Post-transplant lymphoproliferative disorder (PTLD): single institutional experience of 141 patients

Abstract

BackgroundPost-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world.MethodsThis study was performed at University of Florida which is one of the largest transplant center in South East United States. We performed treatment and survival analysis along with univariate and multivariate analysis to identify prognostic factors.ResultsWe reviewed 141 patients diagnosed with PTLD over last 22 years with median follow-up of 2.4 years. The estimated median overall survival of the entire group was 15.0 years. Sub group analysis showed that 5-year overall survival rates of pediatric population were 88% (median not reached). For adults, median OS was 5.35 years while for elderly patients it was 1.32 years. The estimated median OS of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was 19.3 years. Univariate analysis identified gender, age at transplant and PTLD diagnosis, performance status, IPI score, allograft type, recipient EBV status, multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal site involvement, immunosuppressive drug regimen at diagnosis, initial treatment best response were statistically significant prognostic factors (p < 0.05). On multivariate analysis, age at PTLD diagnosis, recipient EBV status, bone marrow involvement, and initial best response were statistically significant prognostic factors (p < 0.05). Surprisingly, use of Rituximab alone as upfront therapy had poor hazard ratio in the cumulative group as well less aggressive PTLD subgroup comprising of early lesions and polymorphic PTLD.ConclusionsOur experience with treatment and analysis of outcomes does challenge current role of Rituximab use in treatment of PTLD. Currently as we define role of immunotherapy in cancer treatment, the role of acute rejections and immunosuppressant in PTLD becomes more relevant as noticed in our study. This study was also able to find new prognostic factors and also verified other known prognostic factors.

Non-Hodgkin lymphoma after liver and kidney transplantation in children. Experience from one center

“…Of special concern are patients with PTLD in whom chemotherapy complications may cause graft failure. 30 During the whole treatment process, none of our patients had any kind of graft insufficiency. Toxicity episodes were as expected following NHL chemotherapy and were all manageable.…”

“…Long-term outcome of monomorphic PTLD in children is estimated to be over 80%. 11,30 Patients with CNS and bone marrow involvement have inferior outcomes as compared to patients with lower disease stage as NHL in general population. 31 This was also observed in our study.…”

Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients

“…Short-term adverse effects are only part of the clinical picture of chemotherapy use. Historically, TRM rates for chemotherapy in PTLD patients were high 3 , 52 , 53 but more refined treatment approaches have improved survival, although chemotherapy TRM is still significant with rates between 8 and 13% 10 , 16 , 54 . For patients surviving chemotherapy, potential late-onset adverse effects (that persist or arise two or more years after CHOP chemotherapy treatment) are also likely a key driver of economic and humanistic burden.…”

Treatment dilemma for survivors of rituximab-induced bowel perforation in the setting of post-transplant lymphoproliferative disorder

“…Subsequent studies demonstrate mixed results regarding improved prognosis with rituximab 5. Because of the low incidence and complexity of the disease, data is sparse.…”

“…The cumulative incidence inclusive of all organ transplants is 1% at 18 months and almost 5% at 15 years 3. PTLD is the second most common malignancy after a solid organ transplant, following non-melanoma skin cancers, and about 70% of cases are associated with Epstein-Barr virus (EBV) 4 5. Due to multiple subtypes and low prevalence, data regarding optimum disease management is sparse.…”