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Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma
Yoshiki Terada, Hirohisa Nakamae, Ran Aimoto, Hiroshi Kanashima, Erina Sakamoto, Mizuki Aimoto, Eri Inoue, Hideo Koh, Takahiko Nakane, Yasunobu Takeoka, Masahiko Ohsawa, Ki-Ryang Koh, Takahisa Yamane, Yoshitaka Nakao, Kensuke Ohta, Atsuko Mugitani, Hirofumi Teshima, Masayuki Hino
Journal of Experimental & Clinical Cancer Research , 2009, DOI: 10.1186/1756-9966-28-116
Abstract: We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.Aggressive lymphoma is known to be a highly chemosensitive disease. Therefore, over the past few decades, constant attempts have been made to develop various types of combination chemotherapy including first generation combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) [1]. However, particularly in patients with aggressive lymphoma in the higher International Prognostic Index (IPI) risk group, satisfactory outcomes have not been achieved, with a five-year survival of less than 50% [2].Several retrospective studies demonstrated that the relative dose intensity (RDI) of combination chemotherapy significantly influences survival in aggressive lymphoma [3-7].Moreover, rituximab, a chimeric monoclonal anti-CD20 antibody combined with CHOP chemotherapy (R-CHOP) has improved outcome in patients with diffuse large B-cell lymphoma (DLBL) [8,9]. Rituximab has direct, complement-dependent and antibody-dependent cellular cytotoxicity against B-cells. The drug also sensitizes B-lymphoma cells to chemotherapy [10]. Therefore, a combined approach with rituximab plus CHOP could conceivably modify the effects of RDI. However, there is no evidence that even in combination chemotherapy with rituximab that higher RDI improves the outcome for aggressive B-cell type lymphoma. He
Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)
Seok Kim, Chul Choi, Yeung-Chul Mun, Sung Oh, Hye Kang, Soon Lee, Jong Won, Min Kim, Jung Kwon, Jin Kim, Jae-Yong Kwak, Jung Kwon, In Hwang, Hyo Kim, Jae Lee, Sukjoong Oh, Keon Park, Cheolwon Suh, Won Kim
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-321
Abstract: We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might
Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study
Ho-Young Yhim, Hye Kang, Yoon Choi, Seok Kim, Won Kim, Yee Chae, Jin Kim, Chul Choi, Sung Oh, Hyeon Eom, Jeong-A Kim, Jae Lee, Jong-Ho Won, Hyeok Shim, Je-Jung Lee, Hwa Sung, Hyo Kim, Dae Lee, Cheolwon Suh, Jae-Yong Kwak
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-321
Abstract: We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009.Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0.001).Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.Approximately one-third of non-Hodgkin lymphoma (NHL) arises primarily from sites other than lymph nodes; for this reason, they are usually named as primary extranodal lymphoma [1]. The definition of primary ext
Therapy Outcome of a T-Cell-Rich-B-Cell Lymphoma (TCRBCL) Patient with Rituximab-CHOP in Ibadan, Nigeria: a Case Report.  [cached]
John Ayodele Olaniyi
Mediterranean Journal of Hematology and Infectious Diseases , 2011, DOI: 10.4084/mjhid.2011.
Abstract: T-cell-rich B-cell lymphoma (TCRBCL) is considered a rare variant of aggressive B cell lymphoma characterized by few neoplastic B cells and a large reactive infiltrate with striking similarities to nodular lymphocyte predominant Hodgkin’s lymphoma. A case of a 46 year old man referred with a 5 months history of generalized lymphadenopathy, weight loss, low grade pyrexia and two separately reported lymph node histology consistent with TCRBCL is described. The clinical course was indeed aggressive because in spite of initial treatment with four cycles of CHOP combination chemotherapy, followed by Rituximab+CHOP(x 6 cycles), signs of tumor re-growth/infiltration were frequently observed. Also recurrent infection was frequent, troublesome and eventually became overwhelming resulting to the loss of the patient. This case, being the first case of TCRBCL diagnosed immunohistochemically and managed at this centre with R-CHOP, is presented to highlight the dilemma in making diagnosis (which required meticulous immunohistochemistry), clinical challenges faced and rituximab therapy outcome especially in resource poor country. It will also serve to increase our index of suspicion and the need reinforce immunohistochemistry in the diagnosis of lymphoma. Keywords:- T-cell-Rich B-cell Lymphoma, Immunohistochemistry, Rituximab, Recurrent infection
R-CHOP vs. CHOP: A Cost-Effectiveness Analysis on Aggressive Non-Hodgkin's Lymphoma (NHL)
Anca LUPU,Paul RADU,Bogdan PAN?,Cristina KALFAS
Management in Health , 2009,
Abstract: The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) is the standard treatment for younger and elderly patients with diffuse large-B-cell lymphoma, but it induces complete responses in only 40 to 50 percent of elderly patients. The benefit of adding Rituximab (R) – a chimeric anti-CD20 IgG1 monoclonal antibody, to CHOP was observed among patients with relatively low risk disease or high risk disease. In comparative studies of CHOP and R-CHOP, the rate of complete response was significantly higher in the group that received R-CHOP than in the group that received CHOP alone. In several EU countries there are cost-effectiveness studies regarding the treatment of aggressive NHL with CHOP vs. R-CHOP, but in Romania there is no such a study done.The authors used a cost-effectiveness model where they compared the costs of both type of treatments and the benefits expressed in gained years of life, in order to have the Romanian perspective for the economic evaluation of treatment of aggressive NHL with CHOP vs. R-CHOP. The Romanian cost-effectiveness analysis is based on a model developed by Best et al. which calculates the cost-effectiveness ratio of R-CHOP vs. CHOP over time horizon of 10 years for patients with diffuse large B-cell lymphoma DLCL. The analysis was done based on local Romanian costs and the clinical benefits from the GELA study. Rituximab administered together with CHOP gives patients an increased chance of cure, a significantly superior survival and represents a cost-effective therapy compared to standard treatment with CHOP. When costs and survival benefits are considered over 10 years, the additional cost per patient on R-CHOP is 12,929 Euro. Over a 10 years time frame, the estimated survival benefit of R-CHOP compared to standard CHOP treatment alone in this group of patients is on average 0.60 extra years of life gained per patient. The estimated additional cost per extra year of life gained for the combination therapy is 21,549 Euro. Using the same cost-effectiveness model we observed that using R-CHOP vs. CHOP we obtained in Romania the lowest cost per additional year of life gained compared with France or United Kingdom.
Rituximab maintenance in follicular lymphoma patients  [cached]
Luca Arcaini,Michele Merli
World Journal of Clinical Oncology , 2011, DOI: 10.5306/wjco.v2.i7.281
Abstract: Rituximab maintenance (RM) therapy following successful induction has recently emerged as a highly effective treatment for follicular lymphoma (FL). Randomized trials analyzing the impact of RM compared to observation alone have demonstrated a significantly better outcome in terms of progression-free survival (but not overall survival) in patients (pts) who received as first-line treatment single-agent rituximab, standard chemotherapy (CVP) and recently also immunochemotherapy (R-CHOP, R-CVP or R-FND), as shown by preliminary results of the PRIMA trial. Also in the setting of relapsed disease, RM has shown significant benefit either after chemotherapy or immunochemotherapy. RM has been generally well tolerated, and treated pts developed only mild toxicity, mainly a small increased rate of neutropenia, hypogammaglobulinaemia and self-limiting upper-respiratory tract infections. Moreover, no cumulative or unexpected toxicities were observed and quality of life was not affected. These data have established RM therapy as an important part of multi-modal therapeutic strategies in patients affected by FL.
Rituximab in the treatment of non-Hodgkin’s lymphoma
Beate Hauptrock,Georg Hess
Biologics: Targets and Therapy , 2008,
Abstract: Beate Hauptrock, Georg HessHematology/Oncology, Johannes Gutenberg-University, Mainz, GermanyAbstract: Besides traditional cytostatic drugs the introduction of monoclonal antibodies has substantially influenced current treatment concepts of non-Hodgkin’s lymphoma (NHL). Rituximab, a monoclonal anti-CD20 chimeric antibody, now has been widely evaluated in the various B-cell lymphatic neoplasms. Large phase III studies helped to prove the value of this drug in follicular lymphoma as part of induction or relapse treatment as well as maintenance treatment. The addition of rituximab to the well established CHOP regimens has increased achievable cure rates in diffuse large cell lymphoma, and this combination is now accepted worldwide as standard of care. Although conflicting results are available, rituximab is widely used for the treatment of mantle cell lymphoma. For the less frequent lymphoma entities phase 2 studies show a considerable efficiency for most of these B-NHL variants. Current research focuses on combined chemoimmunotherapy approaches, optimization of dosing regimens, and combination with novel agents.Keywords: non-Hodgkin’s lymphoma, rituximab, monoclonal-antibody, targeted therapy
Primary Renal Lymphoma: Long-Term Results of Two Patients Treated with a Chemotherapy + Rituximab Protocol
F. Vázquez-Alonso,I. Puche-Sanz,C. Sánchez-Ramos,J. Flores-Martín,J. Vicente-Prados,J. M. Cózar-Olmo
Case Reports in Oncological Medicine , 2012, DOI: 10.1155/2012/726424
Abstract: Primary renal lymphoma (PRL) is a rare disease of which the etiology and pathogenesis remain controversial, and there is currently no standard treatment for it. We present the results of a long-term followup of two patients who were diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine, prednisolone and rituximab (CHOP
Rituximab induced hypoglycemia in non-Hodgkin's lymphoma
Badrudeen M Hussain, N Geetha, V Lali, Manoj Pandey
World Journal of Surgical Oncology , 2006, DOI: 10.1186/1477-7819-4-89
Abstract: A 50 year old female presented with a left tonsillar non Hodgkin's lymphoma and was started on R-CHOP chemotherapy. Twenty four hours after the first rituximab infusion, she developed hypoglycemia which was managed by IV glucose infusion.Hypoglycemia following rituximab administration is rare. Possibilities of hypoglycemia should be kept in mind in patients developing symptoms like fatigue, restlessness, and sweating while on rituximab therapy.Hypoglycemia is a rare complication of rituximab treatment. The exact cause of this phenomenon is not known. We report here a case of non-Hodgkin's lymphoma developin hypoglycemia on being treated with R-CHOP chemotherapyA 50-year-old female presented in January 2004 with a 4 cm left tonsillar mass. Her general and systemic examinations were unremarkable. There was no lymphadenopathy or hepato-splenomegaly. Her hemoglobin was 12.5 gm/dl, white blood cell (WBC) count was 7700/mm3, erythrocyte sedimentation rate (ESR) was 50 mm/hour and random blood sugar (RBS) was 96 mg/dl. Renal and liver function tests were normal. VDRL, HIV and HBsAg were non-reactive. Chest X-ray, ultrasound scan of the abdomen, upper gastro-intestinal endoscopy, peripheral blood smear and bone marrow biopsy were normal. There was no past history of diabetes mellitus, hypo or hyperglycemic episodes. Biopsy and histopathological examination of the tonsillar mass was consistent with Non Hodgkin's lymphoma-diffuse large B cell type. Immunohistochemistry showed the tumor cells to be CD20 positive. She was treated using R-CHOP (rituximab 375 mg/m2 + cyclophosphamide 750 mg/m2 + doxorubicin 50 mg/m2 + vincristine 1.4 mg/m2 + prednisolone 100 mg orally) chemotherapy on a three weekly schedule after obtaining informed consent. About 24 hours following rituximab, she developed hypoglycemic symptoms like fatigue, restlessness, sweating and drowsiness. There was no other rituximab infusion related toxicities. Her RBS at that time was 39 mg/dl. Her symptoms subsided fo
B cell non-Hodgkin's lymphoma: rituximab safety experience
Ann Mohrbacher
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1739
Abstract: The US Food and Drug Administration (FDA) approved the chimeric anti-CD20 monoclonal antibody rituximab in 1997 as a single-agent treatment for relapsed or refractory, low grade or follicular CD20+, B cell non-Hodgkin's lymphoma (NHL). In as many as 85% patients, NHL is of B cell origin, and a majority has high affinity expression for CD20. For that reason, rituximab is now widely used in hematologic oncology.Almost half a million patients have been treated with rituximab, either alone or in combination, from phase II and III of development through postmarketing approval. Although not formally approved for use in combination protocols by the FDA, rituximab is now included in a standard-of-care, in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, for treatment of aggressive lymphomas of B cell origin.In the original clinical studies, patients received four weekly doses of 375 mg/m2; this dosage schedule increased to eight weekly infusions of 375 mg/m2 in subsequent trials. The choice of cumulative dosage was somewhat arbitrarily based on biologic factors. Doctors frequently give extended courses of rituximab (four to eight courses instead of the standard single 4-week course) to those patients who have not reached dose limiting toxicity.Overall, rituximab has exhibited very strong and consistent efficacy alone and in combination with virtually all of the chemotherapeutic agents used to treat B cell lymphomas. This has resulted in a very large safety database, permitting accurate assessment of the nature of the specific side effects and risks involved in using this drug.A substantial and growing body of data illustrates the safety of rituximab when used as first-line treatment and maintenance therapy for NHL. Although responses in a rheumatoid arthritis (RA) population are different from those in NHL patients, knowledge gained in the oncology setting may be of significant relevance to treatment of RA patients.McLaughlin
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