The potential role of HLA-DRB1*11 in the development and outcome of haematopoietic stem cell transplantation-associated thrombotic microangiopathy

Abstract

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) with high mortality rate. We retrospectively studied the frequency, clinical and genetic associations and prognostic effect of TA-TMA, in a total of 425 consecutive adult patients, who underwent allo-HSCT for a malignant haematological condition between 2007 and 2013 at our single centre. TA-TMA developed in 19% of the patients. Unrelated donor type (P o 0.001), acute GvHD grades II-IV (P o0.001), myeloablative conditioning regimens (P = 0.003), tacrolimus-based GvHD prophylaxis (P = 0.003), CMV infection (P = 0.003) and carriership for HLA-DRB1*11 (P = 0.034) were associated with the development of TA-TMA. Survival was adversely affected by the presence of TA-TMA (P o 0.001). Among patients with TA-TMA, the outcome of HLA-DRB1*11 carriers was significantly better compared with non-carriers (P = 0.003). As a new finding, our observations suggest that the presence of HLA-DRB1*11 antigen contributes to the development of TA-TMA and affects the outcome.

Risk and prognostic factors of transplantation‐associated thrombotic microangiopathy in allogeneic haematopoietic stem cell transplantation: a nested case control study

“…B cells, on the other hand, lead to tissue damage through antibody deposition and complement activation. [15] CMV viremia, however, has been found in fewer literatures to be a causal factor for TA-TMA. [2,15] The mechanism is unclear.…”

“…[15] CMV viremia, however, has been found in fewer literatures to be a causal factor for TA-TMA. [2,15] The mechanism is unclear. Evidence suggests that CMV could directly damage endothelial cells and cause platelet adhesion by inducing the expression of adhesion molecules and release of von Willebrand factor.…”

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

“…Other clinical predictors under consideration are infections. Certain more recent studies have emphasized on the association between infections and especially cytomegalovirus (CMV) and TA‐TMA . Although infections may be only a bystander in these immunocompromised patients, effective treatment is warranted to decrease morbidity and mortality in TA‐TMA patients.…”

Aktualitások a sérült immunitású betegek cytomegalovirusinfekcióinak ellátásában. I. Epidemiológia és klinikai szempontok

“…Saját intézményünkben végzett megfigyelések szerint az allogénőssejt-transzplantációval kezelt betegek körében a hCMV-reaktiváció 20%-os gyakorisággal fordul elő [47]. Ugyanakkor halálhoz vezető szervi betegség 178 elhunyt beteg post mortem vizsgálata alapján mindössze 12-ben (6,7%) volt igazolható [Sinkó J.…”