Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia, Focusing on Long Term Cytopenias Before and After the Era of Targeted Therapies

被引：3

作者：

Szasz, Robert ^{[1
]}

Telek, Bela ^{[1
]}

Illes, Arpad ^{[1
]}

机构：

[1] Univ Debrecen, Fac Med, Dept Internal Med, Div Hematol, Debrecen, Hungary

来源：

PATHOLOGY & ONCOLOGY RESEARCH | 2021年 / 27卷

关键词：

treatment; chronic lymphocytic leukemia; fludarabine; cyclophosphamide; rituximab; cytopenia; PREVIOUSLY UNTREATED PATIENTS; LOW-DOSE FLUDARABINE; 1ST-LINE TREATMENT; INITIAL THERAPY; PLUS CHLORAMBUCIL; ELDERLY-PATIENTS; CHEMOIMMUNOTHERAPY; IBRUTINIB; CLL; OBINUTUZUMAB;

D O I：

10.3389/pore.2021.1609742

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The widespread application of fludarabine, cyclophosphamide, and rituximab combination is limited due to its toxicity, particularly the prolonged cytopenias. The study aimed to compare the prolonged cytopenias depending on fitness and report real-life data on dose reduction measures and efficacy. According to our database, 120 and 14 patients were treated with FCR between 2011 and 2015 and between 2016 and 2019. Out of the first cohort, 34 patients were treated in subsequent lines. The complete and partial remission rate after first-line treatment was 79%, 16% in the first cohort and 86%, 14% in the second cohort, respectively; and 47%, 35% after non first-line treatment. Based on today's standards, only 37.5% of the patients were fit for FCR. The frequency of persistent cytopenia was 14%, and it was significantly associated with fitness (chi (2) (1) = 6.001, p = 0.014 for all patients). The small number of FCR treated patients after 2016 shows how the availability of targeted therapies, mostly ibrutinib, in later lines changed the first-line choice. Recently, it is recommended first-line for fit patients with mutated IGHV and no TP53 aberrations. With this narrow indication, a decrease in the frequency of persistent cytopenias is predicted.

引用

页数：7

共 23 条

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Cencini, Emanuele ;

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Morabito, Fortunato ;

Mura, Maria Angela ;

Soriani, Silvia ;

Peragine, Nadia ;

Tavolaro, Simona ;

Bonina, Silvia ;

Marinelli, Marilisa ;

De Propris, Maria Stefania ;

Della Starza, Irene ;

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Laman, Andrew ;

Sulecki, Mathew ;

Butchko, Allyson ;

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Lenzer, Diana ;

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Sarasquete, Maria E. ;

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Morscio, Julie ;

Martinez, Antonio ;

Alcoceba, Miguel ;

Fresquet, Vicente ;

Gonzalez-Farre, Blanca ;

Paiva, Bruno ;

Young, Ken H. ;

Robles, Eloy F. ;

Roa, Sergio ;

Celay, Jon ;

Larrayoz, Marta ;

Rossi, Davide ;

Gaidano, Gianluca ;

Montes-Moreno, Santiago ;

Piris, Miguel A. ;

Balanzategui, Ana ;

Jimenez, Cristina ;

Rodriguez, Idoia ;

Calasanz, Maria J. ;

Larrayoz, Maria J. ;

Segura, Victor ;

Garcia-Munoz, Ricardo ;

Rabasa, Maria P. ;

Yi, Shuhua ;

Li, Jianyong ;

Zhang, Mingzhi ;

Xu-Monette, Zijun Y. ;

Puig-Moron, Noemi ;

Orfao, Alberto ;

Boettcher, Sebastian ;

Hernandez-Rivas, Jesus M. ;

San Miguel, Jesus ;

Prosper, Felipe ;

Tousseyn, Thomas ;

Sagaert, Xavier ;

Gonzalez, Marcos ;

Martinez-Climent, Jose A. .

JOURNAL OF PATHOLOGY, 2018, 245 (01) :61-73

← 1 2 3 →

共 23 条

Barr, Paul ;

Robak, Tadeusz ;

Owen, Carolyn J. ;

Tedeschi, Alessandra ;

Bairey, Osnat ;

Bartlett, Nancy L. ;

Burger, Jan ;

Hillmen, Peter ;

Coutre, Steven ;

Devereux, Stephen ;

Grosicki, Sebastian ;

McCarthy, Helen ;

Li, Jianyong ;

Simpson, David ;

Offner, Fritz ;

Moreno, Carol ;

Zhou, Cathy ;

Styles, Lori ;

James, Danelle F. ;

Kipps, Thomas J. ;

Ghia, Paolo .

BLOOD, 2016, 128 (22)

[2] Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia [J].

Burger, J. A. ;

Tedeschi, A. ;

Barr, P. M. ;

Robak, T. ;

Owen, C. ;

Ghia, P. ;

Bairey, O. ;

Hillmen, P. ;

Bartlett, N. L. ;

Li, J. ;

Simpson, D. ;

Grosicki, S. ;

Devereux, S. ;

McCarthy, H. ;

Coutre, S. ;

Quach, H. ;

Gaidano, G. ;

Maslyak, Z. ;

Stevens, D. A. ;

Janssens, A. ;

Offner, F. ;

Mayer, J. ;

O'Dwyer, M. ;

Hellmann, A. ;

Schuh, A. ;

Siddiqi, T. ;

Polliack, A. ;

Tam, C. S. ;

Suri, D. ;

Cheng, M. ;

Clow, F. ;

Styles, L. ;

James, D. F. ;

Kipps, T. J. ;

Keating, Michael ;

Jen, Jie ;

Jindra, Pavel ;

Simkovic, Martin ;

Braester, Andrei ;

Ruchlemer, Rosa ;

Foa, Roberto ;

Semenzato, Gianpietro ;

Hawkins, Timothy ;

Atanasio, Carolina Moreno ;

Demirkan, Fatih ;

Kaynar, Leylagul ;

Pylypenko, Halyna ;

Fox, Christopher ;

Thirman, Michael ;

Campbell, Philip .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (25) :2425-2437

[3] Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia [J].

Byrd, J. C. ;

Brown, J. R. ;

O'Brien, S. ;

Barrientos, J. C. ;

Kay, N. E. ;

Reddy, N. M. ;

Coutre, S. ;

Tam, C. S. ;

Mulligan, S. P. ;

Jaeger, U. ;

Devereux, S. ;

Barr, P. M. ;

Furman, R. R. ;

Kipps, T. J. ;

Cymbalista, F. ;

Pocock, C. ;

Thornton, P. ;

Caligaris-Cappio, F. ;

Robak, T. ;

Delgado, J. ;

Schuster, S. J. ;

Montillo, M. ;

Schuh, A. ;

de Vos, S. ;

Gill, D. ;

Bloor, A. ;

Dearden, C. ;

Moreno, C. ;

Jones, J. J. ;

Chu, A. D. ;

Fardis, M. ;

McGreivy, J. ;

Clow, F. ;

James, D. F. ;

Hillmen, P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (03) :213-223

[4] Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia [J].

Dartigeas, Caroline ;

Van Den Neste, Eric ;

Berthou, Christian ;

Maisonneuve, Herve ;

Lepretre, Stephane ;

Dilhuydy, Marie-Sarah ;

Bene, Marie-Christine ;

Nguyen-Khac, Florence ;

Letestu, Remi ;

Cymbalista, Florence ;

De Guibert, Sophie ;

Aurran, Therese ;

Laribi, Kamel ;

Vilque, Jean-Pierre ;

Tournilhac, Olivier ;

Delmer, Alain ;

Feugier, Pierre ;

Cazin, Bruno ;

Michallet, Anne-Sophie ;

Levy, Vincent ;

Troussard, Xavier ;

Delepine, Roselyne ;

Tavernier, Elsa ;

Colombat, Philippe ;

Leblond, Veronique .

LEUKEMIA & LYMPHOMA, 2016, 57 (02) :328-334

[5] Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions [J].

Fischer, K. ;

Al-Sawaf, O. ;

Bahlo, J. ;

Fink, A. -M. ;

Tandon, M. ;

Dixon, M. ;

Robrecht, S. ;

Warburton, S. ;

Humphrey, K. ;

Samoylova, O. ;

Liberati, A. M. ;

Pinilla-Ibarz, J. ;

Opat, S. ;

Sivcheva, L. ;

Du, K. Le ;

Fogliatto, L. M. ;

Niemann, C. U. ;

Weinkove, R. ;

Robinson, S. ;

Kipps, T. J. ;

Boettcher, S. ;

Tausch, E. ;

Humerickhouse, R. ;

Eichhorst, B. ;

Wendtner, C. -M. ;

Langerak, A. W. ;

Kreuzer, K. -A. ;

Ritgen, M. ;

Goede, V. ;

Stilgenbauer, S. ;

Mobasher, M. ;

Hallek, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (23) :2225-2236

[6] Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial [J].

Fischer, Kirsten ;

Bahlo, Jasmin ;

Fink, Anna Maria ;

Goede, Valentin ;

Herling, Carmen Diana ;

Cramer, Paula ;

Langerbeins, Petra ;

von Tresckow, Julia ;

Engelke, Anja ;

Maurer, Christian ;

Kovacs, Gabor ;

Herling, Marco ;

Tausch, Eugen ;

Kreuzer, Karl-Anton ;

Eichhorst, Barbara ;

Boettcher, Sebastian ;

Seymour, John F. ;

Ghia, Paolo ;

Marlton, Paula ;

Kneba, Michael ;

Wendtner, Clemens-Martin ;

Doehner, Hartmut ;

Stilgenbauer, Stephan ;

Hallek, Michael .

BLOOD, 2016, 127 (02) :208-215

Fischer, Kirsten ;

Cramer, Paula ;

Busch, Raymonde ;

Boettcher, Sebastian ;

Bahlo, Jasmin ;

Schubert, Joeerg ;

Pflueger, Karl H. ;

Schott, Silke ;

Goede, Valentin ;

Isfort, Susanne ;

von Tresckow, Julia ;

Fink, Anna-Maria ;

Buehler, Andreas ;

Winkler, Dirk ;

Kreuzer, Karl-Anton ;

Staib, Peter ;

Ritgen, Matthias ;

Kneba, Michael ;

Doehner, Hartmut ;

Eichhorst, Barbara F. ;

Hallek, Michael ;

Stilgenbauer, Stephan ;

Wendtner, Clemens-Martin .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (26) :3209-3216

[8] Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients [J].

Foa, Robin ;

Del Giudice, Ilaria ;

Cuneo, Antonio ;

Del Poeta, Giovanni ;

Ciolli, Stefania ;

Di Raimondo, Francesco ;

Lauria, Francesco ;

Cencini, Emanuele ;

Rigolin, Gian Matteo ;

Cortelezzi, Agostino ;

Nobile, Francesco ;

Callea, Vincenzo ;

Brugiatelli, Maura ;

Massaia, Massimo ;

Molica, Stefano ;

Trentin, Livio ;

Rizzi, Rita ;

Specchia, Giorgina ;

Di Serio, Francesca ;

Orsucci, Lorella ;

Ambrosetti, Achille ;

Montillo, Marco ;

Zinzani, Pier Luigi ;

Ferrara, Felicetto ;

Morabito, Fortunato ;

Mura, Maria Angela ;

Soriani, Silvia ;

Peragine, Nadia ;

Tavolaro, Simona ;

Bonina, Silvia ;

Marinelli, Marilisa ;

De Propris, Maria Stefania ;

Della Starza, Irene ;

Piciocchi, Alfonso ;

Alietti, Alessandra ;

Runggaldier, Eva Josephine ;

Gamba, Enrica ;

Mauro, Francesca Romana ;

Chiaretti, Sabina ;

Guarini, Anna .

AMERICAN JOURNAL OF HEMATOLOGY, 2014, 89 (05) :480-486

[9] Chemoimmunotherapy With Low-Dose Fludarabine and Cyclophosphamide and High Dose Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia [J].

Foon, Kenneth A. ;

Boyiadzis, Michael ;

Land, Stephanie R. ;

Marks, Stanley ;

Raptis, Anastasios ;

Pietragallo, Louis ;

Meisner, Dennis ;

Laman, Andrew ;

Sulecki, Mathew ;

Butchko, Allyson ;

Schaefer, Patricia ;

Lenzer, Diana ;

Tarhini, Ahmad .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (04) :498-503

[10] Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia [J].

Garcia-Barchino, Maria J. ;

Sarasquete, Maria E. ;

Panizo, Carlos ;

Morscio, Julie ;

Martinez, Antonio ;

Alcoceba, Miguel ;

Fresquet, Vicente ;

Gonzalez-Farre, Blanca ;

Paiva, Bruno ;

Young, Ken H. ;

Robles, Eloy F. ;

Roa, Sergio ;

Celay, Jon ;

Larrayoz, Marta ;

Rossi, Davide ;

Gaidano, Gianluca ;

Montes-Moreno, Santiago ;

Piris, Miguel A. ;

Balanzategui, Ana ;

Jimenez, Cristina ;

Rodriguez, Idoia ;

Calasanz, Maria J. ;

Larrayoz, Maria J. ;

Segura, Victor ;

Garcia-Munoz, Ricardo ;

Rabasa, Maria P. ;

Yi, Shuhua ;

Li, Jianyong ;

Zhang, Mingzhi ;

Xu-Monette, Zijun Y. ;

Puig-Moron, Noemi ;

Orfao, Alberto ;

Boettcher, Sebastian ;

Hernandez-Rivas, Jesus M. ;

San Miguel, Jesus ;

Prosper, Felipe ;

Tousseyn, Thomas ;

Sagaert, Xavier ;

Gonzalez, Marcos ;

Martinez-Climent, Jose A. .

JOURNAL OF PATHOLOGY, 2018, 245 (01) :61-73

← 1 2 3 →