Abstract

AITL, as most T cell lymphomas, follows an aggressive clinical course with a 5-year overall survival of about 30%. Features consistent with B cell hyperstimulation including hypergammaglobulinemia with M component, autoimmune manifestations and B blast expansion in the tumoral tissue (sometimes culminating in overt B-cell lymphoma) are frequently seen. Clonal immunoglobulin gene rearrangements are detected in 20 to 40% of AITL. We postulated that AITL might benefit from a treatment with anti-CD20 monoclonal antibody (rituximab) combined to the standard CHOP regimen (R-CHOP). Between january 2001 et august 2004, 9 consecutive patients older than 60 years with newly diagnosed AITL were treated in our institution with a combination of rituximab (375mg/m2 given at day 1 of each cycle) and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone at day 1) chemotherapy delivered every 3 weeks. Patients were planned to receive 8 cycles, if a good response (at least partial response) was observed after the first 4 cycles. All patients presented characteristic features of AITL with generalized lymphadenopathy and poor performance status. Elevated LDH were seen in 6 patients. Four out of 9 patients had a serum M-component. Autoimmune hemolytic anemia was concomitantly diagnosed in 3 patients. Histopathological analysis revealed features of AITL in all cases associated with a significant expansion of large CD20+ B cells in 5 patients, CD10 positivity of tumor cells in 7 cases and EBV association in 5 cases (LMP-1 expression and/or EBER in situ hybridization positivity). DNA extracted from the biopsies was amplified using PCR and analyzed on a ABI 310 sequencing analyser. B and T-cell clonality analyses were performed according to the Biomed 2 procedure (Dongen et al. Leukemia 2003). Analysis of tumoral lymph node were available in 8 patients: a dominant T-cell clone was present in 5 cases, 2 of them showing also a dominant B-cell clone and 3 an oligoclonal B-cell repertoire. The 3 remaining cases had oligoclonal T-cell populations with a polyclonal B-cell repertoire. Eight patients achieved a complete remission at the end of treatment and one patient progressed after 3 cycles. Two patients relapsed at 13 and 14 months. Among these 3 refractory/relapsed patients, two were salvaged with additional treatment (alkylating agent alone or MabCampath). In July 2005, with a median follow-up of 12 months (7 to 53 months), all the patients are alive, 8 of them without evolutive disease. No additionnal toxicity was observed in this population of T-cell lymphoma patients as compared to that observed in elderly patients with diffuse large B-cell lymphoma treated with R-CHOP (Coiffier, N Engl J Med 2002). These results led us to consider that rituximab adjunction to CHOP could improve the prognosis of AITL in elderly patients. This approach is currently evaluated in an ongoing multicentric phase II study led by the GELA.

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