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Central Nervous System Involvement in Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders after Allogeneic Hematopoietic Stem Cell Transplantation.
Transplantation and cellular therapy. 2021 March
Central nervous system (CNS) involvement in Epstein-Barr virus-related post-transplant lymphoproliferative disorders (EBV-PTLDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poorly defined. We analyzed the incidence, clinical and pathological characteristics, and impact on outcomes of EBV-PTLDs with CNS involvement (CNS-PTLDs) in 1009 consecutive adult patients undergoing allo-HSCT at a single-center institution. Four hundred eighty-two patients received matched sibling donor (MSD) transplants, 388 umbilical cord blood transplants (UCBTs), 56 matched unrelated donor (MUD) transplants, and 83 haploidentical transplants. We detected 25 cases of biopsy-proven EBV-PTLDs. Of these, nine patients (36%) had CNS-PTLDs: six after UCBT (67%), one after MSD transplantation (11%), one after MUD transplantation (11%), and one after haploidentical transplantation (11%). The 5-year cumulative incidence risk of CNS-PTLDs was 0.9%. Median time from transplant to CNS-PTLDs was 187 days, and all patients had neurological symptoms at diagnosis. Six out of the nine cases (67%) occurred with systemic involvement, and three cases (33%) had isolated CNS involvement. The most frequent histological subtype was monomorphic EBV-PTLD, and laboratory characteristics were similar to EBV-PTLDs without CNS involvement. We observed statistical differences in the rate of positive EBV DNA detection in plasma between isolated CNS-PTLDs (detection in one out of three, 33%) and the rest of the EBV-PTLDs (100%) (P = .01). Treatment strategies included chemotherapy, radiotherapy, and T cell therapy. However, seven out of nine patients died due to progression of the CNS-PTLDs at a median time of 17 days (range, 8 to 163) from diagnosis. The 5-years overall survival in patients who developed CNS-PTLDs was 22% (95% confidence interval [CI], 7% to 75%) and 5-year treatment-related mortality was 78% (95% CI, 51% to 100%), with no statistically significant differences between CNS-PTLDs and the rest of the EBV-PTLDs. In conclusion, despite advances in EBV monitoring and treatment strategies, CNS-PTLDs remain an uncommon but serious complication after allo-HSCT, with very poor prognosis.
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