Neurological complications of the central nervous system after allogeneic stem cell transplantation: the role of TA–TMA as a potential underreported cause.

Background neurological complications (NC), especially those of the central nervous system (CNS), represent a severe complication after allogeneic stem cell transplantation (allo-HSCT) and are associated with relevant morbidity and mortality. Objective we aim to characterize the potential risk factors for the development of CNS-NC with a special focus on the role of calcineurin inhibitors (CNI) as a predisposing factor. For this purpose, we compared Cyclosporin A (CsA) versus Tacrolimus (TAC) with respect to their influence on the incidence and type of CNS-NC after allo-HSCT. Study Design we retrospectively analyzed incidence, risk factors and impact on outcome of CNS-NC diagnosed during the post-transplantation follow-up in patients with different high-risk hematological malignancies who underwent allo-HSCT at our institution over a time frame of 20 years. All patients included in the analysis received CNI (CsA or TAC) as graft versus host disease (GVHD) prophylaxis. Results we evaluated a total of 739 consecutive patients transplanted from 12/1999 to 04/2019. Within a median follow-up period of 6.8 years, we observed a CNS-NC incidence of 17%. The development of CNS-NC was associated with decreased overall survival (OS) and increased transplant-related mortality (TRM). The most frequent CNS-NC were infections (30%) and neurological adverse events related to the administration of CNI, TAC or CsA, as GVHD prophylaxis (42%). In the multivariable analysis, age, total body irradiation (TBI) and severe acute and chronic GVHD significantly impacted as risk factors on the development of CNS-NC. TAC as compared with CsA emerged as an independent predisposing factor for CNS-NC. The TAC-associated risk of CNS-NC was mostly due to the occurrence of transplant-associated thrombotic microangiopathy (TA-TMA) with neurological manifestations (Neuro-TA-TMA), even if the general TA-TMA incidence was comparable in the two CNI subgroups. Conclusion CNS-NC are associated with poor prognosis after allo-HSCT with TAC emerging as a potential yet insufficiently characterized predisposing factor.