-2008-08-171934

Other references

Garret, R.; Ames, R.P., 1974: Alexander disease. Case report with electron microscopical studies and review of the literature. Archives of Pathology 98(6): 379-385

Levanon D.; Govrin Yehudain J.; Hirshowitz B., 1985: Collagen fiber alignment in the human preauricular dermis before and after rhytidectomy a scanning electron microscopic study. Ultramicroscopy 17(2): 164

Kretova, Vn, 1978: Electrification service in operation. Tekhnika v sel'skom khoziaistve: (3) 45-49

Harrison Sandy P.; Prentice I.C.lin; Sickel Kerstin, 2003: Direct impacts of atmospheric CO2 concentration on global vegetation distribution. The equilibrium vegetation model BIOME4 is used to explore the relative importance of the direct physiological impact of changes in atmospheric CO2 concentration [CO2] and in climate as experienced in the past and predicted for the future. Simulat...

Patel, N.; Roberts, G.; Levi Schaffer, F.; Habibi, P.; Lack, G., 2001: Food allergy and atopy are risk factors for life-threatening childhood asthma. Clinical & Experimental Allergy 31(1): 162, January

Schindler, E., 2004: Retirement of Gerhard Plodowski Gerhard Plodowski im Ruhestand. Natur und Museum (Frankfurt am Main). Dezember; 13412: 420-422

Weik, L.; Kaul, H.P.; Kubler, E.; Aufhammer, W., 2002: Grain yields of perennial grain crops in pure and mixed stands. Perennial grain crops were evaluated in pure stands and in various mixtures for their grain yield potential in, and suitability for, low-input systems on marginal land. The investigation was based on field experiments conducted at two sites charac...

Fricke, HW., 1980: Juvenile-adult colour patterns and coexistence in the territorial coral reef fish Pomacanthus imperator. In Eilat, Gulf of Akaba, Red Sea, territorial juveniles of the emperor fish P. imperator live within the territories of adult conspecifics. Field experiments with 2 wooden dummies, identical but for coloration showed that adults attacked mainly ad...

Li, T.; Zhi, H.; Luo, Y.; Chen, S., 1992: Studies of reform of yeast cell by protoplast fusion: V. Genetic analysis of the interspecific fusion hybrid between Saccharomyces cerevisiae and Saccharomyces diastaticus. The strain HU-KDF-185 tested is an interspecific triploid hybrid obtained by protoplast fusion of a diploid Saccharomyces cerevisiae and a haploid S. diastaticus. The following aspects were shown in the genetic analysis: (1) The strain HU-KDF-185...

Kline, J., 1978: I. An epidemiological review of the role of gravidity in spontaneous abortion. Early Human Development 1(4): 337-344