High-Dose Methotrexate and Cytarabine Chemotherapy May Be Effective and Safe in Solid Organ Transplant Recipients with Primary CNS Lymphomas (PCNSL)

Background: Post transplant lymphoproliferative disorder (PTLD), especially primary CNS lymphoma (PCNSL), is a serious complication of solid organ transplantation. Treatment has proved difficult and includes dose reduction of immune suppression (RIS), combination chemotherapy and radiotherapy. Recently the monoclonal antibody Rituximab, has been added to the therapeutic choice. Chemotherapy used in PCNSL is based on high-dose methotrexate (HDMTX), but need to be carefully monitored in adult patients (pts), especially with renal transplant. HDMTX could be associated with deleterious effects on renal graft function. We report here the results of HDMTX in pts with PCNSL after solid organ transplantation treated at the Institut de Cancérologie Gustave Roussy.

Methods: From February 2000, 18 pts with PTLD were referred to our Institute. 9 of them had PCNSL following renal (6), hepatic (1) or both renal and pancreatic (2) transplants. In all cases, RIS was not associated with PCNSL regression. Except in one case, all pts were treated with chemotherapy with HDMTX in 3-hour infusion. Folinic acid rescue was given IV every 6 hours (50 mg/m2) combined with alkaline hyper-hydration until MTX serum level was below 1 X 10–7 M. Immune suppressive therapy (IST) was reduced to solupred (10 mg/day) during chemotherapy and was reduced for 8 months after chemotherapy. 4 cycles of chemotherapy was planned and efficacy assessed every two cycles. If CR was reached with chemotherapy alone, no radiotherapy was delivered.

Results: From March 2007, 9 pts (4 males) developed PCNSL with a median of 6 years after transplant (1–26 years). Median age was 55 (range 33–70). PS was > 2 in 8/9 and 3 in one case. 8/9 pts had glomerular filtration rate > 60 ml/mn and received HDMTX without renal toxicity. One pt with GFR < 60 ml/mn was treated with 3 cycles of HD cytarabine + rituximab and adryamicin and is alive in complete remission (CR) 31 months after therapy. With a median follow up of 15 months, 4/9 pts are alive and in CR 45, 31, 29 and 7 months after therapy. 3 of them received radiotherapy. 5 pts died, 2 of lymphoma progression, 2 of chemotherapy toxicity (sepsis) and one of a gastric cancer. No graft rejection was observed.

Conclusions: our results suggest HDMTX can be given in pts with PCNSL and long term CR can be reached without graft failure. As chemotherapy regimens used for in those pts are in themselves immunosuppressive, IST may be reduced during chemotherapy without major risk.