B Cell Post Transplant Lymphoproliferative Disorder Complicating Solid Organ Transplantation (B-PTLD): A Single Centre Review Reporting 1) Results with Chemo-Immunotherapy (CHOP/R) and 2) the Predictive Ability of FDG-PET Scanning To Correlate with Long Term Overall Survival.
Authors: Tulpule Sameer , Mikhaeel George , Kazmi Majid , Nunan Tom , Van Der Walt John , Goldsmith David , Fields Paul A. 
Published: April 2020

Introduction: Post transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Treatment has proved difficult and includes dose reduction of immune suppression, combination chemotherapy, surgical excision and radiotherapy. Recently the monoclonal antibody Rituximab, has been added to the therapeutic choice, but how and when to use it is not clear. Previous studies have reported limited success with Rituximab alone plus decreased immune suppression (Choquet et al Blood2003:102:11, 986). We retrospectively analysed 40 patients who developed PTLD post-renal transplant.

Methods Patients were evaluated who received a renal transplant between 1981–2000. 30 patients were male and 10 female (median Age 46 years, range 21–70). The median time to development of PTLD was 54 months (range 1m–192m). Diagnostic samples were analysed by immunohistochemistry and clonality assessed by molecular analysis. For patients with monomorphic High grade histology an 18 FDG-PET scan was performed at diagnosis and an interim scan after 2 cycles of therapy (CHOP or CHOP/R, 21 day cycle). Treatment groups received a) no treatment due to rapidly progressive disseminated disease, b) decreased immune suppression alone, c) decreased immune suppression plus combination chemotherapy, d) decreased immune suppression plus single agent rituximab, e) decreased immune suppression plus combination chemo-immunotherapy (CHOP/R, all late B-PTLD &gt; 3 years), or f) surgery (n=1).

Results Median Overall survival for all patients was 15 months (range 0.5–96 months). For different patient groups according to treatment, median OS was as follows: For no treatment group (n=5, OS 2.5 months), for decreased immune suppression group (n=8, OS 53.5 months, all less aggressive polymorphic histology), for decreased immune suppression plus chemotherapy (n=16) median OS was 14 months, for the decreased immune suppression group plus single agent Rituximab (n=4) median OS 22months, for the decreased immune suppression group plus chemo immunotherapy (n=6) median OS is 34.5months (range 8–48months) with 6/6 (100%) patients alive and well in CR. No patients treated with CHOP/R suffered any adverse side effects or renal co-morbidity. 10 patients underwent an initial diagnostic PET scan and an interim PET scan .9/10 patients interim PET was negative and 1 patient obtained a PR which become negative at the end of treatment. All patients with a negative interim PET currently remain in CR (100%) at a median follow up of 30 months.

Conclusions The treatment of B-PTLD is difficult. Our series of patients now includes long term follow up on patients who either received Rituximab alone plus decreased immune suppression or chemo-immunotherapy plus decreased immune suppression. With a median follow up of 34.5 months, all CHOP/R treated patients are in CR. These results are encouraging and appear to offer significant improvement over previous treatments modalities i.e. chemotherapy only. For PTLD with high-grade histology a negative interim PET scan was highly predictive of prolonged OS and CR status.