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Pharmacokinetics of 8 doses of rituximab (375 mg/m 2 ) given in combination with 2-week cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone/ prednisolone (CHOP-14) was determined by ELISA in 20 elderly patients with diffuse large B-cell lymphoma (DLBCL) 10 minutes before and after each infusion and 1 week and 1, 2, 3, 6, and 9 months after the last infusion. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling software (NONMEM VI). Concentration-time data were fitted into an open 2-compartment model and total clearance, central compartment volume, intercompartment clearance, and volume of distribution at steady-state (Vd ss ) were investigated. Total clearance was 9.43 mL/h and Vd ss was 9.61 l. Rituximab clearance was reduced (8.21 mL/h vs 12.68 mL/h; P ‫؍‬ .003) and elimination half-life was prolonged in women compared with men (t 1/2␤ ‫؍‬ 30.7 vs 24.7 days; P ‫؍‬ .003). Body weight also affected Vd ss (0.1 l increase of Vd ss per kilogram above median of 75 kg). A sexdependent effect and the higher weight of males contribute to their faster rituximab clearance, which might explain why elderly males benefit less from the addition of rituximab to CHOP than females. This trial was registered on www.clinicaltrials. gov as numbers NCT00052936, EU-20243

Summary. Chronic myeloid leukaemia (CML) is believed to represent a stem cell disorder involving all three cell lineages. The typical chromosomal aberration, the Philadelphia chromosome, is the translocation (9;22)(q34;q11). Several studies with cytogenetics, fluorescence in situ hybridization (FISH), or polymerase chain reaction have investigated the presence of the t(9;22) in different cell compartments. However, questions still remain. In six cases of CML we combined the standard May-Grü nwald-Giemsa staining with FISH at the single-cell level and were able to demonstrate that not only all maturation stages of granulopoiesis, erythropoiesis, and megakaryocytes, but also plasma cells, eosinophils, basophils and monocytes carried the Philadelphia chromosome in 53-98% of samples. Using immunological identification of single cells we were able to demonstrate that the t(9;22) is detectable in 34% of CD3-positive T lymphocytes, in 32% of CD19-positive B lymphocytes, and in 82% of CD34-positive precursor cells. The results give new insight into the biology of CML and may have implications for future therapeutic strategies.

Although little progress has been made in the treatment of follicular lymphomas (FL) within the last few decades, several new therapeutic modalities have recently demonstrated promising activity. These include myeloablative therapy followed by autologous stem cell transplantation in younger patients in first remission revealing a significant prolongation of remission duration in three prospective randomized trials, whereas the impact on overall survival still needs to be determined. Adding the anti-CD20 antibody rituximab to conventional chemotherapy resulted in a significant increase in remission rate, remission duration and in two of four currently available prospective randomized studies even in a longer overall survival. A prolongation of remission duration was also seen when rituximab was administered as maintenance after cytoreductive therapy or by prolonged application as a single agent. Radioimmunotherapy (RIT) with radioisotopes coupled to monoclonal antibodies revealed encouraging data in several phase II studies. Prospective randomized studies are warranted, however, to define the impact of RIT on FL therapy. New therapeutic perspectives also emerge from increasing insights into the biology of the disease that unravel molecular targets for novel agents, some of which have entered clinical evaluation already.

BACKGROUND.In patients with advanced‐stage follicular lymphoma (FL) and mantle cell lymphoma (MCL), conventional chemotherapy remains a noncurative approach, and no major improvement in overall survival has been achieved in recent decades.METHODS.The German Low‐Grade Lymphoma Study Group performed a randomized trial comparing combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy with combined mitoxantrone, chlorambucil, and prednisone (MCP) chemotherapy as first‐line therapy for patients with advanced‐stage FL or MCL.RESULTS.Three hundred sixty‐three patients with advanced‐stage FL (n = 277 patients) or MCL (n = 86 patients) entered the trial and were evaluable fully. CHOP resulted in a significantly higher overall response rate in patients with FL (91% vs. 82%; P = .026) and a similar tendency in patients with MCL (87% vs. 73%; P = .080). However, no significant differences were observed in the time to treatment failure or in overall survival. CHOP produced significantly more nonhematologic toxicities, whereas MCP was associated with more severe hematologic side effects. The proportion of patients who successfully underwent peripheral blood stem cell collection was significantly lower after MCP (44% vs. 93% after CHOP; P = .0003).CONCLUSIONS.Taking into account that, currently, chemotherapy regularly is combined with rituximab as first‐line therapy for FL and MCL, the data from this study may have an impact on the type of chemotherapy to be applied in such combinations. Particularly in younger, high‐risk patients who are candidates for autologous stem cell transplantation, CHOP should be preferred over MCP. Cancer 2006. © 2006 American Cancer Society.