Poor outcome in post transplant lymphoproliferative disorder with pulmonary involvement after allogeneic hematopoietic SCT: 13 years' experience in a single institute

Abstract

EBV-induced post transplant lymphoproliferative disorder (PTLD) continues to be a major complication after transplantation. Between January 1993 and April 2006, 12 cases of B-cell lymphoproliferative disorder were identified among 577 patients after allogeneic hematopoietic SCT (HSCT) with an overall incidence of 2.51% at 1 year. Grades II-IV acute GVHD, CMV antigenemia and the use of antithymocyte globulin (ATG) were independent risk factors for PTLD. At diagnosis, all of the tumors were CD20-positive and 11 (92%) were EBV-encoded RNA (EBER)-positive. Of the 12 patients with B-cell lymphoproliferative disorder, 8 had pulmonary involvement and 10 had extranodal involvement. Eleven patients received weekly rituximab therapy at a dose of 375 mg/m 2 ; the median interval between the onset of symptoms and rituximab therapy was 6 days. The overall mortality rate was 92% and seven (64%) of the deaths were directly attributable to disseminated PTLD within days or weeks of presentation. In our series, pulmonary PTLD followed an extremely aggressive course and poor response to current therapy, even though rituximab was included in the therapeutic regimens.

EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT

“…When progressing further, organ involvement is possible often featuring severe hepatitis, pneumonia, colitis, nephritis and variable symptoms associated with central nervous system manifestation. 5,27 In the laboratory, increasing levels of the lactate dehydrogenase regularly herald the clinical manifestation of PTLD. In cases of liver involvement, increased liver enzymes may be diagnosed as a surrogate of EBV hepatitis.…”

“…2,3 Published experience regarding the incidence of EBV-PTLD after allogeneic HCT ranges between 0.5 and 17% and is mainly based on single-centre experiences or retrospective studies limited by small numbers and diverse patient characteristics. [4][5][6][7] However, Landgren et al 8 collected data on 127 EBV-PTLD cases from 271 centres and found an elevated risk for developing PTLD especially in the first year after HCT (83%) with the highest occurrence during the first 6 months. However, late EBV-PTLD could be observed even up to 10 years after HCT.…”

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

“…1,[6][7][8][9][10][11][12] In the largest study to date, which included 26 901 allogeneic HCT recipients, the cumulative incidence of PTLD was 0.2% with no T-cell depletion, 2.8% with selective (B lymphocyte sparing) T lymphocyte depletion of grafts ex vivo and 1.7% in patients receiving ATG as in vivo T lymphocyte depletion for GvHD prophylaxis or treatment. 1 In the published studies, diagnostic criteria for PTLD and strategies for its prevention varied or were not described.…”

“…15 Mortality rates of PTLD have been reported between 50 and 100%, although it is not always clear whether PTLD was the primary or secondary cause of death, or an incidental finding at autopsy. 7,10,11,16 Mortality rates appear to be lower if intervention (tapering immunosuppression or administering rituximab or donor lymphocytes) occurs prophylactically (at a specified post transplant time point, irrespective of EBV reactivation) or preemptively (at the time of EBV viremia exceeding a threshold) rather than after PTLD has been diagnosed. 15 However, prophylactic or preemptive intervention subjects patients who would not develop PTLD to the side effects and costs of the intervention.…”

Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation

“…9, 13-15 PTLD with extranodal involvement carries worse prognosis than those with isolated lymphnode involvement, which might result from the difficulty in early diagnosis and low concentrations of medication distributed in affected tissues, 16, Downloaded by [University of Pennsylvania] at 13: 10 28 March 2016 progression and poorer survival. Our results also revealed that the patients with extranodal involvement were less responsive to rituximab than those with isolated lymphnode involvement, but had a higher response rate than those with extranodal involvement in reports, 14,18 which might be attributed to early diagnosis and prompt treatment as well as special medication approach. In our centers, EBV-DNA monitoring is routinely performed, which is helpful to early diagnose PTLD.…”