EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases

Abstract

We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (Po0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

“…The reported incidence of EBV DNA-emia ranging between 0.1-63% is largely dependent on the type of transplant, assay sensitivity, defined level of DNA-emia, use of systematic screening and its timing. [18][19][20][21][22][23][24][25][26][27] In a recent EBMT study, the overall incidence of PTLD after allogeneic HSCT was 3.2%, varying from 1.2% in matched family donor (MFD) to 2.8% in mismatched family donor (haploidentical/MMFD), 4.0% in matched unrelated donor (MUD), and 11.2% in mismatched unrelated donor (MMUD) recipients. 3 In recipients of unrelated cord blood (CBT), the incidence of EBV-PTLD was 2.6-3.3% for myeloablative transplants, and 7-12.9% in nonmyeloablative transplants.…”

“…3 In recipients of unrelated cord blood (CBT), the incidence of EBV-PTLD was 2.6-3.3% for myeloablative transplants, and 7-12.9% in nonmyeloablative transplants. 24,28 Interestingly, data from haplo-HSCT incorporating post-transplant cyclophosphamide (haplo-PTCy-HSCT) indicate a very low EBV-PTLD incidence. 23 The median time to development of EBV-PTLD after HSCT is 2-4 months.…”

“…21 Pooling results from published studies in HSCT recipients suggest that administration of rituximab results in a positive outcome for approximately 90% patients treated pre-emptively, and 65% with EBV-PTLD. 2,3,11,12,19,20,24,27,[51][52][53][54][55][56][57][58][59][60][61][62] Recent data demonstrate that RI, when applied in combination with rituximab, appears to improve the outcome by over 80%. 3 RI used alone as preemptive therapy resulted in a 68% success rate.…”

“…Risk factors for developing EBV-PTLD can be considered as existing pre- 20,24,[33][34][35] or developing post-transplant 7,[34][35][36][37] ( Table 3). Importantly, assessing the risk of EBV-PTLD is dependent on the HSCT context with potentially complex interactions between the primary hematological malignancy, HSCT procedure, source, and other factors.…”

High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation

“…Twenty-eight patients had grade III-IV disease (22 grade III, 6 grade IV) for a cumulative incidence of 25% (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] by day 180. The GI tract (either upper and/or lower tract) was the organ most commonly affected in 56 of 69 (81%) patients, followed by the skin (36 of 69, 52%), and the liver was the least commonly involved (9 of 69, 13%).…”