Frequency, characteristics, and outcome of PTLD after allo‐SCT: A multicenter study from the Spanish group of blood and marrow transplantation (GETH)

Abstract

on behalf of the Spanish group of blood and marrow transplantation (GETH) 15García-Cadenas and Yáñez equally contributed to this work. Abstract Post-transplant lymphoproliferative disorder (PTLD) is an infrequent complication of allogeneic stem cell transplant (allo-SCT). Aims: To estimate the frequency and management of PTLD in Spain and to identify prognostic factors influencing outcomes. Methods: Multicenter, retrospective analysis of allo-SCT performed in 14 transplant units over a 15-year period.Results: 102 PTLD were diagnosed among 12 641 allo-SCT, leading to an estimated frequency of 0.8%. PTLD was diagnosed at a median of 106 days after SCT. Eightyseven cases (85%) were diagnosed between 2007 and 2013. At diagnosis, 22% and 17% of the patients had gastrointestinal tract and CNS involvement. Eighty-seven (85%) received rituximab treatment, alone or in combination with immunosuppression reduction, with an ORR of 50.6%. With a median follow-up for survivors of 58 months, the 2-year overall survival (OS) was 33% and the PTLD-related mortality 45%. Age ≥ 40 years, malignant underlying disease, non-response to rituximab, and severe thrombocytopenia or lymphocytopenia at PTLD diagnosis were associated with worse overall survival. Conclusions:Only a small proportion of allografted patients were diagnosed a PTLD.Its clinical course was highly aggressive, and prognosis poor, especially in those failing rituximab. The prognostic impact found of the platelet, and lymphocyte count at diagnosis requires further confirmation. K E Y W O R D S allo-SCT, EBV, infection, PTLD, rituximab 466 | GARCÍA-CADENAS Et Al. 1 | INTRODUC TI ON Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) are an uncommon but potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Major risk factors for developing PTLD are T-cell depletion (TCD) of the graft, mismatched or unrelated donor (URD), umbilical cord blood transplantation and elderly patient age. 1-4The use of pre-emptive therapy with rituximab, triggered by positive results of routine monitoring of EBV DNAemia, has emerged as the preferred strategy for PTLD prevention in high-risk patients. [5][6][7][8] Additional therapeutic options (besides rituximab) for established PTLD include reduction of immunosuppression whenever feasible, chemotherapy or EBV-specific T cells, which have shown promising results but are often not available. [9][10][11][12][13] The early use of rituximab has surely reduced the rate of established PTLD and improved the short-term outcome in patients with PTLD, but there are concerns regarding its real impact on long-term survival. Death from PTLD in non-responders, relapse in responders, and infection-related mortality due to delayed B-and T-cell immune reconstitution all contribute to the low long-term survival. 14-16Until recently, most data analyzing the incidence of PTLD, its management, and prognosis after allo-SCT came from case reports or small single-center series. [17][18][1...

Refractory Epstein-Barr Virus (EBV)-Related Post-transplant Lymphoproliferative Disease: Cure by Combined Brentuximab Vedotin and Allogeneic EBV-Specific T-Lymphocytes

“…Following alloHSCT for hematologic disease, up to 11% of patients develop PTLD, with histopathology demonstrating DLBCL in ∼50% of the cases (2,3,11). In accordance with established risk factors (3,11), our patient was older than 40 years and had undergone MUD transplantation in serological EBV-mismatch. Further, the patient's history of CIBD including azathioprine treatment added to the risk of PTLD by augmented immunosuppression.…”

“…In our patient, the rapid onset and deterioration of PTLD symptoms and the non-responsiveness to rituximab, which has been reported in 30-50% of post-alloHSCT PTLD (2,4,11), characterized the highly aggressive PTLD course. Even polychemotherapy was ineffective, and, only after administration of the CD30-directed immunotoxin BV disease control could be achieved.…”

Characteristics, management, and outcome of pediatric patients with post‐transplant lymphoproliferative disease—A 20 years' experience from Austria

“…Several factors reportedly influence the prognosis of pediatric patients with PTLD. 13,36,60,[64][65][66][67][68][69][70][71][72][73] Parameters associated with a poor EFS or OS in our patient cohort, which may at least be partially owed to the relatively small number of patients included in our study.…”

Posttransplantation Lymphoproliferative Disease Treated by Retransplantation

“…e first-line treatment for PTLD is rituximab [4]. Patients who do not respond to this treatment have a particularly poor outcome, a 1-year overall survival of 14.6% has recently been reported [5]. Under these circumstances, adoptive EBV-specific T-cell therapy is an effective option [6].…”