Abstract

Introduction Transplant associated microangiopathy (TMA) is a severe complication occurring after allogeneic stem cell transplantation(alloSCT). It is recognized to have a poor prognosis and no effective treatment has been defined.

Methods and Population In this study, we analysed the outcome of patients who developed TMA after alloSCT in our institution from 1996 to 2007. A total 199 patients underwent allogeneic transplantation. To diagnose TMA, we used the criteria proposed by the International Working group of TMA: > 4% schistocytes in blood, de novo or prolonged thrombocytopenia, sudden and persistent increase in lactate dehydrogenase concentration, decrease in serum haptoglobin and decreased haemoglobin.

Results From 1996 to 2006, the overall incidence of TMA in our institution was 19%(37/199). According to the type of transplant, the incidence of TMA was: 18%(14/79) for sibling myeloablative SCT(MSCT); 27%(10/37) for unrelated MSCT; 22.5%(9/40) in haploidentical SCT; 20%(2/10) for sibling non myeloablative SCT(NMSCT) and 20%(2/10) for unrelated NMSCT. Median age of patients was 37 years (range: 16–63). Male to female sex ratio was 1:1.8. As conditioning for transplantation, 60% of patients had received total body irradiation (49% for the alloSCT and 11% for previous treatments). At time of diagnosis of TMA, 35% of patients presented with neurological symptoms (unexplained headache, epilepsy, impaired concentration, drowsiness and/or confusion). Fourty-nine percent (49%) of patients also had cytomegalovirus reactivation; 54% were treated with steroids for acute Graft-versus-host disease and 100% of patients were treated with ciclosporine. The overall mortality rate in the TMA group was 86%, but TMA related mortality was 46%. In patients who died from TMA, median survival post-TMA diagnosis was 16 days(range: 4–60). 88% of those patients had been treated with plasma exchange, 12% by defibrotide. Four of the six patients(66%) treated with defibrotide died from haemorrhagic complications. Only 1 patient treated with defibrotide achieved a complete remission (CR). Of those patients who did not achieve complete remission, 65% had been conditioned with TBI versus 41% in patients who achieved CR.

Conclusion: In our series, the incidence of TMA is significant (19%). The most important risk factors of developing TMA are use of cyclosporine, steroid treatment, CMV reactivation, the use of TBI as conditioning and unrelated donor transplantation. From this study we are unable to define the most effective treatment for TMA. The use of defibrotide was associated with a high risk of haemorrhage in our series and should be used with caution. Because of its incidence and poor prognosis, randomized trials should be utilised to define effective treatment.

Author notes

Disclosure: No relevant conflicts of interest to declare.