Durable Remission After Aggressive Chemotherapy for Post-Cardiac Transplant Lymphoproliferation

Abstract

A frequently fatal complication of organ transplantation, post-transplant lymphoproliferative disorder (PTLD) develops in 2%-6% of cardiac recipients. Treatment remains poorly defined. Reduction in immunosuppression is effective in a proportion of cases, but mortality in the order of 80% is reported for patients requiring chemotherapy. The reason for such poor outcomes is unclear, but may be partly due to the concomitant use of immunosuppressives. An update report is provided on nineteen consecutive cardiac recipients with PTLD, studied retrospectively in terms of clinical features and outcome. Patients were managed according to a uniform treatment approach. Initial therapy was a trial of reduced immunosuppression with concomitant acyclovir followed, if unsuccessful, by aggressive combination chemotherapy. The regimen used was predominantly ProMACE-CytaBOM. Six patients with phenotypically polyclonal PTLD presented <6 months after transplantation (median 6 weeks). Only 1/4 (25%) treated patients responded to reduced immunosuppression; the remainder died of multiorgan failure. Thirteen patients presented with phenotypically monoclonal disease ≥6 months after transplantation. In 8/12 (75%) treated patients initial therapy was reduction in immunosuppression. None achieved CR; 2 experienced fatal rejection. Two patients achieved durable surgical CR. The remaining 8 patients received chemotherapy; 2/8 (25%) died during treatment, 6/8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of 64 months. Neutropenic sepsis, and subclinical doxorubicin cardiotoxicity at a mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate that aggressive chemotherapy is feasible and can produce very durable remissions in phenotypically monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well suited to cardiac recipients, minimizing doxorubicin exposure and obviating the need for concurrent immunosuppressives.