Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience

Between June 1988 and May 1996, 428 patients underwent allogeneic BMT (288 related donor (RD) and 140 unrelated donor (UD)) at the Vancouver General H ospital, Eight patients (UD six and RD two) developed a post-transplant lym phoproliferative disorder (PTLD), Median age at BMT was 38 years (range 22- 51), Five of the six UD allografts were T cell depleted. Cyclosporine +/- m ethotrexate was used for GVHD prophylaxis, All eight patients developed GVH D; in six this was refractory to treatment with corticosteroids. Rabbit ant ithymocyte globulin (ATG) or an anti-CD5-ricin A chain immunotoxin (Xomazym e) was used as second-line therapy for GVHD, Presentation with PTLD occurre d at median day 90.5 (range 34-282) post BMT, Five of the eight patients ha d a rapidly progressive course characterized by fever, lymphadenopathy, lun g and liver involvement and died within 3-8 days, PTLD was an incidental fi nding at post mortem examination in two patients. The remaining patient had localized disease and recovered. Pathological analysis revealed two morpho logical patterns; diffuse large B cell lymphoma (DLBC lymphoma, five patien ts) and polymorphous B cell hyperplasia (PBCH, three patients). EBV express ion was positive in all eight cases and monoclonality was demonstrated in s even cases, In multivariate analysis, T cell depletion of the allograft (P = 0.0001, relative risk (RR) = 30.5), anti-T cell therapy for GVHD (P = 0.0 06, RR = 12.7) and acute GVHD grades 3-4 (P = 0.04, RR = 7.7) were the sign ificant factors for development of PTLD, In conclusion, we have identified two forms of PTLD after BMT: one is characterized by disseminated disease w ith a rapidly progressive and often fulminant course and the other by local ized, relatively indolent disease, Morphology, EBV positivity and clonality do not appear to correlate with the clinical course, The major risk factor s for development of PTLD after BMT are ex vivo T cell depletion of the all ograft and in vivo anti-T cell therapy for GVHD.