Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. Materials and Methods We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Results Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. Conclusion NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.
Abstract
Purpose Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. Materials and Methods We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Results Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. Conclusion NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.
참고문헌 (24)
- 허주령, "Epidemiologic overview of malignant lymphoma", Blood Research, 47(2), pp.92~104 (2012), 대한혈액학회[DOI]
- Fisher RI, "Comparison of a standard regimen(CHOP)with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma", N Engl J Med, 328, pp.1002~1006 (1993)
- Intragumtornchai T, "A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma", Leuk Lymphoma, 37, pp.351~360 (2000)
- Klastersky J, "The Multinational Association for Supportive Care in Cancer risk index : a multinational scoring system for identifying low-risk febrile neutropenic cancer patients", J Clin Oncol, 18, pp.3038~3051 (2000)
- de Souza Viana L, "Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients", Support Care Cancer, 16, pp.841~846 (2008)
- Pettengell R, "Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma : data from the INC-EU Prospective Observational European Neutropenia Study", Br J Haematol, 144, pp.677~685 (2009)
- Pettengell R, "Impact of febrile neutropenia on R-CHOP chemotherapy delivery and hospitalizations among patients with diffuse large B-cell lymphoma", Support Care Cancer, 20, pp.647~652 (2012)
- Lanini S, "Risk of infection in patients with lymphoma receiving rituximab : systematic review and meta-analysis", BMC Med, 9, pp.36~ (2011)
- Chen WL, "Impact of interstitial pneumonia on the survival and risk factors analysis of patients with hematological malignancy", Biomed Res Int, 2013, pp.185362~ (2013)
- Katsuya H, "Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma", Leuk Lymphoma, 50, pp.1818~1823 (2009)
- Kamel S, "High incidence of Pneumocystis jirovecii pneumonia in patients receiving biweekly rituximab and cyclophosphamide, adriamycin, vincristine, and prednisone", Leuk Lymphoma, 51, pp.797~801 (2010)
- Kolstad A, "Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOEP-14regimen", Haematologica, 92, pp.139~140 (2007)
- Lyman GH, "Risk and timing of hospitalization for febrile neutropenia in patients receiving CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma", Cancer, 98, pp.2402~2409 (2003)
- Lyman GH, "Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy", Cancer, 117, pp.1917~1927 (2011)
- Kim T, "Point prevalence of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma according to the number of cycles of R-CHOP chemotherapy", Ann Hematol, 92, pp.231~238 (2013)
- Cooper N, "The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseases", Br J Haematol, 149, pp.3~13 (2010)
- Edwards JC, "B cell depletion therapy in rheumatic disease", Best Pract Res Clin Rheumatol, 20, pp.915~928 (2006)
- van der Kolk LE, "Rituximab treatment results in impaired secondary humoral immune responsiveness", Blood, 100, pp.2257~2259 (2002)
- Stasi R, "Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab", Blood, 112, pp.1147~1150 (2008)
- Bouaziz JD, "Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice", Proc Natl Acad Sci U S A, 104, pp.20878~20883 (2007)
- Kurokawa T, "Immune reconstitution of B-cell lymphoma patients receiving CHOP-based chemotherapy containing rituximab", Hematol Oncol, 29, pp.5~9 (2011)
- Kaplan LD, "Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma : AIDS-Malignancies Consortium Trial 010", Blood, 106, pp.1538~1543 (2005)
- Wagner SA, "Rituximab-induced interstitial lung disease", Am J Hematol, 82, pp.916~919 (2007)
- Ennishi D, "Increased incidence of interstitial pneumonia by CHOP combined with rituximab", Int J Hematol, 87, pp.393~397 (2008)