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The aim of this study was to assess the efficacy of a gemcitabine-containing regimen in pretreated Hodgkin's lymphoma (HL) patients. Relapsed or refractory HL patients treated with gemcitabine, used alone or in combination with other cytotoxic agents, were retrospectively reviewed. Fifty-five patients were included in the study. Initial characteristics before gemcitabine administration were: Ann Arbor stage III-IV: 84%; International Prognostic Score less than 3 in 18/39 cases (46%); 31 primary refractory patients at the end of first-line therapy (56%); median number of previous chemotherapy regimens of 3. Twenty-nine patients received gemcitabine alone with a median maximal dose of 900 mg/m 2 per injection (range: 300-1500 mg/m 2 ). Gemcitabine was administered at a maximal dose of 1000 mg/m 2 per injection (range: 650-1250) in combination with vinorelbine in 10 patients, oxaliplatin in 13 patients, and other drugs in three patients, with a median of six injections (range: 1 -18). Reported toxicity was mainly hematologic. Overall response rate was 20% with 11% of complete remission. On univariate analysis, two adverse factors at progression were significant for response to gemcitabine-based regimen: stage III-IV disease and hemoglobin level was less than 10.5g/dl. This study demonstrated the limited efficacy of gemcitabine-containing regimen in heavily pretreated HL patients.

We observed in the same patient the development of a tonsil mucosa-associated lymphoid tissue-type lymphoma in 1994, a mediastinal Hodgkin's disease in 1998, and a colonic CD30+ anaplastic diffuse large B-cell lymphoma in 2000. A same-sized FR3-JH fragment was demonstrated by polymerase chain reaction, both at the level of total DNA and of single micromanipulated cells, showing monocytoid, Reed-Sternberg, or anaplastic morphology. Moreover, an identical IgH nucleotide sequence was detected in mucosa-associated lymphoid tissue-type lymphoma and colonic CD30+ anaplastic diffuse large B-cell lymphoma, whereas mediastinal Hodgkin's disease IgH rearrangement involved different VH and JH genes. CD30+ Reed-Sternberg and diffuse large B-cell lymphoma cells contained Epstein-Barr virus EBER sequences that were not observed at the level of mucosa-associated lymphoid tissue-type lymphoma. Therefore, Epstein-Barr virus infection may have played a role in diffuse large B-cell lymphoma transformation of mucosa-associated lymphoid tissue-type lymphoma and in the lymphomagenesis of Hodgkin's disease. In addition to their different clonal origin, Reed-Sternberg cells of Hodgkin's disease expressed a CD15+, CD20+ (rare cells), CD30+, Oct-2-, EBNA2-, LMP1+ phenotype, whereas anaplastic and Reed-Sternberg-like cells of diffuse large B-cell lymphoma were CD15-, CD20+, CD30+, Oct-2+, EBNA2+, and LMP1+. Interestingly, we also detected scattered CD30+ Epstein-Barr virus- large cells with prominent nucleoli in the initial tonsil mucosa-associated lymphoid tissue-type lymphoma, suggesting that these cells could be prone to Epstein-Barr virus infection and/or large cell transformation.