Clinical Effect of CD25 on the Prognosis of Diffuse Large B Cell Lymphoma with Secondary Central Nervous System Relapse
In the present study, we investigated the effects of immunophenotyping on prognosis of diffuse large B cell lymphoma (DLBCL) with central nervous system (CNS) relapse treated with rituximab-CHOP (R-CHOP). CNS relapse occurred in 9.5% of DLBCL patients. At the diagnosis of DLBCL, CD25 was detected in 14.3% of cases. CD25 positivity correlated with an advanced stage, higher R-IPI, higher CNS-IPI, the presence of B symptoms, the presence of extranodal involvement >1, and bone involvement. Moreover CNS relapse was more frequently observed in patients with CD25+ than in those with CD25-. The univariate analysis showed that an advanced stage, high-risk R-IPI, high-risk CNS-IPI, bone involvement, and CD25+ were associated with shorter overall survival (OS). The multivariate analysis confirmed that CD25+ and high-risk CNS-IPI were independent adverse prognostic factors for shorter OS. A Kaplan-Meier analysis revealed the potential of CD25+ as a prognostic factor in patients with CNS relapse and that it correlated with shorter survival. The present results showed that the expression of CD25 in DLBCL patients with CNS relapse was associated with the patient prognosis independent other prognostic factors. The establishment of a treatment strategy for CNS relapse patients with CD25+ DLBCL cells is needed to improve poor outcomes.
KeywordsDiffuse large B cell lymphoma Central nervous system relapse CD25 Rituximab
Compliance with Ethical Standards
Conflict of Interest
Satoko Oka declares that she has no conflicts of interest in the present study.
Kazuo Ono declares that he has no conflicts of interest in the present study.
Masaharu Nohgawa declares that he has no conflicts of interest in the present study.
This article does not contain any studies with human participants performed by any of the authors.
These patients provided their written informed consent to receive each regimens, and treatments were administered according to the principles of the Declaration of Helsinki and this study was approved by the institutional ethics committee.
- 1.Boehme V, Zeynalova S, Kloess M, Loeffler M, Kaiser U, Pfreundschuh M, Schmitz N, German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) (2007) Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German high-grade non-Hodgkin's lymphoma study group (DSHNHL). Ann Oncol 18:149–157CrossRefGoogle Scholar
- 2.Tomita N, Yokoyama M, Yamamoto W, Watanabe R, Shimazu Y, Masaki Y, Tsunoda S, Hashimoto C, Murayama K, Yano T, Okamoto R, Kikuchi A, Tamura K, Sato K, Sunami K, Shibayama H, Takimoto R, Ohshima R, Hatta Y, Moriuchi Y, Kinoshita T, Yamamoto M, Numata A, Ishigatsubo Y, Takeuchi K (2012) Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era. Cancer Sci 103:245–251CrossRefGoogle Scholar
- 6.Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ (2016) CNS international prognostic index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 34:3150–3156CrossRefGoogle Scholar
- 9.Alinari L, Gru A, Quinion C, Huang Y, Lozanski A, Lozanski G, Poston J, Venkataraman G, Oak E, Kreisel F, Park SI, Matthews S, Abramson JS, Iris Lim H, Martin P, Cohen JB, Evens A, al-Mansour Z, Singavi A, Fenske TS, Blum KA (2016) De novo CD5+ diffuse large B-cell lymphoma: adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort. Am J Hematol 91:395–399CrossRefGoogle Scholar
- 15.Hashimoto Y, Yokohama A, Saitoh A, Nakahashi H, Toyama K, Mitsui T, Koiso H, Saitoh T, Handa H, Uchiumi H, Jinbo T, Murayama K, Matsumoto M, Sawamura M, Karasawa M, Murakami H, Hirato J, Nojima Y, Kojima M, Tsukamoto N (2013) Prognostic importance of the soluble form of IL-2 receptorα (sIL-2Rα) and its relationship with surface expression of IL-2Rα (CD25) of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab: a retrospective analysis of 338 cases. J Clin Exp Hematop 53(3):197–205CrossRefGoogle Scholar
- 24.Petrich AM, Gandhi M, Jovanovic B, Castillo JJ, Rajguru S, Yang DT, Shah KA, Whyman JD, Lansigan F, Hernandez-Ilizaliturri FJ, Lee LX, Barta SK, Melinamani S, Karmali R, Adeimy C, Smith S, Dalal N, Nabhan C, Peace D, Vose J, Evens AM, Shah N, Fenske TS, Zelenetz AD, Landsburg DJ, Howlett C, Mato A, Jaglal M, Chavez JC, Tsai JP, Reddy N, Li S, Handler C, Flowers CR, Cohen JB, Blum KA, Song K, Sun HL, Press O, Cassaday R, Jaso J, Medeiros LJ, Sohani AR, Abramson JS (2014) Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood. 124:2354–2361CrossRefGoogle Scholar
- 25.Feugier P, Virion JM, Tilly H, Haioun C, Marit G, Macro M, Bordessoule D, Recher C, Blanc M, Molina T, Lederlin P, Coiffier B (2004) Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol 15:129–133CrossRefGoogle Scholar
- 29.Zucca E, Conconi A, Mughal TI, Sarris AH, Seymour JF, Vitolo U, Klasa R, Ozsahin M, Mead GM, Gianni MA, Cortelazzo S, Ferreri AJ, Ambrosetti A, Martelli M, Thiéblemont C, Moreno HG, Pinotti G, Martinelli G, Mozzana R, Grisanti S, Provencio M, Balzarotti M, Laveder F, Oltean G, Callea V, Roy P, Cavalli F, Gospodarowicz MK, International Extranodal Lymphoma Study Group (2003) Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the international Extranodal lymphoma study group. J Clin Oncol 21:20–27CrossRefGoogle Scholar
- 31.Kumar A, Vanderplas A, LaCasce AS, Rodriguez MA, Crosby AL, Lepisto E, Czuczman MS, Nademanee A, Niland J, Gordon LI, Millenson M, Zelenetz AD, Friedberg JW, Abel GA (2012) Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: findings from a large national database. Cancer. 118:2944–2951CrossRefGoogle Scholar
- 33.Grommes C, Tang SS, Wolfe J, Kaley TJ, Daras M, Pentsova EI, Piotrowski AF, Stone J, Lin A, Nolan CP, Manne M, Codega P, Campos C, Viale A, Thomas AA, Berger MF, Hatzoglou V, Reiner AS, Panageas KS, DeAngelis L, Mellinghoff IK (2019) Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma. Blood. 133:436–445CrossRefGoogle Scholar
- 34.Rubenstein JL, Geng H, Fraser EJ, Formaker P, Chen L, Sharma J, Killea P, Choi K, Ventura J, Kurhanewicz J, Lowell C, Hwang J, Treseler P, Sneed PK, Li J, Wang X, Chen N, Gangoiti J, Munster PN, Damato B (2018) Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv 2:1595–1607CrossRefGoogle Scholar