Treatment of AIDS-related lymphomas: rituximab is beneficial even in severely immunosuppressed patients
Wyen, Christopha; Jensen, Björnb; Hentrich, Marcusc; Siehl, Jand; Sabranski, Michaele; Esser, Stefanf; Gillor, Daniela; Müller, Markusg; Van Lunzen, Janh; Wolf, Timoi; Bogner, Johannes R.j; Wasmuth, Jan C.k; Christ, Hildegardl; Fätkenheuer, Gerda; Hoffmann, Christianm,n
aFirst Department of Internal Medicine, University of Cologne, Cologne
bDepartment of Gastroenterology, Hepatology and Infectiology, Düsseldorf University Hospital, Düsseldorf
cDepartment of Hematology and Oncology, Hospital Harlaching, Munich
dÄrzteforum Seestrasse, Berlin
eIFI Institute for Interdisciplinary Medicine, Hamburg
fDepartment of Dermatology, University of Essen, Essen
gDepartment of Internal Medicine, Vivantes Klinikum Neukölln, Berlin
hDepartment of Internal Medicine, University of Hamburg-Eppendorf, Hamburg
iDepartment of Internal Medicine, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main
jDepartment of Internal Medicine, University of Munich, Munich
kDepartment of Internal Medicine I, University of Bonn, Bonn
lInstitute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne
mIPM Study Center, Hamburg
nUniversity of Schleswig-Holstein, Kiel, Germany.
Correspondence to Dr Christoph Wyen, MD, First Department of Internal Medicine, University Hospital of Cologne, Joseph Stelzmann Street 9, 50924 Cologne, Germany. Tel: +49 221 478 3324; fax: +49 221 478 5915; e-mail: firstname.lastname@example.org
Received 12 August, 2011
Revised 2 November, 2011
Accepted 14 November, 2011
Objective: AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers.
Methods and design: This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany.
Results: Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15–0.53 and hazard ratio 0.29, 95% CI 0.16–0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25–0.93 and hazard ratio 0.47, 95% CI 0.26–0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/μl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07–0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/μl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab.
Conclusion: In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.
Despite a marked decline in incidence and prevalence  and an improved prognosis in recent years [2–4], AIDS-related lymphomas (ARL) remain a significant factor of mortality and morbidity in HIV-infected patients [5–7]. Optimal treatment remains controversial, and there is conflicting data regarding the use of the monoclonal CD20 antibody rituximab. It is still not clear whether rituximab is similarly beneficial for HIV-infected patients as it is for HIV-negative patients with B-cell lymphomas (BCLs). Several phase I/II trials with different chemotherapy protocols in combination with rituximab in patients with ARL have been published [8–13]. The encouraging results seen in these trials are in contrast with the only randomized trial comparing cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with CHOP and rituximab (R-CHOP) in which the addition of rituximab did not lead to an increase in survival . Moreover, this study showed a significant increase in the frequency of severe infections in patients treated with rituximab, especially in those with low CD4 T-cell counts. This raised concerns that the use of rituximab with consecutive B-cell depletion may be harmful in HIV-infected patients with severe T-cell defects.
The aim of the present multicenter cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL after January 2005 with regard to different therapeutic approaches (e.g. use of rituximab), clinical characteristics and histopathological markers such as CD20 expression.
Patients and methods
This observational uncontrolled multicenter cohort study includes adult HIV-1-infected patients with biopsy or cytologically proven ARL diagnosed in 25 participating German centers. All patients diagnosed between 1 January 2005 and 31 December 2008 were included.
Data on HIV-infection and lymphoma characteristics, treatment and outcome were collected and patients were followed every 6 months. Survival time was calculated from the date of ARL diagnosis until death or until the last follow-up. The causes of death were classified as related or not related to ARL or to the administered chemotherapy. For each patient, we extracted the following information: demographic characteristics; HIV and AIDS history; and immunological, virological, clinical and radiological features. Information about the clinical stage according to the Ann Arbor classification as well as treatment and remission stage of ARL were also evaluated. Characteristics of ARL included histological subtype, presence of bone marrow infiltration, B-symptoms, the number of extra nodal sites involved and the international prognostic index (IPI) score . We registered antiretroviral therapy (ART) regimens at the time of lymphoma diagnosis and throughout follow-up. The chemotherapy regimens, the number of given cycles of chemotherapy and the number of administered rituximab doses were documented.
Complete remission was defined as the absence of clinical and radiological evidence of ARL. Progression-free survival (PFS) was defined as the time from initiation of chemotherapy until lymphoma progression or death as a result of any cause. Overall survival (OS) was defined as the time from lymphoma diagnosis until death of any cause.
Fisher's exact test, Mann–Whitney U-test and χ2-test were used for comparison of frequencies. A P value of less than 0.05 was considered to be statistically significant. Kaplan–Meier survivor functions and the Cox proportional hazards regression analysis were used to evaluate OS and PFS. Use of rituximab [polychemotherapy (PCT) with rituximab vs. polychemotherapy without rituximab], prior AIDS-defining illness (yes vs. no), CD4 T-cell count at ARL diagnosis (<100 vs. ≥100 cells/μl), use of ART before ARL diagnosis (yes vs. no), suppressed HIV-RNA (<50 vs. >50 copies/ml), CD20 expression of ARL (yes vs. no) and the IPI score were considered as potential predictors. Use of rituximab was defined as at least one administration of rituximab within the chemotherapeutical first-line therapy.
Approval was granted by the ethic committee of the University of Cologne, Germany and of each participating site. Written informed consent was obtained.
In total, 163 HIV-1 infected patients diagnosed with AIDS-related BCL were enrolled. Seven patients who died before initiation of chemotherapy were considered for calculation of mortality of the entire cohort, but excluded from further analysis. The remaining 156 patients presenting with diffuse large BCL (DLBCL), Burkitt's lymphoma and high-grade BCL without further histopathological classification were analyzed in greater detail (Table 1). Median age was 45 years (range 22–74), and the vast majority (92%) were male. Median CD4 T-cell count at time of ARL diagnosis was 205 cells/μl, with a broad range from 2 to 1111 cells/μl. Seventy-four out of 156 patients (47%) had a CD4 T-cell count lower than 200 cells/μl and 42 patients (27%) had a CD4 T-cell count of lower than 100 cells/μl at ARL diagnosis. One hundred and two of 156 patients had the ARL diagnosis as their initial AIDS-defining event (65%). In 35% of the patients, ARL occurred under ART, whereas 55% of the patients were ART-naive and 10% had received ART in the past but not within the last 3 months before ARL diagnosis. Solely in six patients, ART was never initiated after ARL diagnosis due to rapid progression of ARL or fatal infection within the first cycle of chemotherapy. In four patients, the date of initiation of ART was not available. The vast majority of the remaining patients started ART during the first two cycles of chemotherapy. Most patients had a DLCBL histology subtype (60%), followed by Burkitt's lymphoma (32%) and not classifiable high-grade BCL (8%). Intermediate-risk or high-risk IPI scores were frequent, as were advanced Ann Arbor stages of ARL.
Protocols based on CHOP constituted the predominant regimens [CHOP-21: n = 72; CHOP-14: n = 29; CHOEP: n = 6; EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin): n = 5] in 112 patients (72%). In 44 patients with Burkitt's lymphoma/Burkitt-like lymphomas (n = 35) or DLBCL (n = 9), the more intensive German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) protocol (ifosphamide, high-dose methotrexate and cytarabine)  was used. Rituximab was added to the CHOP-based regimen or GMALL protocol in 74 patients (47%). The median number of rituximab doses was five (range, one to eight). Fifty-seven of 74 patients (77%) received at least four administrations of rituximab.
Survival and outcome: univariate analysis
By 31 December 2008, 61 of 163 patients (37%) had died after a median follow-up of 15 months (range 0–54). Of the 156 patients receiving chemotherapy with curative intention, 54 had died (35%), whereas 95 (61%) were alive and seven (4%) were lost to follow-up. In univariate analysis, the use of rituximab was associated with prolonged OS and PFS. The hazard ratio was 0.38 (95% CI 0.22–0.68) for OS and 0.39 (95% CI 0.23–0.66) for PFS, respectively (Tables 2 and 3). Estimated 2-year OS was 49% for those patients treated without rituximab (n = 82) and 73% for those treated with rituximab (n = 74). Estimated 2-year PFS was 47% for patients treated without rituximab and 71% for those getting rituximab. Of the 156 ARL cases treated with curative intention, 128 were positive for CD20 expression (82%) and 21 were CD20-negative (13%). In seven patients, the CD20 expression status was not available (4%). OS and PFS were significantly longer in patients with CD20-positive ARL than in CD20-negative lymphomas. The hazard ratio was 0.28 (95% CI 0.15–0.53) for OS and 0.29 (95% CI 0.16–0.53) for PFS (Tables 2 and 3). Baseline characteristics like age, sex, previous AIDS-defining illness, CD4 T-cell count, ART history or IPI score did not differ significantly between patients with CD20-positive and CD20-negative cases. Of note, the proportion of Burkitt's lymphoma subtype was significantly higher in the group of CD20-positive cases (P = 0.03), and high-grade lymphomas without further histopathological classification have been predominately observed in CD20-negative cases (P = 0.01; Table 1). CD20-negative cases did not receive rituximab in addition to chemotherapy.
In the group of 128 CD20-positive ARL, the combination of chemotherapy with rituximab was associated with better OS and PFS. The hazard ratio was 0.48 (95% CI 0.25–0.93) for OS and 0.47 (95% CI 0.26–0.86) for PFS (Fig. 1, Tables 2 and 3).
This was also seen in the subgroup of patients with a severely compromised immune system, as indicated by CD4 T-cell counts of less than 100 cells/μl. In this group (n = 33), the use of rituximab (n = 16) was associated with prolonged OS (hazard ratio 0.25, 95% CI 0.07–0.90; Fig. 2) and a trend toward better PFS (hazard ratio 0.35, 95% CI 0.12–1.02). Furthermore, we did not observe an increased risk of fatal infections due to the use of rituximab in these severely immunosuppressed patients.
Some baseline characteristics differed between CD20-positive patients treated with rituximab and those treated with PCT only. In the rituximab group, the median CD4 T-cell count and the proportion of Burkitt's subtype were higher than in the PCT only group (Table 1). In contrast to other cohort studies , patients with Burkitt's lymphoma had no reduced OS in our cohort (hazard ratio 0.58, 95% CI 0.30–1.12). The PFS was even better in Burkitt's lymphoma than in DLBCL (hazard ratio 0.50, 95% CI 0.27–0.95).
Survival and outcome: multivariate analysis
We evaluated a variety of prognostic parameters for their effect on OS and PFS, including demographic factors (age, sex), lymphoma-specific factors (histology, IPI score, CD20 expression, bone marrow involvement), HIV-related factors (CD4 T-cell count, detectable HIV-RNA at lymphoma diagnosis, prior ART and prior AIDS-defining illnesses) and the use of rituximab.
In univariate analysis in the entire group of CD20-positive and CD20-negative ARL, a CD4 T-cell count more than 100 cells/μl, no ART at ARL diagnosis, CD20 expression, a low IPI score, no bone marrow involvement and the use of rituximab were predictive of better OS and/or PFS. These parameters were included into the multivariate model. We did not observe any influence of histology (Burkitt's lymphoma, DLBCL or unclassified high-grade lymphoma) on OS in our cohort.
In multivariate analysis, a low IPI score, the use of rituximab and CD20 expression were associated with a strong and consistent positive effect both on OS and on PFS (Tables 2 and 3). Hazard ratios for OS were 2.85 (95% CI 1.01–8.10), 0.43 (95% CI 0.21–0.89) and 0.31 (95% CI 0.15–0.63) for a low IPI score, the use of rituximab and CD20 expression, respectively. Hazard ratios for PFS were 4.41 (95% CI 1.46–11.71), 0.44 (95% CI 0.23–0.84) and 0.24 (95% CI 0.12–0.47), respectively (Tables 2 and 3).
To differentiate between the influence of CD20 expression and the effect of rituximab, univariate and multivariate analysis had been performed furthermore in the subgroup of CD20-positive ARL. In these patients, the effect of rituximab on OS and PFS was consistently statistically significant in all analysis. In multivariate analysis, hazard ratio for OS and PFS were 0.42 (95% CI 0.20–0.87) and 0.45 (95% CI 0.23–0.88; Tables 2 and 3). Next to the use of rituximab, a CD4 T-cell count more than 100 cells/μl was associated with a positive effect both on OS and PFS [0.40 (95% CI 0.18–0.85) and 0.48 (95% CI 0.25–0.94, respectively; Tables 2 and 3].
Causes of death
After a median follow-up of 15 months, 61 of the 163 ARL patients had died (37%). Causes of death were lymphoma (n = 36, 67%), fatal infections (n = 12, 22%) and various reasons (myocardial infarction, liver failure, suicide, unknown, n = 6, 11%). The deaths due to fatal infections were considered to be treatment-related. Among these treatment-related deaths, three patients received PCT combined with rituximab and nine patients received PCT without rituximab. The median CD4 T-cell counts at baseline in patients who died due to fatal infections did not differ between patients receiving rituximab (median 104 cells/μl) and those without rituximab (median 100 cells/μl).
Out of 54 deaths in patients with curative treatment intention, 37 deaths (69%) occurred in patients with CD4 T-cell counts less than 200 cells/μl and 19 deaths (35%) occurred in patients with CD4 T-cell counts less than 100 cells/μl. Not only the ARL-related mortality (insufficient response to PCT or relapse, 20 of 36 deaths, 55%) but also the infection-related mortality (10 of 12 fatal infections) occurred predominately in patients with CD4 T-cell counts less than 200 cells/μl (five of 12 fatal infections occurred with CD4 T-cell counts <100 cells/μl).
In our multicenter cohort of patients with ARL, CD20 expression, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections. Sixty-one out of 163 patients (37%) had died after a median follow-up of 15 months. These data are in accordance with the findings of other cohorts, demonstrating that the mortality of ARL patients remains high, even with suppressive ART and despite the increasing use of standard PCT protocols [17–20].
The majority of patients with ARL did not receive ART at the time of lymphoma diagnosis, and only 24% had a HIV-RNA of less than 50 copies/ml. Approximately half of our patients had a CD4 T-cell count lower than 200 cells/μl and 27% of the patients had a CD4 T-cell count lower than 100 cells/μl at ARL diagnosis. One hundred and two of 156 patients had the ARL diagnosis as their initial AIDS-defining event (65%). In 35 of 156 patients (22%), HIV and ARL were diagnosed concurrently (time frame <4 weeks). Thus, a relevant proportion of our patients were late presenters. Next to severe immune suppression and delayed initiation of ART, HIV viremia has been identified as a risk factor for the development of lymphomas [21,22].
After the diagnosis of ARL, immunological and virological response to ART had been shown to be important prognostic factors [23,24]. In contrast to other investigators , we did not observe an influence of antiretroviral pretreatment on survival (Table 2). In contrast to pretreated patients, ART-naive patients starting ART after ARL diagnosis may have an additional beneficial effect on the control of lymphoma. However, this effect could not be observed in our cohort.
In contrast to other cohort studies , patients with Burkitt's lymphoma had a better outcome than patients with DLBCL in our cohort, probably reflecting the frequent use of more intensive and effective approaches such as the GMALL protocol in Burkitt's lymphoma in Germany. Consistently with previous studies [17,25], we found an influence of the degree of the immunodeficiency on survival. In the multivariate analysis, a CD4 T-cell count more than 100 cells/μl was associated with better OS and PFS. Out of 54 deaths in patients with curative treatment intention, 37 deaths (69%) occurred in patients with CD4 T-cell counts less than 200 cells/μl and 19 deaths (35%) occurred in patients with CD4 T-cell counts less than 100 cells/μl.
The second factor, which was associated with better outcome, was CD20 expression of lymphomas. As shown in a previous study , patients with CD20-negative lymphomas had a poorer OS and PFS in comparison to CD20-positive cases. As the therapeutic option of using a CD20 antibody does not exist in this entity, distinct therapeutic strategies for these types of lymphomas are urgently needed.
For a long time, it was not clear whether rituximab was well tolerated and effective in HIV-infected patients with BCL. In the AIDS-Malignancies Consortium (AMC) 010 trial, 143 patients with CD20-positive ARL were randomized to CHOP or R-CHOP . The slightly better response in the R-CHOP arm was outweighed by a higher incidence of severe infections with the majority of deaths occurring in those with CD4 cell counts less than 50 cells/μl. Of note, some baseline characteristics of patients differed between the prospective randomized AMC 010 trial and our cohort study. In the AMC 010 trial, the median CD4 T-cell (133 vs. 205 cells/μl) was lower and the proportion of patients with a CD4 T-cell count less than 50 cells/μl was higher (25 vs. 18%), More patients of the AMC 010 trial have had an advanced stage disease (stage III/IV, 79 vs. 60%) and only 26% of patients have been ART-naive at ARL diagnosis (vs. 55% of patients in our cohort). These unfavorable differences in baseline parameters might be account for difference in outcome between these trials.
In contrast to AMC 010, some nonrandomized studies did not show an increased rate of fatal infections under rituximab in combination with different PCT protocols [8,11]. A recent published randomized trial compared rituximab either concurrently or sequentially with the EPOCH regimen in HIV-associated BCLs, with promising complete remission rate and no increased toxicity in both the concurrent and sequential arm . The proportion of patients with a CD4 T-cell count lower than 100 cells/μl was 31% and comparable to our cohort (26%). However, comparisons between R-EPOCH and other immunochemotherapy regimens are lacking in ARL and data about the feasibility of rituximab therapy in the setting of severe immune deficiency are limited. There are also some retrospective cohort studies [4,17,27] addressing prognostic factors of survival in ARL. In these studies, however, information about the immunophenotype, chemotherapy or the use of rituximab was not available or insufficient. In an attempt to overcome these limitations, we included not only HIV-related prognostic factors in the analysis, but also lymphoma-specific factors (histological subtype, CD20 expression, bone marrow involvement) and the application of rituximab. In contrast to the AMC 010 study, we found an improved OS and PFS in patients receiving rituximab. This was observed both in the entire group of high-grade ARL as well as in the subgroup of CD20-positive cases and remained evident even in the setting of a severe immune deficiency.
In accordance with other studies [3,8,13], we did not observe an increased risk of fatal infections due to the use of rituximab in our cohort. However, the patients who died from treatment-associated infections had lower CD4 T cells than the entire group. These findings emphasize the need for prospective trials evaluating the benefits of intensified supportive care (e.g. use of granulocyte-colony stimulating factor, early or prophylactic use of anti-infective agents).
This study has some limitations. The uncontrolled design resulted in differences in baseline characteristics between patients with or without rituximab. However, there were no differences in IPI score between patients receiving and not receiving rituximab. The median CD4 T-cell counts were higher in patients receiving rituximab, indicating a potential confounding bias arising from the treating physician's decision of whether or not to add rituximab to PCT in an individual patient. In addition, the proportion of ART-naive patients was higher in patients receiving rituximab. Although only further and larger randomized clinical trials can prove the efficacy and safety of rituximab in this setting, our study strongly indicates a positive effect.
In conclusion, in this multicenter cohort study of HIV-infected patients presenting with ARL, the use of rituximab improved OS and PFS. This effect was seen even in the setting of severe immune deficiency and without an increased risk of fatal infections. The substantial mortality rate, especially in those patients with severe immune deficiency and with lack of CD20 expression, emphasizes the need for further clinical research in ARLs.
First, the authors thank all the patients participating in our cohort for providing their data and biomaterials to the cohort. The authors are grateful for all the work and dedication of the documentation officers and of the heads of the participating sites: Axel Adam (Hamburg), Johannes Bogner (Munich), Hans-Reinhard Brodt (Frankfurt am Main), Thomas Buhk (Hamburg), Andrea Eberhardt (Munich), Stefan Fenske (Hamburg), Holger Gerigk (Hamburg), Daniel Gillor (Cologne), Ingo Greiffenburg (Krefeld), Georg Haerter (Ulm), Stefan Hansen (Hamburg), Angela Hammond (Augsburg), Christian Hoffmann (Hamburg), Heinz-August Horst (Kiel), Andreas Humpe (Kiel), Eva Jaegel-Guedes (Munich), Hans Jäger (Munich), Ulf Kloenne (Muenster), Heribert Knechten (Aachen), Gisela Kremer (Cologne), H. Lehmann (Dresden), Jan van Lunzen (Hamburg), Franz Mosthaf (Karlsruhe), Birgit Ross (Essen), Bernhard Schaaf (Lubeck), Carl Knud Schewe (Hamburg), B. Sonntag (Munich), Hans-Jürgen Stellbrink (Hamburg), Thomas Sternfeld (Munich), Albrecht Stoehr (Hamburg), Jan Thoden (Freiburg), Mathias Vierbuchen (Hamburg), Jan-Christian Wasmuth (Bonn), Lutwin Weitner (Hamburg), Timo Wolf (Frankfurt) and Kathrin Zuchold (Berlin).
C.W., G.F. and C.H. conceived and designed the study; C.W., B.J., M.H., J.S., M.S., S.E., M.M., J.V.L., T.M., J.R.B., J.C.W., G.F. and C.H. provided patients. C.W., D.G. and C.H. collected and assembled the data. C.W., H.C., G.F. and C.H. analyzed and interpreted data. All authors wrote the manuscript, had access to the primary clinical data and gave final approval of the manuscript.
Furthermore, the authors would like to thank Philipp Schommers, Cologne for administrative assistance and Hartmut Stützer, Cologne for performing the statistical analyses.
This work was funded by the BMBF (Federal Ministry of Education and Research, Germany; grant number 01 KI 0771).
Conflicts of interest
C.W. has received consulting fees from Boehringer Ingelheim, fees for speaking engagements from Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, MSD, Janssen-Cilag, Essex, Pfizer and Abbott. M.M. has received fees for speaking engagements from MSD. J.V.L. has received fees for board membership from BMS, Boehringer, Abbott, ViiV, MSD, Bionor AS and Gilead, Janssen; consulting fees from BMS, Boehringer, Abbott, ViiV, MSD, Bionor AS, Gilead and Janssen; grants from BMS, Gilead and Janssen; fees for speaking engagements from BMS, Boehringer, Abbott, ViiV, MSD, Bionor AS, Gilead, Janssen and Roche; and payments for development of educational presentations from MS, Gilead and MSD. J.R.B. has received consulting fees from Abbott, Boehringer Ingelheim, MSD, Janssen-Cilag and fees for speaking engagements from Abbott, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen-Cilag, ViiV Healthcare, MSD, Pfizer, Roche and Novartis. T.M. has received support for travel to meetings from MSD, Gilead and BMS. M.S. has received consulting fees from BMS, ViiV-Healthcare, Abbott, Janssen-Cilag and fees for speaking engagements from BMS, ViiV-Healthcare and Abbott, Janssen-Cilag. B.J. has received consulting fees from Boehringer Ingelheim and fees for speaking engagements from Janssen-Cilag. M.H. has received support for travel to meetings from Harlachinger Krebshilfe, Celgene, Janssen-Cilag, Novartis, Pfizer and Roche Pharma, consulting fees from Takeda Pharma GmbH and fees for speaking engagements from Boehringer Ingelheim, Celgene, Gilead Sciences, MSD, Novartis, Pfizer and Roche Pharma. S.E. has received consulting fees from Abbott, BMS, Boehringer, Gilead, Janssen, MSD, Roche and ViiV, support for travel to meetings from Abbott, BMS, Boehringer, Gilead, Janssen, MSD, Roche and ViiV and fees for board membership from Abbott, BMS, Boehringer, Gilead, Janssen, MSD and ViiV. G.F. has received consulting fees Abbott, Boehringer Ingelheim, MSD, Janssen-Cilag, Gilead and ViiV Healthcare and fees for speaking engagements from Abbott, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen-Cilag, ViiV Healthcare, MSD, Pfizer and Roche. C.H. has received consulting fees from Abbott, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, MSD, Roche and ViiV Healthcare, fees for board membership from Abbott, BMS, Gilead Sciences, Janssen-Cilag, MSD, Roche and ViiV Healthcare and fees for speaking engagements from Abbott, BMS, Gilead Sciences, Janssen-Cilag, MSD, Roche and ViiV Healthcare. For the remaining authors, no conflicts of interest are declared.
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AIDS-related lymphoma; HIV; multicenter cohort study; rituximab
© 2012 Lippincott Williams & Wilkins, Inc.
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