We evaluated the role of rituximab (R) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). A total of 465 patients were randomized to induction with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (every 3 weeks) or R-CHOP (R: 375 mg/m 2 intravenously, day 1). Those in complete remission (CR) or partial remission (PR) were randomized to maintenance with R (375 mg/m 2 intravenously once every 3 months for a maximum of 2 years) or observation. R-CHOP induction yielded an increased overall response rate (CHOP, 72.3%; R-CHOP, 85.1%; P < .001) and CR rate (CHOP, 15.6%; R-CHOP, 29.5%; P < .001). Median progressionfree survival (PFS) from first randomization was 20.2 months after CHOP versus 33.1 months after R-CHOP (hazard ratio [HR], 0.65; P < .001). Rituximab maintenance yielded a median PFS from second randomization of 51.5 months versus 14.9 months with observation (HR, 0.40; P < .001). Improved PFS was found both after induction with CHOP (HR, 0.30; P < .001) and R-CHOP (HR, 0.54; P ‫؍‬ .004). R maintenance also improved overall survival from second randomization: 85% at 3 years versus 77% with observation (HR, 0.52; P ‫؍‬ .011). This is the first trial showing that in relapsed/ resistant FL rituximab maintenance considerably improves PFS not only after CHOP but also after R-CHOP induction. IntroductionFor patients with follicular lymphoma (FL) chemotherapy alone has not resulted in improved overall survival (OS) over the past 30 years. [1][2][3][4] Although in most patients complete remissions (CRs) or partial remissions (PRs) can be obtained with either single agents or combination chemotherapy, the clinical course is characterized by a high relapse rate. After relapse, both the response rate and relapse-free survival after subsequent salvage treatment regimens steadily decrease, resulting in a median survival of only 4 to 5 years after first relapse. [5][6][7][8] Therefore, new treatment modalities resulting in increased progression-free survival (PFS) and OS are urgently required. Optimal treatment of patients relapsed after 1 or 2 chemotherapy regimens is largely unknown.Rituximab (R) is a chimeric murine/human anti-CD20 monoclonal antibody capable of killing CD20 ϩ lymphoma cells. Effector mechanisms include complement-mediated cytotoxicity, antibodydependent cellular cytotoxicity, and possibly direct induction of apoptosis. 9,10 In the nonrandomized pivotal study in 166 relapsed low-grade lymphoma patients, monotherapy with rituximab resulted in a response rate of 48%, with a 6% complete remission (CR) rate and a median time to progression in responding patients of 13 months. 11 Toxicity was generally mild to moderate (grade 1 or 2) and occurred primarily with the first infusion. 11 In a subsequent small phase 2 study, the combination of R with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was shown to be safe and effective. 12 Treatment results in FL might not only be improved by more effective induction...

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The diagnostic value of flow cytometry is more than twice that of cytomorphology. However, cytomorphologic examination of the CSF has additional diagnostic and possibly prognostic value, and should still be performed in conjunction with flow cytometry.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.