title: Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience.
abstract: Between June 1988 and May 1996, 428 patients underwent allogeneic BMT (288 related donor (RD) and 140 unrelated donor (UD)) at the Vancouver General Hospital. Eight patients (UD six and RD two) developed a post-transplant lymphoproliferative disorder (PTLD). Median age at BMT was 38 years (range 22-51). Five of the six UD allografts were T cell depleted. Cyclosporine+/-methotrexate was used for GVHD prophylaxis. All eight patients developed GVHD; in six this was refractory to treatment with corticosteroids. Rabbit antithymocyte globulin (ATG) or an anti-CD5-ricin A chain immunotoxin (Xomazyme) was used as second-line therapy for GVHD. Presentation with PTLD occurred at median day 90.5 (range 34-282) post BMT. Five of the eight patients had a rapidly progressive course characterized by fever, lymphadenopathy, lung and liver involvement and died within 3-8 days. PTLD was an incidental finding at post mortem examination in two patients. The remaining patient had localized disease and recovered. Pathological analysis revealed two morphological patterns; diffuse large B cell lymphoma (DLBC lymphoma, five patients) and polymorphous B cell hyperplasia (PBCH, three patients). EBV expression was positive in all eight cases and monoclonality was demonstrated in seven 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=0.006, RR=12.7) and acute GVHD grades 3-4 (P=0.04, RR=7.7) were the significant factors for development of PTLD. In conclusion, we have identified two forms of PTLD after BMT: one is characterized by disseminated disease with a rapidly progressive and often fulminant course and the other by localized, relatively indolent disease. Morphology, EBV positivity and clonality do not appear to correlate with the clinical course. The major risk factors for development of PTLD after BMT are ex vivo T cell depletion of the allograft and in vivo anti-T cell therapy for GVHD.
authors.affiliation: Division of Hematology, British Columbia Cancer Agency, Vancouver General Hospital, University of British Columbia, Canada.
authors.forename: I N
authors.initials: IN
authors.lastname: Micallef
authors.forename: M
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: R D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: J D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: H C
authors.initials: HC
authors.lastname: Fung
authors.forename: S H
authors.initials: SH
authors.lastname: Nantel
authors.forename: C L
authors.initials: CL
authors.lastname: Toze
authors.forename: H G
authors.initials: HG
authors.lastname: Klingemann
authors.forename: H J
authors.initials: HJ
authors.lastname: Sutherland
authors.forename: D E
authors.initials: DE
authors.lastname: Hogge
authors.forename: T J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: A
authors.initials: A
authors.lastname: Le
authors.forename: M J
authors.initials: MJ
authors.lastname: Barnett
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001955:British Columbia; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D012276:Ricin / Q000627:therapeutic use; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D000922:Immunotoxins; C059257:XomaZyme; D016572:Cyclosporine; D012276:Ricin