Treatment of PTLD with Rituximab and CHOP Reduces the Risk of Renal Graft Impairment after Reduction of Immunosuppression

Abstract

We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (± rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of >1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup. Patients treated with IR + chemotherapy ± rituximab had a noninferior graft function compared with untreated controls suggesting that the negative impact of IR on the renal graft function can be fully compensated by the immunosuppressive effect of CHOP. The immunosuppressive effect of single agent rituximab may partially compensate the negative impact of IR on the graft function. Thus, it is possible to reduce immunosuppression when using chemotherapy to treat PTLD.

Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival

“…In line with this hypothesis, a recent study has reported that PTLD patients treated with reduction of immunosuppression þ chemotherapy had a noninferior eGFR 1 year down the lane as compared with untreated controls. 33 These two studies are in apparent contradiction with our results, but it should be mentioned that their follow-up period was shorter (13 and 12 months, respectively) and that they relied on surrogate end points for graft survival analysis (occurrence of rejection episode and variation of eGFR, respectively), whose reliability has already been criticized above. In contrast, our multivariate analysis did not identify rituximab or any other chemotherapy regimen as protective for the graft in the long term.…”

Post-transplant lymphoproliferative disorders

“…57 Some improvement in outcomes was reported for reduced intensity chemotherapy in paediatric population as well as for combination of reduction of immunosuppression with CHOP and rituximab. 69,70 The preliminary data regarding antiviral treatment with ganciclovir in combination with arginine butyrate are very promising, and it may become a standardized first or second-line treatment strategy in near future. 71,72 EBV-specific cytotoxic T-cell therapy was applied in 33 patients (most were SOT recipients) with EBV-positive refractory PTLD, with a 52% response rate at 6 months and 79% survival at 6 months, which is also very encouraging considering the patient population.…”

Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options

“…The antibody is generally well tolerated and rapidly induces the depletion of mature B-lymphocytes, reducing the compartment of EBVinfected cells, with an associated normalization of the viral load [50,80]. Initial results with rituximab combined with reduced immunosuppression or low dose chemotherapy (in a synchronous or sequential manner) have been promising [17,[81][82][83]. Rituximab has become the first line treatment option for PTLD.…”