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Previous Volume 346:235-242 January 24, 2002 Number 4 Next

Abstract PDF PDA Full Text PowerPoint Slide Set Editorial by Cheson, B. D. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

Methods Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients).

Results The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab.

Conclusions The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, is effective when given as a single agent in the treatment of relapsed or refractory indolent lymphomas and has activity in relapsed or refractory diffuse large-B-cell lymphoma.^12,13,14,15 CD20 is a cell-surface protein that occurs almost exclusively on mature B cells. The chimeric antibody is a human IgG1 in which the CD20-binding region was derived by genetic engineering from a mouse monoclonal antibody. On the basis of phase 2 studies in which rituximab in combination with CHOP had a good safety profile and induced responses in over 90 percent of patients with indolent or aggressive lymphoma,^16,17 the Groupe d'Etude des Lymphomes de l'Adulte (GELA) undertook a study to compare CHOP plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

Methods

Patients

Patients were eligible if they were 60 to 80 years of age and had untreated diffuse large-B-cell lymphoma that had been diagnosed according to the Revised European–American Lymphoma classification¹⁸ or the World Health Organization classification.¹⁹ Patients were required to have stage II, III, or IV disease and a performance status of 0 to 2 (good to fair) according to the criteria of the Eastern Clinical Oncology Group. Patients were not eligible if they had T-cell lymphoma, a history of indolent lymphoma, central nervous system involvement, active cancer, or any serious active concomitant disease or if, in the opinion of the investigator, their general status did not permit the administration of eight courses of CHOP. Patients were also excluded if they had a cardiac contraindication to doxorubicin therapy (e.g., abnormal contractility on echocardiography) or a neurologic contraindication to vincristine (e.g., peripheral neuropathy). Finally, patients with a positive serologic test for the human immunodeficiency virus or unresolved hepatitis B virus infection were also excluded.

This study complied with all provisions of the Declaration of Helsinki and its current amendments and was conducted in accordance with Good Clinical Practice guidelines.²⁰ All patients gave written informed consent. The protocol and informed-consent forms were approved by the local and national institutional review boards in each participating center and country. Study oversight was provided by an independent data and safety monitoring committee. The study investigators are listed in the Appendix.

Randomization

Eligible patients were randomly assigned by the study coordinating center to treatment with CHOP or CHOP plus rituximab. They were stratified according to center and age-adjusted International Prognostic Index scores (0 or 1 vs. 2 or 3, with a higher score indicating a higher risk of death), which are based on disease stage, performance status, and the lactate dehydrogenase level.² A panel of at least three hematopathologists conducted a central pathology review, without knowledge of the patients' outcome, to confirm the diagnosis of CD20-positive diffuse large-B-cell lymphoma.

Treatment

Patients treated with CHOP received the combination of 750 mg of cyclophosphamide per square meter of body-surface area on day 1; 50 mg of doxorubicin per square meter on day 1; 1.4 mg of vincristine per square meter, up to a maximal dose of 2 mg, on day 1; and 40 mg of prednisone per square meter per day for five days. They were treated every three weeks for eight cycles of CHOP. Patients treated with CHOP plus rituximab also received rituximab, at a dose of 375 mg per square meter, on day 1 of each of the eight cycles of CHOP. The rituximab infusion was interrupted in the event of fever, chills, edema, congestion of the head and neck mucosa, hypotension, or any other serious adverse event and was resumed when such an event was no longer occurring. No radiation therapy was scheduled or recommended at the end of treatment.

Patients who had grade 4 (severe) neutropenia or febrile neutropenia after any cycle of chemotherapy were given granulocyte colony-stimulating factor. If grade 4 neutropenia persisted during the next cycle, the doses of cyclophosphamide and doxorubicin were decreased by 50 percent. For patients with grade 3 (moderate) or 4 thrombocytopenia, the doses of cyclophosphamide and doxorubicin were decreased by 50 percent. If the neutrophil count was lower than 1500 per cubic millimeter or the platelet count was lower than 100,000 per cubic millimeter before a scheduled cycle, the cycle was delayed for up to two weeks, and then treatment was stopped. The doses of rituximab were not modified, but rituximab was discontinued when CHOP was stopped. Treatment was stopped if lymphoma progressed or the patient declined to continue or at the discretion of the investigator in cases of intercurrent illness or adverse events.

Response to Treatment and Adverse Events

Tumor responses were assessed after eight cycles of chemotherapy or at the end of treatment and were classified as complete response, unconfirmed complete response, partial response, stable disease, or progressive disease according to the International Workshop criteria.²¹ Complete response was defined as the disappearance of all lesions and of radiologic or biologic abnormalities observed at diagnosis and the absence of new lesions. An unconfirmed complete response was defined as a complete response with the persistence of some radiologic abnormalities, which had to have regressed in size by at least 75 percent. Partial response was defined as the regression of all measurable lesions by more than 50 percent, the disappearance of nonmeasurable lesions, and the absence of new lesions. Stable disease was defined as a regression of any measurable lesion by 50 percent or less or no change for the nonmeasurable lesions, but without growth of existing lesions or the appearance of new lesions. Progressive disease was defined as the appearance of a new lesion, any growth of the initial lesion by more than 25 percent, or growth of any measurable lesion that had regressed during treatment by more than 50 percent from its smallest dimensions.

All adverse events reported by the patient or observed by the investigator were collected from the case-report form in predefined categories. An adverse event was defined as any adverse change from the patient's base-line condition, whether it was considered related to treatment or not. Each event was graded according to the National Cancer Institute Common Toxicity Criteria grading system.²² All grade 3 and 4 events plus grade 2 infection were recorded in detail. Grade 1 and 2 adverse events were not extensively described.

Statistical Analysis

The sample size was calculated on the basis of the primary end point of event-free survival, and the number of patients required was based on the assumption of an exponential distribution of events. On the basis of the results of previous studies with CHOP in elderly patients, a conservative three-year event-free survival of 30 percent was assumed for the CHOP regimen.^23,24 To detect a change from 30 percent to 45 percent with the addition of rituximab, we calculated that 400 patients, recruited over three years and followed for a minimum of one year, would be required to provide the study with 80 percent power at an overall 5 percent significance level (two-sided, with an alpha level of 0.05). A single interim analysis of the primary efficacy outcome was planned; it included the 328 patients who underwent randomization before January 1, 2000.²⁵

Event-free and overall survival was analyzed by the log-rank test, and the results were expressed as Kaplan–Meier plots. A multivariate Cox regression analysis was performed to assess the effect of pretreatment prognostic factors (specifically, age, sex, number of extranodal sites, presence or absence of bone marrow involvement, beta₂-microglobulin level, serum albumin level, presence or absence of bulky disease, B symptoms [weight loss, fever, and night sweats]), and age-adjusted International Prognostic Index scores) on event-free and overall survival. Estimates of the treatment effect, after adjustment for these prognostic factors, are expressed as risk ratios for event-free and overall survival (CHOP plus rituximab as compared with CHOP), with 95 percent confidence intervals. Analyses of efficacy and safety included all randomized patients and followed the intention-to-treat principle. All P values are two-tailed. Statistical analyses were performed with SAS software (SAS Institute, Cary, N.C.) by the investigators at the GELA statistical office, without restrictions or outside control by the sponsor. The investigators had complete access to all study data.

Results

This study was conducted at 86 centers in France, Belgium, and Switzerland. A total of 399 patients were enrolled between July 1998 and March 2000, and 398 patients (202 in the CHOP-plus-rituximab group and 196 in the CHOP group) received at least one dose of protocol-specified treatment (1 patient was enrolled but died before treatment was administered).

Base-Line Characteristics

The median age of the patients was 69 years. There was no significant difference between the two groups in any clinical or pathological characteristic (Table 1). Prognosis was poor, which is consistent with the prognosis in elderly patients with aggressive lymphoma. Central pathological review was completed for 97 percent of patients; the results confirmed a diagnosis of diffuse large-B-cell lymphoma in 90 percent of those who could be assessed in the CHOP-plus-rituximab group and 85 percent in the CHOP group.

View this table: [in this window] [in a new window]   Table 1. Characteristics of the 399 Patients.

 
Treatment

The eight scheduled courses of chemotherapy were given to 72 percent of patients treated with CHOP and 80 percent of patients treated with CHOP plus rituximab. This difference was due to the number of patients who withdrew from the CHOP group because of disease progression: 23, as compared with 7 of those treated with CHOP plus rituximab. In each treatment cycle, more than 90 percent of the patients received at least 90 percent of the planned doses of doxorubicin and cyclophosphamide, with no significant difference between treatment groups in dose intensity for either drug in any cycle. In the CHOP-plus-rituximab group, more than 95 percent of the patients received the planned dose of rituximab.

Efficacy

With a median follow-up of 24 months, 86 events (progression, relapse, or death) were observed in the CHOP-plus-rituximab group and 120 in the CHOP group (in 43 percent and 61 percent of patients, respectively) (Table 2 and Figure 1). Event-free survival was significantly longer for patients treated with CHOP plus rituximab than for those treated with CHOP alone (P<0.001). According to the Cox analysis, the regimen of CHOP plus rituximab reduced the risk of events by 42 percent, as compared with the risk with CHOP alone (Table 2). The difference in event-free survival between the treatment groups was attributable to the higher number of patients in the CHOP group who had disease progression during treatment or with relapse. There was a significant benefit of CHOP plus rituximab over CHOP alone, both among patients with relatively low risk disease, indicated by a score of 0 or 1 on the International Prognostic Index (P<0.001), and those with high-risk disease, indicated by a score of 2 or 3 on the International Prognostic Index (P<0.03). Patients younger than 70 years and those 70 years or older, as well as the patients with diffuse large-B-cell lymphoma, had the same benefit from the combination of CHOP plus rituximab (data not shown).

View this table: [in this window] [in a new window]   Table 2. Results of the Intention-to-Treat Analysis of End Points.

 

View larger version (14K): [in this window] [in a new window]   Figure 1. Event-free Survival among 399 Patients Assigned to Chemotherapy with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) or with CHOP plus Rituximab.

 
A complete response or unconfirmed complete response was achieved in 76 percent of the patients treated with CHOP plus rituximab, as compared with 63 percent of those treated with CHOP alone (P=0.005) (Table 3). Disease progression during treatment was reported for 22 percent of patients in the CHOP group and 9 percent in the CHOP-plus-rituximab group. Prolongation of disease-free survival (complete remission) and progression-free survival in the CHOP-plus-rituximab group was of the same magnitude as the prolongation of event-free survival (data not shown). Survival was significantly longer for patients treated with CHOP plus rituximab than for those treated with CHOP alone (P=0.007): at two years, 70 percent of patients treated with CHOP plus rituximab were alive, as compared with 57 percent of those treated with CHOP alone (Table 2 and Figure 2).

View this table: [in this window] [in a new window]   Table 3. Response to Treatment with CHOP or CHOP plus Rituximab.

 

View larger version (13K): [in this window] [in a new window]   Figure 2. Overall Survival among 399 Patients Assigned to Chemotherapy with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) or with CHOP plus Rituximab.

 
Base-line prognostic factors were analyzed by multivariate Cox regression analysis. A high concentration (more than 3 mg per liter) of beta₂-microglobulin was identified as a negative prognostic factor in terms of both event-free and overall survival (risk ratio, 1.58 [95 percent confidence interval, 1.14 to 2.21] for death, disease progression, or another event and 1.82 [1.22 to 2.72] for death from any cause, respectively). The presence of more than one extranodal site of disease was another significant negative prognostic factor in terms of overall survival (risk ratio for death from any cause, 1.46). After adjustment for these prognostic factors, the risk ratio associated with treatment with CHOP plus rituximab, as compared with CHOP alone, was 0.55 (95 percent confidence interval, 0.41 to 0.75) for death, disease progression, or another event and 0.53 (0.37 to 0.77) for death from any cause, as compared with the unadjusted values of 0.58 (0.44 to 0.77) and 0.64 (0.45 to 0.89), respectively.

Adverse Effects

Table 4 presents all reported adverse events in each group. The grade 3 and 4 adverse events were consistent with the expected toxic effects of CHOP chemotherapy and occurred with similar frequency in both groups. Infection was one of the most frequent grade 3 or 4 adverse events in both groups. The difference in the incidence of cardiac events during treatment (47 percent for CHOP plus rituximab, as compared with 35 percent for CHOP) (Table 4) was due to a higher incidence of grade 1 events in the CHOP-plus-rituximab group than in the CHOP group (24 percent vs. 13 percent). This difference was consistent with the mild-to-moderate infusion-related events described in phase 2 studies of rituximab.^12,13,14,26 The incidence of grade 3 or 4 cardiac toxicity was the same in both groups (8 percent), with more reports of supraventricular arrhythmias and tachycardias in the CHOP-plus-rituximab group. Grade 3 or 4 cardiac failure or left ventricular dysfunction occurred in 18 patients in the CHOP-plus-rituximab group and 19 patients in the CHOP group.

View this table: [in this window] [in a new window]   Table 4. Nonhematologic Adverse Events Observed in Patients Treated with CHOP plus Rituximab or CHOP Alone.

 
Grade 3 or 4 adverse events related to the infusion of rituximab were observed in 19 patients in the CHOP-plus-rituximab group (9 percent); the most frequent of these were respiratory symptoms (with or without bronchospasm), chills, fever, and hypotension. In all cases, the symptoms disappeared after the infusion was slowed or stopped, and no patient died as a result of such an adverse event. All patients were able to receive further cycles of CHOP plus rituximab without recurrence of grade 3 or 4 infusion-related reactions.

Thirty-four patients (13 in the CHOP group and 21 in the CHOP-plus-rituximab group) died from causes not attributable to lymphoma; 23 died during the treatment period from infection (16 patients), cachexia (4 patients), or cardiovascular events (3 patients), without any significant difference between the groups. The remaining 11 patients (2 in the CHOP group and 9 in the CHOP-plus-rituximab group) died from infection (4 patients), cachexia (2 patients), cardiac disease (2 patients), suicide (1), another type of cancer (1), or gastrointestinal hemorrhage (1) while in a complete remission after completing therapy.

The median nadir of the neutrophil count after each cycle of chemotherapy was similar in both groups. After the first cycle, neutrophil counts fell to 400 per cubic millimeter in both groups. Thereafter, the median was slightly higher in the CHOP group than in the CHOP-plus-rituximab group. Neutropenia was not associated with an increase in episodes of infection during treatment, as shown in Table 4. The percentages of patients who required treatment with granulocyte colony-stimulating factor increased to a similar degree in each treatment group, to 37 percent for the fourth cycle and 43 percent for the eighth cycle. There were a few more cases of herpes zoster after treatment in patients receiving CHOP plus rituximab than in those receiving CHOP (nine vs. two, P=0.40). During treatment, 19 percent of patients receiving CHOP and 14 percent of those receiving CHOP plus rituximab had grade 3 or 4 anemia. The median nadir platelet counts remained above 130,000 per cubic millimeter in both treatment groups for all eight cycles.

Discussion

This randomized trial compared the efficacy and safety of rituximab in combination with CHOP chemotherapy with that of CHOP chemotherapy alone in elderly patients with diffuse large-B-cell lymphoma. We found higher response rates and improved event-free and overall survival among patients treated with the combination of rituximab and CHOP. The longer survival in the CHOP-plus-rituximab group was due to a lower rate of disease progression during therapy and fewer relapses among patients who had a complete response. Treatment with CHOP plus rituximab was well tolerated, and the incidence of severe or serious adverse events was no different from that in the CHOP group.

The event-free survival among elderly patients with diffuse large-B-cell lymphoma was only 12 to 18 months in previous randomized studies of chemotherapy.^6,9,24 We chose CHOP for use in this study because it is as effective as, and less toxic than, other, more recently developed chemotherapeutic regimens^5,27,28; it is also considered to be standard therapy for elderly patients with diffuse large-B-cell lymphoma.^6,11,29 The results with CHOP alone in our trial were similar to those previously reported in elderly patients.^{6,9,10,11,23,29} For this reason, we believe that the better results with CHOP plus rituximab are not attributable to an unusually poor outcome among patients in the CHOP group.

In a study comparing a regimen of doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVB) with CHOP in elderly patients, we found that ACVB was associated with longer event-free survival because patients who received ACVB had a lower incidence of relapses.²³ However, the rate of death due to toxic effects of the therapy was higher with ACVB than with CHOP, particularly in patients over 65 years of age, and for this reason, treatment with ACVB was not associated with prolonged survival.

In conclusion, the addition of rituximab to CHOP chemotherapy, given for eight cycles to elderly patients with newly diagnosed diffuse large-B-cell lymphoma, significantly increases the rate of complete response, decreases the rates of treatment failure and relapse, and improves event-free and overall survival as compared with standard CHOP alone. These gains were achieved without a significant increase in clinically significant toxic effects.

Supported by grants from Hoffmann–LaRoche.

Drs. Coiffier, Salles, Reyes, and Gisselbrecht have served as consultants to Roche, Genentech, or IDEC, the manufacturers of rituximab; have been members of speakers' bureaus sponsored by Roche, Genentech, or IDEC; or have done both for Roche, Genentech, or IDEC, as well as for other companies involved in the manufacture of antilymphoma drugs or other monoclonal antibodies.

Source Information

From the Hospices Civils de Lyon and the Université Claude Bernard, Lyons (B.C., G.S.); Hôpital Henri-Mondor, Paris (E.L., P.G., F.R.); Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis, Paris (J.B., C.G.); Hôpital de Hautepierre, Strasbourg (R.H.); the Centre Becquerel, Rouen (H.T.); the Institut Paoli-Calmette, Marseilles (R.B.); and the Centre Hospitalier de Lens (P.M.) — all in France; and the Université Catholique de Louvain, Brussels, Belgium (E.N.).

Pierre Lederlin, Ph.D., Centre Hospitalier Universitaire de Brabois, Nancy, France, was also an author.

Address reprint requests to Dr. Coiffier at the Service d'Hématologie, Centre Hospitalier Lyon-Sud, 69495 Pierre Bénite CEDEX, France, or at bertrand.coiffier{at}chu-lyon.fr.

References

1. Coiffier B. Non-Hodgkin's lymphomas. In: Cavalli F, Hansen HH, Kaye SB, eds. Textbook of medical oncology. London: Martin Dunitz, 1997:265-87. 
2. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993;329:987-994. [Free Full Text]
3. The Non-Hodgkin's Lymphoma Classification Project. Effect of age on the characteristics and clinical behavior of non-Hodgkin's lymphoma patients. Ann Oncol 1997;8:973-978. [Free Full Text]
4. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 1997;89:3909-3918. [Free Full Text]
5. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328:1002-1006. [Free Full Text]
6. Sonneveld P, de Ridder M, van der Lelie H, et al. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol 1995;13:2530-2539. [Abstract]
7. Dixon DO, Neilan B, Jones SE, et al. Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience. J Clin Oncol 1986;4:295-305. [Free Full Text]
8. Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol -- a Groupe d'Etude des Lymphomes de l'Adulte study. J Clin Oncol 2000;18:3025-3030. [Free Full Text]
9. Coiffier B. What treatment for elderly patients with aggressive lymphoma? Ann Oncol 1994;5:873-875. [Free Full Text]
10. Zinzani PL, Storti S, Zaccaria A, et al. Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 patients. Blood 1999;94:33-38. [Free Full Text]
11. Meyer RM, Browman GP, Samosh ML, et al. Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin's lymphoma. J Clin Oncol 1995;13:2386-2393. [Free Full Text]
12. Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 1997;90:2188-2195. [Free Full Text]
13. McLaughlin P, Grillo-Lopez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-2833. [Abstract]
14. Coiffier B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood 1998;92:1927-1932. [Free Full Text]
15. Foran JM, Rohatiner AZS, Cunningham D, et al. European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol 2000;18:317-324. [Erratum, J Clin Oncol 2000;18:2006.] [Free Full Text]
16. Czuczman MS, Grillo-Lopez AJ, White CA, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 1999;17:268-276. [Free Full Text]
17. Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol 2001;19:389-397. [Free Full Text]
18. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-1392. [Free Full Text]
19. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization classification of tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer, 2001.
20. Good clinical practice for trials on medicinal products in the European community. Good Clin Pract J 1994;1:Suppl.
21. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. J Clin Oncol 1999;17:1244-1244. [Erratum, J Clin Oncol 2000;18:2351.] [Free Full Text]
22. Cancer Therapy Evaluation Program. Common toxicity criteria, version 2.0. Bethesda, Md.: National Cancer Institute, March 1998.
23. Tilly H, Lepage E, Coiffier B, et al. A randomized comparison of ACVBP and CHOP in the treatment of advanced aggressive non-Hodgkin's lymphoma: the LNH93-5 study. Blood 2000;96:832a-832a.abstract 
24. Bastion YB, Blay JY, Divine M, et al. Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival -- a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years. J Clin Oncol 1997;15:2945-2953. [Abstract]
25. Coiffier B, Lepage E, Herbrecht R, et al. MabThera (rituximab) plus CHOP is superior to CHOP alone in elderly patients with diffuse large B-cell lymphoma (DLCL): interim results of a randomized GELA trial. Blood 2000;96:223a-223a.abstract 
26. Maloney DG, Liles TM, Czerwinski DK, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 1994;84:2457-2466. [Free Full Text]
27. Gordon LI, Harrington D, Andersen J, et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med 1992;327:1342-1349. [Abstract]
28. Jerkeman M, Anderson H, Cavallin-Stahl E, et al. CHOP versus MACOP-B in aggressive lymphoma -- a Nordic Lymphoma Group randomised trial. Ann Oncol 1999;10:1079-1086. [Free Full Text]
29. Tirelli U, Errante D, Van Glabbeke M, et al. CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. J Clin Oncol 1998;16:27-34. [Free Full Text]

The following persons and institutions participated in this GELA study: External advisory committee — E. Montserrat (chairman, Spain), M. Björkholm (Sweden), M. Buyse (Belgium), F. Cavalli (Switzerland), and M. Pfreundschuh (Germany); Pathological review committee — J. Brière, P. Gaulard, J. Bosq, J.F. Emile, B. Fabiani, and T. Petrella; Statistics — E. Lepage and N. Nio; Pharmacist — I. Madelaine; GELA clincial research — R. Chvetzoff; study centers (all in France, unless otherwise specified) — Centre Hospitalier Lyon-Sud, Pierre-Bénite — B. Coiffier and G. Salles; Hôpital de Hautepierre, Strasbourg — R. Herbrecht; Centre Becquerel, Rouen — H. Tilly; Centre Jean Bernard, Le Mans — P. Solal-Celigny; Institut Paoli Calmette, Marseilles — R. Bouabdallah; Centre Hospitalier Universitaire de Brabois, Nancy — P. Lederlin; Centre Léon Bérard, Lyons — C. Sebban; Institut Gustave Roussy, Villejuif — J.N. Munck and C. Fermé; Centre Hospitalier de Lens, Lens — P. Morel; Hôpital Henri Mondor, Creteil — F. Reyes and C. Haioun; Centre Hospitalier de Chambéry, Chambéry — M. Blanc; Hôpital Bon Secours, Metz — B. Christian; Centre Hospitalier Universitaire de Lille, Lille — B. Quesnel; Academisch Ziekenhuis Sint-Jan, Bruges, Belgium — A. van Hoof; Hôpital Saint-Louis, Paris — C. Gisselbrecht; Hôpital Purpan, Toulouse — M. Attal; Centre Hospitalier Universitaire Dupuytren, Limoges — D. Bordessoule; Hôpital Jean Bernard, Poitiers — V. Delwail; Université Catholique de Louvain, Ivoir, Belgium — A. Bosly; Centre Hospitalier Universitaire Clemenceau, Caen — M. Macro; Centre François Magendie, Pessac — G. Marit; Hôpital Pitié Salpétrière, Paris — J. Gabarre; Hôpital André Mignot, Le Chesnay — S. Castaigne; Centre Hospitalier Universitaire de Nîmes, Nîmes — E. Jourdan; Centre Hospitalier de la Durance, Avignon — E. Lepeu; Hôpital Pasteur, Colmar — B. Audhuy; Centre Antoine Lacassagne, Nice — A. Thyss; Clinique Pasteur, Evreux — N. Albin; Centre Médical Foch, Suresnes — E. Baumelou; Hôtel Dieu, Paris — A. Delmer; Centre Hospitalier de Brive, Brive — S. Lefort; Centre Hospitalier de Bourg en Bresse, Bourg en Bresse — H. Orfeuvre; Hôpital V. Prouvo, Roubaix — I. Plantier; Hôpital Bicêtre, Le Kremlin-Bicêtre — G. Tertian; Hôpital Necker, Paris — B. Varet; Hôpital Beclere, Clamart — F. Boué; Centre Hospitalier Universitaire de Dijon, Dijon — O. Casasnovas and D. Caillot; Université Catholique de Louvain, Brussels, Belgium — E. Van Den Neste; Institut Curie, Paris — D. Decaudin; Centre Hospitalier Universitaire Saint-Louis–Lariboisière, Paris — P. Brice, H. Dombret, J.P. Fermand, and J.M. Zini; Centre Hospitalier Universitaire de Liège, Liège, Belgium — G. Fillet; Fondation Drevon, Dijon — M. Flesch; Centre Hospitalier R. Dubos, Pontoise — Y. Kerneis; Centre Hospitalier d'Annecy, Annecy — C. Martin; Hôpital de Valence, Valence — P.Y. Péaud; Centre Hospitalier de Blois, Blois — P. Rodon; Centre Hospitalier Saint-Vincent, Lille — C. Rose; Hôtel Dieu, Clermont-Ferrand — P. Travade; Clinique Saint-Jean, Lyons — B. Velay; Hôpital de Bayonne, Bayonne — F. Bauduer; Centre Hospitalier de Libourne, Libourne — K. Bouabdallah; Hôpital Emile Muller, Mulhouse — J.C. Eisenmann; Hôpital Marc Jacquet, Melun — C. Kulekci; Centre Hospitalier Bois de l'Abbaye, Seraing, Belgium — S. Lampertz; Hôpital Inter Armées Percy, Clamart — G. Nedellec; Centre François Baclesse, Caen — A.M. Peny; Centre Hospitalier Victor Dupouy, Argenteuil — V. Pulik; Hôpital de Chalon, Chalon — B. Salles; Centre Hospitalier de Perpignan, Perpignan — X. Vallantin; Centre Hospitalier Robert Ballanger, Aulnay sous Bois — P. Agranat; Centre Hospitalier Universitaire de Nice, Nice — J.P. Cassuto; Centre Hospitalier Hutois, Huy, Belgium — J. Collignon; Centre Hospitalier de la Citadelle, Liège, Belgium — B. de Prijck; Hôpital Jolimont, Haine Saint Paul, Belgium — A. Delannoy; Centre Hospitalier Gilles de Corbeil, Corbeil Essonnes — A. Devidas; Hôpital La Fontonne, Antibes — J.F. Dor; Hôpital Cochin, Paris — F. Dreyfus; Clinique Saint Jean, Brussels, Belgium — C. Dubois; Clinique de Chaumont, Chaumont — G. Dupont; Centre Val d'Aurelle, Montpellier — M. Fabbro; Hôpital J. Monod, Le Havre — C. Fruchart; Clinique les Fougères, Dieppe — J.P. Gaillard; Centre Hospitalier Universitaire de Rennes, Rennes — B. Grosbois; Centre René Huguenin, Saint-Cloud — M. Janvier; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland — N. Ketterer; Centre Hospitalier du Val de Sambre, Sambreville, Belgium — C. Leroy; Clinique Saint Pierre, Ottignies, Belgium — M. Maerevoet; Hôpital des Canaux, Macon — F. Marechal; Hôpital Saint Joseph, Gilly, Belgium — P. Mineur; Hôpital Saint Joseph, Arlon, Belgium — P. Pierre; Centre Hospitalier Universitaire Nord, Marseilles — G. Sebahoun; Centre Hospitalier de Meaux, Meaux — C. Soussain; and Hôpital Nord, Amiens — C. Traulle.

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N Engl J Med 2002; 346:1830-1831, Jun 6, 2002. Correspondence

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• Sud, R., Friedberg, J. W. (2008). Salvage therapy for relapsed or refractory diffuse large B-cell lymphoma: impact of prior rituximab. haematol 93: 1776-1780 [Full Text]  
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• Ferreri, A. J.M., Dognini, G. P., Govi, S., Crocchiolo, R., Bouzani, M., Bollinger, C. R., D'Incan, M., Delaporte, E., Hamadani, M., Jardin, F., Martusewicz-Boros, M., Montanari, M., Szomor, A., Zucca, E., Cavalli, F., Ponzoni, M. (2008). Can Rituximab Change the Usually Dismal Prognosis of Patients With Intravascular Large B-Cell Lymphoma?. JCO 26: 5134-5136 [Full Text]  
• Ennishi, D., Takeuchi, K., Yokoyama, M., Asai, H., Mishima, Y., Terui, Y., Takahashi, S., Komatsu, H., Ikeda, K., Yamaguchi, M., Suzuki, R., Tanimoto, M., Hatake, K. (2008). CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. Ann Oncol 19: 1921-1926 [Abstract] [Full Text]  
• Wiernik, P. H., Lossos, I. S., Tuscano, J. M., Justice, G., Vose, J. M., Cole, C. E., Lam, W., McBride, K., Wride, K., Pietronigro, D., Takeshita, K., Ervin-Haynes, A., Zeldis, J. B., Habermann, T. M. (2008). Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma. JCO 26: 4952-4957 [Abstract] [Full Text]  
• Stolz, C., Hess, G., Hahnel, P. S., Grabellus, F., Hoffarth, S., Schmid, K. W., Schuler, M. (2008). Targeting Bcl-2 family proteins modulates the sensitivity of B-cell lymphoma to rituximab-induced apoptosis. Blood 112: 3312-3321 [Abstract] [Full Text]  
• Mori, A., Ibata, M., Mashiko, S., Tsutsumi, Y., Masauzi, N., Hashino, S., Morioka, M., Asaka, M., Imamura, M. (2008). Long-Term Administration of a Low-Molecular-Weight Heparin Contributed to Successful Treatment in a Patient With Primary Mediastinal Large B-Cell Lymphoma and Venous Thromboembolism. CLIN APPL THROMB HEMOST 14: 468-471 [Abstract]  
• Fu, K., Weisenburger, D. D., Choi, W. W.L., Perry, K. D., Smith, L. M., Shi, X., Hans, C. P., Greiner, T. C., Bierman, P. J., Bociek, R. G., Armitage, J. O., Chan, W. C., Vose, J. M. (2008). Addition of Rituximab to Standard Chemotherapy Improves the Survival of Both the Germinal Center B-Cell-Like and Non-Germinal Center B-Cell-Like Subtypes of Diffuse Large B-Cell Lymphoma. JCO 26: 4587-4594 [Abstract] [Full Text]  
• Habermann, T. M., Wang, S. S., Maurer, M. J., Morton, L. M., Lynch, C. F., Ansell, S. M., Hartge, P., Severson, R. K., Rothman, N., Davis, S., Geyer, S. M., Cozen, W., Chanock, S. J., Cerhan, J. R. (2008). Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era. Blood 112: 2694-2702 [Abstract] [Full Text]  
• Mead, G. M., Barrans, S. L., Qian, W., Walewski, J., Radford, J. A., Wolf, M., Clawson, S. M., Stenning, S. P., Yule, C. L., Jack, A. S., on behalf of the UK National Cancer Research Insti, (2008). A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood 112: 2248-2260 [Abstract] [Full Text]  
• Lecuyer, L., Chevret, S., Guidet, B., Aegerter, P., Martel, P., Schlemmer, B., Azoulay, E. (2008). Case volume and mortality in haematological patients with acute respiratory failure. Eur Respir J 32: 748-754 [Abstract] [Full Text]  
• King, J., Waxman, J., Stauss, H. (2008). Advances in tumour immunotherapy. QJM 101: 675-683 [Abstract] [Full Text]  
• Senff, N. J., Noordijk, E. M., Kim, Y. H., Bagot, M., Berti, E., Cerroni, L., Dummer, R., Duvic, M., Hoppe, R. T., Pimpinelli, N., Rosen, S. T., Vermeer, M. H., Whittaker, S., Willemze, R. (2008). European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood 112: 1600-1609 [Abstract] [Full Text]  
• Klapper, W., Szczepanowski, M., Burkhardt, B., Berger, H., Rosolowski, M., Bentink, S., Schwaenen, C., Wessendorf, S., Spang, R., Moller, P., Hansmann, M. L., Bernd, H.-W., Ott, G., Hummel, M., Stein, H., Loeffler, M., Trumper, L., Zimmermann, M., Reiter, A., Siebert, R., for the "Molecular Mechanisms in Malignant Lymphom, (2008). Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials. Blood 112: 1374-1381 [Abstract] [Full Text]  
• Cheson, B. D., Leonard, J. P. (2008). Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma. NEJM 359: 613-626 [Full Text]  
• Raetz, E. A., Cairo, M. S., Borowitz, M. J., Blaney, S. M., Krailo, M. D., Leil, T. A., Reid, J. M., Goldenberg, D. M., Wegener, W. A., Carroll, W. L., Adamson, P. C. (2008). Chemoimmunotherapy Reinduction With Epratuzumab in Children With Acute Lymphoblastic Leukemia in Marrow Relapse: A Children's Oncology Group Pilot Study. JCO 26: 3756-3762 [Abstract] [Full Text]  
• Tarella, C., Zanni, M., Magni, M., Benedetti, F., Patti, C., Barbui, T., Pileri, A., Boccadoro, M., Ciceri, F., Gallamini, A., Cortelazzo, S., Majolino, I., Mirto, S., Corradini, P., Passera, R., Pizzolo, G., Gianni, A. M., Rambaldi, A. (2008). Rituximab Improves the Efficacy of High-Dose Chemotherapy With Autograft for High-Risk Follicular and Diffuse Large B-Cell Lymphoma: A Multicenter Gruppo Italiano Terapie Innnovative nei Linfomi Survey. JCO 26: 3166-3175 [Abstract] [Full Text]  
• Shimada, K., Matsue, K., Yamamoto, K., Murase, T., Ichikawa, N., Okamoto, M., Niitsu, N., Kosugi, H., Tsukamoto, N., Miwa, H., Asaoku, H., Kikuchi, A., Matsumoto, M., Saburi, Y., Masaki, Y., Yamaguchi, M., Nakamura, S., Naoe, T., Kinoshita, T. (2008). Retrospective Analysis of Intravascular Large B-Cell Lymphoma Treated With Rituximab-Containing Chemotherapy As Reported by the IVL Study Group in Japan. JCO 26: 3189-3195 [Abstract] [Full Text]  
• Martin, P., Chadburn, A., Christos, P., Furman, R., Ruan, J., Joyce, M. A., Fusco, E., Glynn, P., Elstrom, R., Niesvizky, R., Feldman, E. J., Shore, T. B., Schuster, M. W., Ely, S., Knowles, D. M., Chen-Kiang, S., Coleman, M., Leonard, J. P. (2008). Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies. Ann Oncol 19: 1327-1330 [Abstract] [Full Text]  
• Dillon, R., Hirschfield, G. M, Allison, M. E D, Rege, K. P (2008). Fatal reactivation of hepatitis B after chemotherapy for lymphoma. BMJ 337: a423-a423 [Full Text]  
• Malumbres, R., Chen, J., Tibshirani, R., Johnson, N. A., Sehn, L. H., Natkunam, Y., Briones, J., Advani, R., Connors, J. M., Byrne, G. E., Levy, R., Gascoyne, R. D., Lossos, I. S. (2008). Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood 111: 5509-5514 [Abstract] [Full Text]  
• Targhetta, C., Cabras, M. G., Mamusa, A. M., Mascia, G., Angelucci, E. (2008). Hepatitis B virus-related liver disease in isolated anti-hepatitis B-core positive lymphoma patients receiving chemo- or chemo-immune therapy. haematol 93: 951-952 [Full Text]  
• Wilson, W. H., Dunleavy, K., Pittaluga, S., Hegde, U., Grant, N., Steinberg, S. M., Raffeld, M., Gutierrez, M., Chabner, B. A., Staudt, L., Jaffe, E. S., Janik, J. E. (2008). Phase II Study of Dose-Adjusted EPOCH and Rituximab in Untreated Diffuse Large B-Cell Lymphoma With Analysis of Germinal Center and Post-Germinal Center Biomarkers. JCO 26: 2717-2724 [Abstract] [Full Text]  
• Ychou, M., Azria, D., Menkarios, C., Faurous, P., Quenet, F., Saint-Aubert, B., Rouanet, P., Pelegrin, M., Bascoul-Mollevi, C., Guerreau, D., Saccavini, J.-C., Mach, J.-P., Artus, J.-C., Pelegrin, A. (2008). Adjuvant Radioimmunotherapy Trial with Iodine-131-Labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody F6 F(ab')2 after Resection of Liver Metastases from Colorectal Cancer. Clin. Cancer Res. 14: 3487-3493 [Abstract] [Full Text]  
• Persky, D. O., Unger, J. M., Spier, C. M., Stea, B., LeBlanc, M., McCarty, M. J., Rimsza, L. M., Fisher, R. I., Miller, T. P. (2008). Phase II Study of Rituximab Plus Three Cycles of CHOP and Involved-Field Radiotherapy for Patients With Limited-Stage Aggressive B-Cell Lymphoma: Southwest Oncology Group Study 0014. JCO 26: 2258-2263 [Abstract] [Full Text]  
• Crump, M., Coiffier, B., Jacobsen, E. D., Sun, L., Ricker, J. L., Xie, H., Frankel, S. R., Randolph, S. S., Cheson, B. D. (2008). Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol 19: 964-969 [Abstract] [Full Text]  
• Hsi, E. D., Steinle, R., Balasa, B., Szmania, S., Draksharapu, A., Shum, B. P., Huseni, M., Powers, D., Nanisetti, A., Zhang, Y., Rice, A. G., van Abbema, A., Wong, M., Liu, G., Zhan, F., Dillon, M., Chen, S., Rhodes, S., Fuh, F., Tsurushita, N., Kumar, S., Vexler, V., Shaughnessy, J. D. Jr., Barlogie, B., van Rhee, F., Hussein, M., Afar, D. E.H., Williams, M. B. (2008). CS1, a Potential New Therapeutic Antibody Target for the Treatment of Multiple Myeloma. Clin. Cancer Res. 14: 2775-2784 [Abstract] [Full Text]  
• Canellos, G. P. (2008). What Constitutes "Improved Prognosis"?. JCO 26: 1913-1914 [Full Text]  
• Oldham, R. K., Dillman, R. O. (2008). Monoclonal Antibodies in Cancer Therapy: 25 Years of Progress. JCO 26: 1774-1777 [Full Text]  
• Hoppe, B. S., Moskowitz, C. H., Filippa, D. A., Moskowitz, C. S., Kewalramani, T., Zelenetz, A. D., Yahalom, J. (2008). Involved-Field Radiotherapy Before High-Dose Therapy and Autologous Stem-Cell Rescue in Diffuse Large-Cell Lymphoma: Long-Term Disease Control and Toxicity. JCO 26: 1858-1864 [Abstract] [Full Text]  
• Thieblemont, C., Grossoeuvre, A., Houot, R., Broussais-Guillaumont, F., Salles, G., Traulle, C., Espinouse, D., Coiffier, B. (2008). Non-Hodgkin's lymphoma in very elderly patients over 80 years. A descriptive analysis of clinical presentation and outcome. Ann Oncol 19: 774-779 [Abstract] [Full Text]  
• Zinzani, P. L., Tani, M., Fanti, S., Stefoni, V., Musuraca, G., Castellucci, P., Marchi, E., Farsad, M., Fina, M., Pellegrini, C., Alinari, L., Derenzini, E., de Vivo, A., Bacci, F., Pileri, S., Baccarani, M. (2008). A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients. Ann Oncol 19: 769-773 [Abstract] [Full Text]  
• Lenz, G., Davis, R. E., Ngo, V. N., Lam, L., George, T. C., Wright, G. W., Dave, S. S., Zhao, H., Xu, W., Rosenwald, A., Ott, G., Muller-Hermelink, H. K., Gascoyne, R. D., Connors, J. M., Rimsza, L. M., Campo, E., Jaffe, E. S., Delabie, J., Smeland, E. B., Fisher, R. I., Chan, W. C., Staudt, L. M. (2008). Oncogenic CARD11 Mutations in Human Diffuse Large B Cell Lymphoma. Science 319: 1676-1679 [Abstract] [Full Text]  
• Pulte, D., Gondos, A., Brenner, H. (2008). Ongoing Improvement in Outcomes for Patients Diagnosed as Having Non-Hodgkin Lymphoma From the 1990s to the Early 21st Century. Arch Intern Med 168: 469-476 [Abstract] [Full Text]  
• Ellis, M., al-Ramadi, B., Finkelman, M., Hedstrom, U., Kristensen, J., Ali-Zadeh, H., Klingspor, L. (2008). Assessment of the clinical utility of serial {beta}-D-glucan concentrations in patients with persistent neutropenic fever. J Med Microbiol 57: 287-295 [Abstract] [Full Text]  
• Overman, M. J., Feng, L., Pro, B., McLaughlin, P., Hess, M., Samaniego, F., Younes, A., Romaguera, J. E., Hagemeister, F. B., Kwak, L., Cabanillas, F., Rodriguez, M. A., Fayad, L. E. (2008). The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma. Ann Oncol 19: 553-559 [Abstract] [Full Text]  
• Olejniczak, S. H., Hernandez-Ilizaliturri, F. J., Clements, J. L., Czuczman, M. S. (2008). Acquired Resistance to Rituximab Is Associated with Chemotherapy Resistance Resulting from Decreased Bax and Bak Expression. Clin. Cancer Res. 14: 1550-1560 [Abstract] [Full Text]  
• Czuczman, M. S., Olejniczak, S., Gowda, A., Kotowski, A., Binder, A., Kaur, H., Knight, J., Starostik, P., Deans, J., Hernandez-Ilizaliturri, F. J. (2008). Acquirement of Rituximab Resistance in Lymphoma Cell Lines Is Associated with Both Global CD20 Gene and Protein Down-Regulation Regulated at the Pretranscriptional and Posttranscriptional Levels. Clin. Cancer Res. 14: 1561-1570 [Abstract] [Full Text]  
• Ulaner, G. A., Colletti, P. M., Conti, P. S. (2008). B-Cell Non-Hodgkin Lymphoma: PET/CT Evaluation after 90Y-Ibritumomab Tiuxetan Radioimmunotherapy--Initial Experience. Radiology 246: 895-902 [Abstract] [Full Text]  
• Ryan, G., Martinelli, G., Kuper-Hommel, M., Tsang, R., Pruneri, G., Yuen, K., Roos, D., Lennard, A., Devizzi, L., Crabb, S., Hossfeld, D., Pratt, G., Dell'Olio, M., Choo, S. P., Bociek, R. G., Radford, J., Lade, S., Gianni, A. M., Zucca, E., Cavalli, F., Seymour, J. F. (2008). Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group. Ann Oncol 19: 233-241 [Abstract] [Full Text]  
• Doolittle, N. D., Abrey, L. E., Shenkier, T. N., Tali, S., Bromberg, J. E.C., Neuwelt, E. A., Soussain, C., Jahnke, K., Johnston, P., Illerhaus, G., Schiff, D., Batchelor, T., Montoto, S., Kraemer, D. F., Zucca, E. (2008). Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report. Blood 111: 1085-1093 [Abstract] [Full Text]