PB2333 TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY (TA-TMA): EXPERIENCE OF A SINGLE EUROPEAN COMPREHENSIVE CANCER CENTRE
Authors: A. Roque, C. Pinho Vaz, T. Nascimento, G. Brás, L. Leite, R. B. Ferreira, F. Campilho, S. Roncon, A. Campos
Journal: HemaSphere (2019)

Background: Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplantation (HSCT), usually associated with poor outcome. However, its diagnosis and treatment is difficult, with different series reporting conflicting results. Aims: To describe the incidence, aetiology, treatment, and outcome of TA-TMA in a cohort of patients (pts) submitted to allogeneic HSCT. Methods: Retrospective analysis of pts who underwent HSCT from 2010 to 2018, in our centre. TA-TMA diagnosis was based on criteria proposed by Cho et al (2010). The most likely aetiology was determined by reviewing the 2-week period before its onset. The aetiology of idiopathic or association to calcineurin inhibitors (CNI) was a diagnosis of exclusion. TMA resolution was defined as LDH < 1.5xLSN, platelet transfusion independence and no schistocytes in peripheral blood. A univariate and multivariate logistic regression was performed to evaluate the impact of clinical variables in TA-TMA onset. Overall survival(OS) was estimated using Kaplan-Meier survival function and compared using Cox proportional hazard regression (HR). Transplant-related mortality(TRM) include all non-relapse deaths. Results: Among 536 consecutive adult allogeneic HSCT recipients, 12 pts (2.2%) met the TA-TMA criteria, with a median onset time from HSCT of 83d (27-1236). Median age of pts with TA-TMA was 46 years(8-58), with 67% of female. In a univariate analysis only myeloablative conditioning (OR 4.16;p = 0.025) were significantly associated with TA-TMA development, which retains significance in a multivariate model that include all clinically meaningful variables (OR 8.06;p = 0.002). The most likely aetiologies (in the majority of cases ≥1) were graft-versus-host disease (GvHD) (n = 5), BKVirus haemorrhagic cystitis(n = 4), bacterial infection(n = 4), CNI(n = 3), and cytomegalovirus reactivation(n = 2). The main therapeutic approaches were CNI cessation/switch(n = 10), fresh frozen plasma(n = 9) (4 pts undergo plasmapheresis), rituximab(n = 2) and immunoglobulin(n = 1). The majority of TA-TMA pts had end-organ damage – 6 acute kidney injury, 4 neurologic deficit, with 7 need to be admitted in intensive care unit - and had a significant longer inpatient duration (41 vs 28d; p = 0.009). For a median follow-up of 189 days (159-1188), 6 pts (50%) achieved hematologic resolution. In our cohort, TA-TMA had a negative impact in OS, with a median OS of 6.3 and 47.9 months for pts with and without TA-TMA, respectively, although not statistically significant (HR 1.82;p = 0.074) (Fig. 1A). TA-TMA was a significant factor for TRM (HR 2.81; p = 0.003), with a mortality at 100 days post-HSCT of 8.3 (vs 3.7) (Fig. 1B). This impact remains significant in a multivariate model (HR 4.19;p < 0.001). In pts with TA-TMA, its resolution was significantly associated with a higher OS (65.7 vs 5.1 months; p < 0.001), while plasmapheresis (HR 5.74;p = 0.026) was associated with higher mortality, consistent with its negative impact on TA-TMA resolution (HR 0.20;p = 0.239), although not significant.Summary/Conclusion: In our cohort, there was a lower incidence of TA-TMA and a higher median time until its onset compared with literature. As described, myeloablative conditioning was independently associated with higher incidence of TA-TMA. Infection, GvHD and CNI were the main presumable causes. Surprisingly, plasmapheresis is associated with lower TA-TMA resolution rates and increased mortality. Our results confirm that TA-TMA is independently associated with increased and mortality (namely TRM) in pts submitted to allogeneic HSCT, irrespectively of pre-HSCT characteristics.