Risk Factor Analysis for Thrombotic Microangiopathy after Reduced Intensity or Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.

Thrombotic microangiopathy (TMA) impairs long-term survival after allogeneic hematopoietic stem cell transplantation (HSCT). As the allogeneic HSCT procedure has developed, addressing risk factors for TMA has become more complicating. The aim of this study was to investigate the impact of transplant-associated factors on TMA incidence of in patients who underwent HSCT in various settings. One hundred and twenty-three consecutive allogeneic HSCT patients (15 to 69 years old) with hematologic diseases receiving myeloablative and reduced intensity conditioning were evaluated retrospectively. Of 123 HSCTs, 22 (17.9%) patients were diagnosed with TMA after HSCT. The median time to the diagnosis of TMA from HSCT was 33.5 days (range, 1–126). In 21of 22 patients, TMA occurred within 120 days after HSCT. Ten of 22 patients with TMA received some treatments for TMA. Any treatment for TMA including plasma exchange, tapering immunosuppressive agents, avoiding platelet transfusion, and administration with fresh frozen plasma and/or anti-thrombin III preparation, did not significantly improve overall survival in patients with TMA compared with those not treated for TMA. Using univariate Cox proportional hazard model analysis, age, HLA mismatch, GVHD grade II–IV, the use of FK506 for GVHD prophylaxis and the use of high-dose Bu were significantly associated with an increased incidence of TMA after HSCT. Furthermore, multivariate analysis showed the significance of GVHD grade II–IV, the use of FK506 and the use of high-dose Bu (16 mg/kg) persisted. On the other hand, the use of half-dose Bu (8 mg/kg) for conditioning was not significantly associated with increased TMA. The hazard ratios of the use of FK506, the use of high-dose Bu (16 mg/kg) and GVHD grade II–IV for TMA were 8.7 (95% CI 2.0–37), 5.7 (95% CI 1.5–21) and 3.4 (95% CI 1.3–9.1), respectively. In the present study, reduced intensity conditioning did not have an advantage over myeloablative conditioning for decreasing the incidence of TMA after HSCT. Our results also showed that high-dose Bu (16 mg/kg) for a conditioning and FK506 for a prophylaxis of GVHD might contributes more to TMA onset after HSCT than other agents.