Risk factors and appropriate therapeutic strategies for thrombotic microangiopathy after allogeneic HSCT

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, so far, no large cohort study determined the risk factors and the most effective therapeutic strategies for TA-TMA. Thus, the present study aimed to clarify these clinical aspects based on a large multicenter cohort. This retrospective cohort study was performed by the Kyoto Stem Cell Transplantation Group (KSCTG). A total of 2425 patients were enrolled from 14 institutions. All patients were aged ≥16 years, presented with hematological diseases, and received allo-HSCT after the year 2000. TA-TMA was observed in 121 patients (5.0%) on day 35 (median) and was clearly correlated with inferior overall survival (OS) (hazard ratio [HR], 4.93). Pre- and post-HSCT statistically significant risk factors identified by multivariate analyses included poorer performance status (HR, 1.69), HLA mismatch (HR, 2.17), acute graft-versus-host disease (aGVHD; grades 3-4) (HR, 4.02), Aspergillus infection (HR, 2.29), and veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS; HR, 4.47). The response rate and OS significantly better with the continuation or careful reduction of calcineurin inhibitors (CNI) than the conventional treatment strategy of switching from CNI to corticosteroids (response rate, 64.7% vs 20.0%). In summary, we identified the risk factors and the most appropriate therapeutic strategies for TA-TMA. The described treatment strategy could improve the outcomes of patients with TA-TMA in the future.

Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy

“…However, this assumption is complicated by well‐recognized response criteria of TA‐TMA. The majority of studies use decrease or normalization of LDH, absence of schistocytes, reduction or resolution of transfusion dependence, and 1‐year survival as an endpoints 38–40 . Half of the patients in the Sir group had normalization of LDH; however, some of the surviving patients did not have fast complete resolution of symptoms.…”

The impact of pre‐transplant anti‐HLA antibodies in transplants from HLA‐identical sibling donors: A multicenter study

“…Cytomegalovirus (CMV) or Epstein–Barr virus (EBV) reactivation was defined as a CMV DNA viral load >100 copies/mL or an EBV DNA viral load >100 copies/mL at any time after HSCT on at least 1 measurement 21 . Transplant‐associated thrombotic microangiopathy (TA‐TMA) was diagnosed in HSCT recipients with either histologic evidence of TMA on tissue sample or diagnostic markers appearing at the same time 22,23 . Relapse was defined as a recurrence of the underlying hematologic malignant disease.…”

Diagnosis and management of endothelial disorders following haematopoietic stem cell transplantation

“…3,7,15 Risk factors include age, donor type, more intensive conditioning regitmenssuch as those with TBI, CNI and mTORi, aGVHD, venous thromboembolic disease, ABO incompatibility, HLA mismatch and infection. 3,4,15,25 Clinical manifestations of endothelial damage in TA-TMA can occur in the kidney and multiple other organs. Renal injury, proteinuria and hypertension are common, with severe cases bearing proteinuria >30 mg/dL.…”

“…Risk factors include age, donor type, more intensive conditioning regitmens – such as those with TBI, CNI and mTORi, aGVHD, venous thromboembolic disease, ABO incompatibility, HLA mismatch and infection 3,4,15,25 …”