Characteristics of late transplant‐associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation

Abstract

Transplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.

The Role of Complement in HSCT-TMA: Basic Science to Clinical Practice

“…Furthermore, the timing of HSCT-TMA appears different between adult and pediatric patients. HSCT-TMA occurs early after transplantation in pediatric settings (typically within the first 28 days post-transplant), while in a study of adult patients, approximately half of HSCT-TMA events occurred “early” (within 100 days of transplant), and half occurred “late” (after 100 days post-transplant) and were often associated with chronic GvHD or late infections [ 11 , 82 ]. A recent study of adult patients undergoing allogenic HCT showed that HSCT-TMA in the absence of acute GvHD occurs earlier than 100 days, and that comorbid acute GvHD is a key risk factor for late-onset HSCT-TMA in adults [ 83 ].…”

Thrombotic Microangiopathy: Multi-Institutional Review of Pediatric Patients Who Underwent HSCT

“…In chronic GVHD, the endothelium can be damaged as a result of cytotoxic T-cell-induced injury [14]. Other studies have also shown that many of the immunosuppressive agents used to treat GVHD, such as calcineurin inhibitors and mTOR inhibitors, can cause damage to the endothelium [15,16]. Treatments given following transplant, such as radiation and chemotherapy, are also known to be associated with development of TA-TMA [17][18][19].…”

Transplant-Associated Thrombotic Microangiopathy in the Context of Allogenic Hematopoietic Stem Cell Transplantation: Where We Stand

“…TA-TMA is most often described as an early event in allo-HSCT with a time of onset between 32 and 86 days [ 17 , 18 ], although a recent study by Heybeli et al [ 19 ] documented a bimodal distribution of TA-TMA, with a first peak at day 27 and a second peak around day 200.…”

“…TA-TMA is considered one of the most severe complications of allo-HSCT [ 6 ]. Prognosis is generally poor with a case-fatality varying between 50 and 75% [ 6 , 19 ], underlying the need for early prognostic markers to be defined. The role of renal impairment in predicting lower survival rates has been well documented [ 18 , 20 , 21 ].…”