Reactions 1216 - 23 Aug 2008

SAntineoplastics

EBV-positive lymphoproliferative disorders: 3 casereports

Three patients developed Epstein-Barr virus (EBV)-positivelymphoproliferative disorders following treatment withalemtuzumab combined with CHOP* for T-cell lymphomas[durations of therapy to reaction onset not clearly stated].Patient 3 subsequently died. All patients were part of a phase IIstudy where three doses of alemtuzumab 30mg wereadministered with every CHOP cycle; CHOP cycles wereadministered at 14-day intervals [dosages not stated].

Patient 1, a 41-year-old man, received eight cycles ofalemtuzumab-CHOP ending in October 2006. His treatmentwas complicated with recurrent cytomegalovirus (CMV)reactivation (treated with ganciclovir) and neutropenic fever. ACT scan, in November 2006, showed a complete response totreatment. At this time his EBV DNA viral load had increased to3–10 × 103 copies/mL. He developed ulcerative duodenitis inDecember 2006. A CT scan, in January 2007, showed a tumourmass obstructing the duodenum loop; his EBV DNA levels hadincreased to 574 × 103 copies/mL. He received rituximabwithout effect. An EBV-encoded RNA (EBER)-positive T-celllymphoproliferative disorder was revealed by multiplebiopsies of the stomach and duodenum. There was a massiveaccumulation of EBER-positive and CD2+, CD3+ and CD5+,but CD4- and CD8- T-cells, which were oligoclonal. A biopsyof the tumour mass, in April 2007, showed an EBV-negative T-cell lymphoma distinct from the first. He receiveddexamethasone, cytarabine and cisplatin, but developedmassive haemophagocytic syndrome and died in July 2007.

Patient 2, a 32-year-old woman, received eight cycles ofalemtuzumab-CHOP ending in March 2006. She achievedcomplete remission. In August 2006 she experienced anepileptic seizure, after which, a large intracerebral mass wasbiopsied revealing CD20+ necrotic tumour cells. Serology forEBV was strongly positive and whole blood EBV viral load was< 2000 copies/mL. She received radiotherapy and rituximab.In November 2006 she developed CD20- pharyngeal diffuselarge B-cell lymphoma, which was strongly EBV-positive. Shereceived radiotherapy and prednisone. However, inAugust 2007, she developed subcutaneous skin lesionsshowing both a relapse in her original T-cell lymphoma and anEBV-positive lymphoproliferative disease. Despite refusingfurther treatment, in January 2008 she was found to beimproving with all of her subcutaneous lesions disappearingspontaneously. However her CD4 and CD8 counts remaineddepressed.

Patient 3, a 59-year-old man, received six cycles ofalemtuzumab-CHOP finishing in April 2006. Despite histreatment being complicated by recurrent CMV reactivation,he achieved complete remission. In April 2007, he beganreceiving foscarnet for CMV retinitis. He developed fever,dyspnoea, skin nodules, lymphadenopathy, splenomegaly,pleural fluid and ascites in December 2007. A subsequentlymph node biopsy revealed a relapse of his original T-celllymphoma as well as an EBV-positive CD20+ B-celllymphoproliferative disease. He died from this soon after.

Author comment: "A comparable lymphoproliferativedisorder may occur in the context of autoimmune disorderstreated with immunosuppressive or immunomodulatingagents. Here we report the occurrence of EBV-lymphoproliferative disease after strong suppressiveimmunochemotherapy consisting of alemtuzumab-CHOP forperipheral T-cell lymphoma."

* (Cyclophosphamide, doxorubicin [adriamycin], vincristine[Oncovin] and prednisone.)

Kluin-Nelemans HC, et al. EBV-positive immunodeficiency lymphoma afteralemtuzumab-CHOP therapy for peripheral T-cell lymphoma. Blood 112:1039-1041, No. 4, 15 Aug 2008 - Netherlands 801117499

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