Post-Renal Transplant De Novo Non-Skin Malignancies in Mycophenolate Mofetil- and Calcineurin Inhibitor-Based Immunosuppression.
Authors: Bachegowda Lohith , Gupta Diptesh , Bharadwaj Ajoy , Ranganna Karthik , Adamowicz TIM , Kumar Anil 
Published: October 2019

Abstract 1683

Poster Board I-709

Introduction- Post-transplant malignancy is one of the major complications of immunosuppression in kidney transplant recipients. Mycophenolate Mofetil(MMF) and Calcineurin inhibitors(CNI) based immunosuppression is a well established combination in clinical practice. MMF has an action on cell proliferation by inhibiting Inosine Mono Phosphate dehydrogenase. However, its antitumor properties have been constantly debated. It is shown to have some antiproliferative effects in leukemias and lymphomas with a decreased incidence of PTLD. This single center study evaluated the effect of combining mycophenolate mofetil (MMF) with calcineurin inhibitors on the incidence of de novo post-transplant non skin malignancies in renal transplant recipients. We also compared the incidence of solid versus liquid cancers.

Patients and Methods- Six hundred and fifty seven (657) consecutive kidney and kidney/pancreas recipients transplanted between January 2000 and December 2005 were analyzed for post-transplant malignancies. Three hundred and sixty two (362) recipients were maintained on a calcineurin inhibitor and MMF combination. The incidence of neoplasm in this group was monitored till June 2009.

All patients received induction therapy with basiliximab and methylprednisolone. Steroid therapy was discontinued after the second dose in the withdrawal group. In the steroid treated group oral prednisone was initiated on day 2 at 30 mg per day and rapidly tapered to 5 mg per day at one month and continued for the life of the graft. Maintenance therapy in all recipients included both, a calcineurin inhibitor and mycophenolate mofetil (MMF).

All clinical acute rejections were confirmed by biopsy and treated with intravenous methylprednisolone. Steroid unresponsive rejections were treated with Thymoglobulin

Table 1 shows the demography in the CNI + MMF recipient group Recipient demography Calcineurin inhibitor/MMF group Number of recipients 362 Mean age in years 53 ± 3 Male gender 196 Deceased donor kidney recipients 305 Mean HLA antigen mismatch 3.95 ± 2.6 Pre-transplant malignancies 0 Number of recipients with rejection 71 Table 2 Incidence and type of malignancies in calcineurin inhibitor + MMF group Type of cancer Calcineurin inhibitor/MMF group Total number of recipients 362 Post transplant lymphoproliferative disease 1 Hodgkin's lymphoma 1 Renal cell cancer 6 Lung cancer 3 Prostate cancer 2 Colon cancer 2 Breast cancer 2 Bladder cancer 1 Pancreatic cancer 1 Leukemia 1 Thyroid cancer 1 Total cancers 21 (5.8%)

Conclusion

In our study on CNI/MMF based immunosuppression in renal transplant patients, 5.8% developed various neoplasms. There was a lower incidence of hematologic- malignancies 3/362(0.8%) in comparison to solid organ neoplasm 18/362(4.97%). The incidence of PTLD was 0.27%, which is similar to other observational studies. This could partly be due to greater expression of Inosine Monophosphate, inhibited by MMF in malignant hematologic cells. Further multicenter analysis needs to be done to detect the incidence of liquid and solid neoplasms, correlating with intracellular IMP levels with MMF usage in renal transplant recipients.

Disclosures

No relevant conflicts of interest to declare.