High mortality in hematopoietic stem cell transplant-associated thrombotic microangiopathy with and without concomitant acute graft-versus-host disease

Transplant-associated thrombotic microangiopathy (TA-TMA) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We hypothesized that TA-TMA correlates with steroid-refractory acute graft-vs.-host disease (aGvHD) and assessed 660 patients suffering from either AML n = 248, ALL n = 79, CML n = 23, CLL n = 36, lymphoma/myeloma n = 127, MDS/MPN n = 124 or bone marrow failure n = 22, who met the study inclusion criteria and had undergone myeloablative (78%) and non-myeloablative (22%) allo-HSCT between 2006 and 2016. Sixty-five (9.8%) of these patients matched the established diagnostic criteria for TA-TMA, and TA-TMA was shown to be a relevant independent risk factor for mortality (RR 3.27; 95% CI 2.07–5.16). Patients with TA-TMA and concomitant aGvHD had a markedly reduced OS compared to patients with TA-TMA or aGvHD alone (median 5.6 months vs. 7.6 months vs. 55.4 months, respectively; p < 0.0001). Risk factors for development of TA-TMA were aGvHD ≥ grade 2, higher aGvHD grade, steroid-refractory aGvHD, CMV reactivation/end-organ disease, but not the conditioning regimen (RIC or MAC), usage of TBI or TBI dose, underlying disease, donor type, age or sex. TA-TMA, with or without concomitant aGvHD, is a significant complication after allo-HSCT and a high-risk factor for a poor survival outcome. Thus, allo-HSCT recipients with grade 2–4 aGvHD or CMV viremia should be closely monitored for the presence of TA-TMA.