Posttransplant Lymphoproliferative Disorder Followed by Hodgkins Disease in a Renal Transplant Recipient

Abstract

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon but potentially fatal complication affecting 1% to 3% of renal transplant recipients. The term “PTLD” encompasses a spectrum of disorders ranging from polyclonal lymphoproliferation to monoclonal lymphomas, which are often Epstein-Barr virus (EBV) positive, aggressive B-cell non-Hodgkins lymphomas but Hodgkins lymphomas can also arise in this setting. We report a patient who developed mixed cellularity Hodgkins lymphoma 1 year after treatment for diffuse large B cell lymphoma arising post renal transplantation. A 34-year-old gentleman received a cadaveric renal transplant in August 1996 for end stage renal failure of unknown cause. Posttransplant immune suppression was with ciclosporin and prednisolone. He presented in September 2002 with a lump in the left axilla, which on further investigations was shown to be EBV positive high grade diffuse large B-cell lymphoma (stage IB). He went into remission with withdrawal of immune suppression and six courses of R-CHOP chemotherapy (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone) with subsequent radiotherapy to a residual lymph node mass in the left axilla. Immune suppression with ciclosporin and prednisolone was reinstituted in view of deteriorating renal function. In July 2004, he presented with sweats and progressively enlarging lymph nodes in the right axilla. A biopsy confirmed mixed cellularity Hodgkins disease. Some of the RS cells showed positivity for EBV. He was staged as having IB disease. He was treated with two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) in December 2004 and this was followed by radiotherapy to the right axilla in January 2005. He remains well and in complete remission 39 months posttreatment and has never suffered any episodes of graft rejection, though we have been unable to reduce the dose of prednisolone to less than 5 mg because of deterioration renal function. Hodgkin's lymphoma arising as a second PTLD, after treatment for an initial PTLD, is a very rare occurrence. There are only four such cases reported in literature, all occurring in the pediatric solid organ transplant setting. Initial PTLD was of the polymorphic subtype in three and “Hodgkins-like” in the fourth reported case (Table 1).TABLE 1: Clinical information of posttransplant Hodgkins lymphoma subsequent to other subtypes of PTLDThe treatment of Hodgkins disease after PTLD raises problems in terms of use of anthracylines and cardiotoxicity. In the four cases previously reported (Table 1), the PTLD had responded to withdrawal of immunosuppression or antiviral therapy and α interferon. Hodgkins disease was subsequently treated with cyclophosphamide, vincristine, prednisone and procarbazine/adriamycin, bleomycin and vinblastine in two cases, mechlorethamine, vincristine, prednisone, procarbazine in one case and unspecified chemotherapy in one case. One patient with recurrent Hodgkins disease had six cycles of ABVD. During relapse he had an unspecified number of cycles of ABVD after which adriamycin was substituted and bleomycin was stopped in view of cardiac and lung toxicity (5). De novo limited stage Hodgkins disease is normally treated with 4 to 6 cycles of combination therapy. Cardiac toxicity resulting from cumulative anthracycline therapy is generally seen at doses above 450 to 500 mg/m2. The cumulative anthracycline dosage our patient received with CHOP and ABVD chemotherapy was 400 mg/m2. In view of limited stage disease and concern about anthracycline induced cardiomyopathy, he discontinued chemotherapy after two cycles of ABVD, after which he received radiotherapy. Recommendations for managing similar patients cannot be made based on a single case. There is no evidence to suggest that chemotherapy for diffuse large B cell lymphoma increases the risk of subsequent Hodgkins disease. All the cases reported so far have responded to conventional chemotherapy though the long-term outcome in these patients is not known. Common clonality is suggested by the temporal relation between the non-Hodgkins lymphoma and Hodgkins disease and also because both tumors were EBV positive, though conclusive evidence for this is not available. Anand Lokare Sridhar Chaganti Department of Haematology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Graham Lipkin Department of Nephrology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Claudia Roberts Department of Cellular Pathology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom Prem Mahendra Department of Haematology University Hospital Birmingham NHS Foundation Trust Birmingham, United Kingdom