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Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy

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Abstract

Risk stratification of patients with relapsed and refractory follicular lymphoma (FL) remains challenging. Recently, much attention has been paid to the impact of early progression of disease within 2 years of diagnosis (early POD) on subsequent survival. The aim of this study was to clarify the clinical features and prognostic factors of patients with FL who experienced early POD. Data were available for 94 patients diagnosed with FL (clinical stage II–IV) who had received immunochemotherapy. Early POD was seen in 20 % of these patients. The Cox proportional hazards model showed worse overall survival (OS) in the patients with early POD compared with those without early POD (5-year OS rates 48 % vs. 96 %, P < 0.0001). In multivariate analysis, early POD (P = 0.003) and poor performance status (P = 0.006) remained a significant factor for subsequent OS. In Follicular Lymphoma International Prognostic Index (FLIPI)- and Follicular Lymphoma International Prognostic Index-2 (FLIPI2)-adjusted Cox regression analysis, early POD was associated with markedly reduced OS with a hazard ratio of 11.2 [95 % confidence interval (CI) 3.13–40.3, P < 0.001] and 13.5 (95 % CI 3.22–56.3, P < 0.003), respectively. Among patients who had early POD, high levels of serum lactate dehydrogenase (LDH) both at the time of initial diagnosis and first progression could be associated with worse survival (2-year OS rates 33 vs. 92 %, P < 0.0001). Evaluation of LDH levels at the time of initial diagnosis and first progression may be important to define patients who were associated with worse prognosis. Risk stratification of patients with early POD could lead to improved clinical outcomes for FL patients. Further research is needed to investigate its value for decision making.

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Abbreviations

LDH:

Lactate dehydrogenase

Early POD:

Progression of disease within 2 years after initial diagnosis

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Acknowledgments

The authors would like to thank all the doctors and nurses for their excellent patient care. We would also like to thank Yasutaka Okada, Mako Hagino, and the clinical research staff for their technical assistance and Yuka Owaki for her excellent secretarial assistance. This work was supported in part by the National Cancer Center Research and Development Fund (26-A-4).

Author contributions

S.M. collected and interpreted the data and contributed to the discussion; H.K. designed the study, collected, analyzed and interpreted the data, and wrote the manuscript; Y.H. collected the data and contributed to the discussion; H.Y., T.S., and H.T. contributed to the discussion; Y.Y. and S.N. were responsible for pathological discussion and interpreted the data; and K.Y. and T.K. supervised the research.

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Correspondence to Tomohiro Kinoshita.

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Compliance with ethical standards

Approval for this study was obtained from the Institutional Review Board at Aichi Cancer Center. This study was conducted in accordance with the Declaration of Helsinki.

Conflict of interests

T.K. has received research funding from Zenyaku Kogyo, Chugai, Ono, and Takeda. K.Y. has received funding from ARIAD, AbbVie, and Pfizer. The other authors did not receive financial compensation for authoring the manuscript.

Additional information

Satsuki Murakami and Harumi Kato equally contributed to this study.

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Murakami, S., Kato, H., Higuchi, Y. et al. Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy. Ann Hematol 95, 1259–1269 (2016). https://doi.org/10.1007/s00277-016-2690-2

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  • DOI: https://doi.org/10.1007/s00277-016-2690-2

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