High Incidence of Neurological Complications in Patients with Sickle Anemia Disease Undergoing Related Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Early Diagnosis and Treatment Can Chance the Prognosis
Authors: Helman Ricardo , Fernandes Juliana Folloni , Diniz Michelli Silva , Kerbauy Fabio R. , Kerbauy Lucila Nassif , Chapchap Eduardo Cerello , Brumatti Melina , Neves Nathalia da Silva Halley , Azambuja Alessandra Prandini , Kutner Jose Mauro , Ribeiro Andreza Feitosa , Hamerschlak Nelson 
Published: October 2019

Abstract
Introduction: Hematopoietic stem cell transplantation (HSCT) was offered primarily as a therapeutic option for severe sickle cell disease in the context of myeloablative matched sibling donor transplants over the last two decades and helped to establish the benefits of transplantation for this disorder. In recent years, the transplant community has set out to explore ways to make stem-cell transplantation more available to patients with the disease, define indications and better timing, and offset toxicities with novel approaches to conditioning and better supportive care. In this context, neurological complication such as stroke disease and blood flow alteration in medial cerebral artery constitute the main indications of HSCT but neurological complications are the main causes of TRM in D+100 and is important to find ways to prevent this problem.
Objective: Describe early neurological complications in sickle patients undergoing related HSCT on single specialized center and its following after the early diagnosis.
Material and Methods: Seven patient were undergone related HSCT for sickle disease from 2011 to 2013. All patients filled inclusion criteria in the study and signed agreement term.
Results: Seven HSCT were developed in the period, being four males. The average age was 13 years old (7-24). The HSCT indications were previous stroke, cerebral flow alteration on Doppler, acute chest syndrome and alloimunization. All patient were on blood transfusion therapy. The conditioning regimen was BuCy + ATG and the GVHD prophylaxis was MTX and CSA. Related donors were chosen with 10/10 HLA match and graft source marrow. The median of the neutrophil engraftment was D+ 25 and the platelets engraftment was in D+60. Two patient died, one by intestinal and liver GVHD on D+120, and another with sagittal sinus thrombosis and hemorrhagic stroke on D+3. Other two patients showed PRES syndrome related to cyclosporine use. The patients showed generalized seizures with tomographic neurological alteration. After the imunossupressor change to tacrolimus and the change of Phenytoin to Lamotrigine, the patient had total resolution of neurological complications without development of neurological sequelae. Patients who used Lamotrigine since the beginning of the conditioning have not shown neurological alterations.
Conclusion: The PRES Syndrome and Stroke are two of the main causes of mortality related to the use of calcineurin inhibitors. Patients with sickle disease have shown endothelial and cerebral microcirculation changes, which made them highly susceptible to neurological complication. The control of blood pressure, maintenance of 50.000 platelets level and the use of Lamotrigine as prophylaxis of seizures seems to decrease the risk of neurological complications. Prospective studies with lamotrigine as primary prevention of PRES Syndrome must be performed. Patients with severe neurological alteration as vessels stenosis more than 90% and Moya-Moya Syndrome must be better evaluated before the conditioning because of high TRM risk.

Disclosures
No relevant conflicts of interest to declare.