Richter's syndrome: biology and therapy.

Richter's syndrome, that is, transformation of chronic lymphocytic leukemia to a large cell or immunoblastic lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukemia. The onset of Richter's syndrome is characterized by worsening systemic symptoms, rapid tumor growth, and/or extranodal involvement. Median survival with conventional chemotherapy is less than 6 months. Therapy with more recent therapeutic regimens, such as hyperCVXD (fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone), augmented hyperCVXD, and yttrium-90 ibritumomab tiuxetan, has not produced major improvements in response rates or overall survival. Improvement in the outcome of patients with Richter's syndrome may be aided by a more comprehensive understanding of the pathogenesis of Richter's syndrome; therapy could then be targeted against specific abnormalities. Current data indicate that the transformation of chronic lymphocytic leukemia to a large-cell or immunoblastic lymphoma is associated with abnormalities in cell cycle regulation (e.g., loss of the cell cycle inhibitors p16(INK4a) and p27(KIP1) ) and DNA repair (e.g., mutations and/or deletions of the p53, ATM, and p14(ARF) genes and epigenetic silencing of the MLH1 gene). However, the critical event leading to transformation is unclear. Given the poor prognosis of patients with Richter's syndrome, every effort should be made to enroll these patients into clinical trials evaluating novel agents with the appropriate correlative studies.

Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms.

Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non-Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.

Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I

Este artículo describe el caso clínico de un enfermo con SIDA coinfectado por HTLV-1 que desarrolló un linfoma B del recto, variedad sarcoma inmunoblástico con diferenciación plasmacitoide. Las células malignas mostraron arreglo clonal de los genes de las CP (Jh) y CLk. La infección por el VEB fue demostrada serológicamente y por hibridación de un monitor específico con el ADN genómico de las células cancerosas. No se detectaron secuencias de HTLV-1 en el seno del tumor. Una remisión clínica completa, pero temporal, se obtuvo con siete ciclos de VACO-B. El enfermo abandonó el tratamiento y la sobrevida se desconoce.