Initial therapy of chronic lymphocytic leukemia

Seminars in Oncology

Volumn 43, Issue 2, 2016, Pages 241-250

  Eichhorst, Barbara ^a   Cramer, Paula ^a   Hallek, Michael ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

Author keywords

Chemoimmunotherapy; Choice of therapy; Chronic lymphocytic leukemia; Kinase inhibitors

Indexed keywords

ALEMTUZUMAB; BENDAMUSTINE; CHLORAMBUCIL; CLADRIBINE; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB; IDELALISIB; LENALIDOMIDE; OBINUTUZUMAB; OFATUMUMAB; PENTOSTATIN; RITUXIMAB; ANTINEOPLASTIC AGENT;

ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CHRONIC LYMPHATIC LEUKEMIA; HIGH RISK PATIENT; HUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POST TREATMENT SURVIVAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); CLINICAL DECISION MAKING; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MOLECULARLY TARGETED THERAPY; PATIENT SELECTION; TREATMENT OUTCOME;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL DECISION-MAKING; HUMANS; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MOLECULAR TARGETED THERAPY; PATIENT SELECTION; TREATMENT OUTCOME;

EID: 84961223886     PISSN: 00937754     EISSN: 15328708     Source Type: Journal    
DOI: 10.1053/j.seminoncol.2016.02.005     Document Type: Review

References (100)

1. S.J. Altman, A. Haut, G.E. Cartwright, and M.M. Wintrobe Early experience with p-(N, N-di-2-chloroethyl)-aminophenylbutyric acid (CB 1348), a new chemotherapeutic agent effective in the treatment of chronic lymphocytic leukemia Cancer 9 1956 512 517
2. T. Han, E.Z. Ezdinli, K. Shimaoka, and D.V. Desai Chlorambucil vs. combined chlorambucil-corticosteroid therapy in chronic lymphocytic leukemia Cancer 31 1973 502 508
3. W.H. Knospe, V. Loeb Jr, and C.M. Huguley Jr Proceedings: Bi-weekly chlorambucil treatment of chronic lymphocytic leukemia Cancer 33 1974 555 562
4. M.M. Hansen, E. Andersen, B.E. Christensen, and et al. CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): Preliminary results of a randomized multicenter study Nouv Rev Fr Hematol 30 1988 433 436
5. E. Montserrat, A. Alcala, R. Parody, and et al. Treatment of chronic lymphocytic leukemia in advanced stages. A randomized trial comparing chlorambucil plus prednisone versus cyclophosphamide, vincristine, and prednisone Cancer 56 1985 2369 2375
6. B. Raphael, J.W. Andersen, R. Silber, and et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: Long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial J Clin Oncol 9 1991 770 776
7. M.J. Keating, H. Kantarjian, S. O'Brien, and et al. Fludarabine: A new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia J Clin Oncol 9 1991 44 49
8. M.J. Keating, S. O'Brien, H. Kantarjian, and et al. Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent Blood 81 1993 2878 2884
9. Johnson S FrenchCooperativeGrouponCLL, A.G. Smith, and et al. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. The French Cooperative Group on CLL Lancet 347 1996 1432 1438
10. T. Robak, J.Z. Blonski, M. Kasznicki, and et al. Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: Report of a prospective, randomized, multicenter trial Blood 96 2000 2723 2729
11. K.R. Rai, B.L. Peterson, F.R. Appelbaum, and et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia N Engl J Med 343 2000 1750 1757
12. B.F. Eichhorst, R. Busch, G. Hopfinger, and et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia Blood 107 2006 885 891
13. I.W. Flinn, D.S. Neuberg, M.R. Grever, and et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997 J Clin Oncol 25 2007 793 798
14. D. Catovsky, S. Richards, E. Matutes, and et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): A randomised controlled trial Lancet 370 2007 230 239
15. T. Robak, J.Z. Blonski, J. Gora-Tybor, and et al. Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: Report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2) Blood 108 2006 473 479
16. G. Dighiero, K. Maloum, B. Desablens, and et al. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia N Engl J Med 338 1998 1506 1514
17. E. Montserrat, N. Villamor, A. Urbano-Ispizua, and et al. Treatment of early stage-B chronic lymphocytic leukemia with alpha-2b interferon after chlorambucil reduction of the tumoral mass Ann Hematol 63 1991 15 19
18. M. Hallek, B.D. Cheson, D. Catovsky, and et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines Blood 111 2008 5446 5456
19. Howlader NNA, Krapcho M, Garshell J, (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD. http://seercancergov/csr/1975-2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014 2014.
20. B.S. Linn, M.W. Linn, and L. Gurel Cumulative illness rating scale J Am Geriatr Soc 16 1968 622 626
21. M.D. Miller, C.F. Paradis, P.R. Houck, and et al. Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale Psychiatry Res 41 1992 237 248
22. M. Charlson, T.P. Szatrowski, J. Peterson, and J. Gold Validation of a combined comorbidity index J Clin Epidemiol 47 1994 1245 1251
23. R. Yancik, M.N. Wesley, L.A. Ries, and et al. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: A population-based study Cancer 82 1998 2123 2134
24. M.E. Hamaker, J.M. Jonker, S.E. de Rooij, A.G. Vos, C.H. Smorenburg, and B.C. van Munster Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: A systematic review Lancet Oncol 13 2012 e437 e444
25. M.E. Hamaker, M.C. Prins, and R. Stauder The relevance of a geriatric assessment for elderly patients with a haematological malignancy - A systematic review Leuk Res 38 2014 275 283
26. M. Extermann, J. Overcash, G.H. Lyman, J. Parr, and L. Balducci Comorbidity and functional status are independent in older cancer patients J Clin Oncol 16 1998 1582 1587
27. M. Extermann Measurement and impact of comorbidity in older cancer patients Crit Rev Oncol Hematol 35 2000 181 200
28. L. Balducci, and M. Extermann Management of cancer in the older person: A practical approach Oncologist 5 2000 224 237
29. H. Döhner, S. Stilgenbauer, A. Benner, and et al. Genomic aberrations and survival in chronic lymphocytic leukemia N Engl J Med 343 2000 1910 1916
30. D. Rossi, M. Cerri, C. Deambrogi, and et al. The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: Implications for overall survival and chemorefractoriness Clin Cancer Res 15 2009 995 1004
31. T. Zenz, B. Eichhorst, R. Busch, and et al. TP53 mutation and survival in chronic lymphocytic leukemia J Clin Oncol 28 2010 4473 4479
32. S. Pospisilova, D. Gonzalez, J. Malcikova, and et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia Leukemia 26 2012 1458 1461
33. S. Stilgenbauer, A. Schnaiter, P. Paschka, and et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: Results from the CLL8 trial Blood 123 2014 3247 3254
34. S. Pospisilova, D. Gonzalez, J. Malcikova, and et al. ERIC recommendations on TP53 mutation analysis in Chronic Lymphocytic Leukemia Leukemia 26 2012 1458 1461
35. L. Wang, M.S. Lawrence, Y. Wan, and et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia N Engl J Med 365 2011 2497 2506
36. D.A. Landau, S.L. Carter, P. Stojanov, and et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia Cell 152 2013 714 726
37. P. Baliakas, A. Hadzidimitriou, L.A. Sutton, and et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia Leukemia 29 2014 329 336
38. N. Di Gaetano, Y. Xiao, E. Erba, and et al. Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone British journal of haematology 114 2001 800 809
39. H. Schulz, S.K. Klein, U. Rehwald, and et al. Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia Blood 100 2002 3115 3120
40. J.C. Byrd, B.L. Peterson, V.A. Morrison, and et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: Results from Cancer and Leukemia Group B 9712 (CALGB 9712) Blood 101 2003 6 14
41. J.C. Byrd, K. Rai, B.L. Peterson, and et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: An updated retrospective comparative analysis of CALGB 9712 and CALGB 9011 Blood 105 2005 49 53
42. J.A. Woyach, A.S. Ruppert, N.A. Heerema, and et al. Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: Long-term follow-up of CALGB study 9712 J Clin Oncol 29 2011 1349 1355
43. M.J. Keating, S. O'Brien, M. Albitar, and et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia J Clin Oncol 23 2005 4079 4088
44. C.S. Tam, S. O'Brien, W. Wierda, and et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia Blood 112 2008 975 980
45. M. Hallek, K. Fischer, G. Fingerle-Rowson, and et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia: A randomised, open-label, phase III trial Lancet 376 2010 1164 1174
46. S. Bottcher, M. Ritgen, K. Fischer, and et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: A multivariate analysis from the randomized GCLLSG CLL8 trial J Clin Oncol 30 2012 980 988
47. K Fischer, J Bahlo, and AM Fink Extended follow up of the CLL8 protocol, a randomized phase-III trial of the German CLL Study Group (GCLLSG) comparing fludarabine and cyclophosphamide (FC) to FC plus rituximab (FCR) for previously untreated patients with chronic lymphocytic leukemia (CLL): Results on survival, progression-free survival, delayed neutropenias and secondary malignancies confirm superiority of the FCR regimen Blood 127 2016 208 215
48. F. Bosch, A. Ferrer, N. Villamor, and et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: High response rate and disease eradication Clin Cancer Res 14 2008 155 161
49. J.R. Brown, J. Abramson, E. Hochberg, and et al. A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL Leukemia 24 2010 1972 1975
50. A. Egle, M. Steurer, F. Gassner, and et al. Lenalidomide/rituximab maintenance after induction with fludarabine/rituximab in combination with escalating doses of lenalidomide in previously untreated chronic lymphocytic leukemia (CLL): The Revlirit CLL5 AGMT phase I/II study, final results Blood 122 2013
51. A.R. Mato, K.A. Foon, T. Feldman, and et al. Reduced-dose fludarabine, cyclophosphamide and rituximab (FCR-Lite) plus lenalidomide, followed by lenalidomide consolidation/maintenance, in previously untreated chronic lymphocytic leukemia Am J Hematol 90 2015 487 492
52. T. Robak, P. Smolewski, B. Cebula, O. Grzybowska-Izydorczyk, and J.Z. Blonski Rituximab plus cladribine with or without cyclophosphamide in patients with relapsed or refractory chronic lymphocytic leukemia Eur J Haematol 79 2007 107 113
53. N.E. Kay, S.M. Geyer, T.G. Call, and et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia Blood 109 2007 405 411
54. C. Reynolds, N. Di Bella, R.M. Lyons, and et al. A phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia Invest New Drugs 30 2012 1232 1240
55. Y. Zhou, G. Tang, L.J. Medeiros, and et al. Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma Mod Pathol 25 2012 237 245
56. A.S. Gerrie, C.L. Toze, K.M. Ramadan, and et al. Oral fludarabine and rituximab as initial therapy for chronic lymphocytic leukemia or small lymphocytic lymphoma: Population-based experience matches clinical trials Leuk Lymphoma 53 2012 77 82
57. W.G. Wierda, T.J. Kipps, J. Durig, and et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia Blood 117 2011 6450 6458
58. T. Shanafelt, M.C. Lanasa, T.G. Call, and et al. Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL) Cancer 119 2013 3788 3796
59. T. Elter, L. Gercheva-Kyuchukova, H. Pylylpenko, and et al. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: A randomised phase 3 trial Lancet Oncol 12 2011 1204 1213
60. T. Elter, R. James, R. Busch, and et al. Fludarabine and cyclophosphamide in combination with alemtuzumab in patients with primary high-risk, relapsed or refractory chronic lymphocytic leukemia Leukemia 26 2012 2549 2552
61. S. Lepretre, T. Aurran, B. Mahe, and et al. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial Blood 119 2012 5104 5110
62. C.H. Geisler, M.B. van T' Veer, J. Jurlander, and et al. Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL Blood 123 2014 3255 3262
63. S.A. Parikh, M.J. Keating, S. O'Brien, and et al. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia Blood 118 2011 2062 2068
64. K. Fischer, P. Cramer, R. Busch, and et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: A multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group J Clin Oncol 2012 3209 3216
65. B. Eichhorst, A.-M. Fink, R. Busch, and et al. Frontline chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) shows superior efficacy in comparison to bendamustine (B) and rituximab (BR) in previously untreated and physically fit patients (pts) with advanced chronic lymphocytic leukemia (CLL): Final analysis of an international, randomized study of the German CLL Study Group (GCLLSG) (CLL10 Study) Blood 2014 124
66. Offner F, Panagiotides P, Afanasyev B, et al. Ofatumumab and bendamustine combination therapy in patients with untreated and relapsed chronic lymphocytic leukemia: Initial results of the phase II study OMB115991. XV iwCLL Meeting Abstracts 2013:429.
67. B.F. Eichhorst, R. Busch, S. Stilgenbauer, and et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia Blood 114 2009 3382 3391
68. D. Catovsky, M. Else, and S. Richards Chlorambucil - still not bad: A reappraisal Clin Lymph Myeloma Leukemia 11 Suppl 1 2011 S2 S6
69. J.A. Woyach, A.S. Ruppert, K. Rai, and et al. Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: Results of sequential Cancer and Leukemia Group B studies J Clin Oncol 31 2013 440 447
70. P. Hillmen, J.G. Gribben, G.A. Follows, and et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study J Clin Oncol 32 2014 1236 1241
71. R. Foa, I. Del Giudice, A. Cuneo, and et al. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients Am J Hematol 89 2014 480 486
72. M. Patz, P. Isaeva, N. Forcob, and et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells Br J Haematol 152 2011 295 306
73. S. Dalle, L. Reslan, T. Besseyre de Horts, and et al. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101 Mol Cancer Ther 10 2011 178 185
74. E. Mossner, P. Brunker, S. Moser, and et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity Blood 115 2010 4393 4402
75. V. Goede, K. Fischer, R. Busch, and et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions N Engl J Med 370 2014 1101 1110
76. V. Goede, K. Fischer, A. Engelke, and et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: Updated results of the CLL11 study Leukemia 29 2015 1602 1604
77. P. Hillmen, T. Robak, A. Janssens, and et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): A randomised, multicentre, open-label phase 3 trial Lancet 385 2015 1873 1883
78. K.A. Foon, M. Boyiadzis, S.R. Land, and et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia J Clin Oncol 27 2009 498 503
79. K.A. Foon, D. Mehta, S. Lentzsch, and et al. Long-term results of chemoimmunotherapy with low-dose fludarabine, cyclophosphamide and high-dose rituximab as initial treatment for patients with chronic lymphocytic leukemia Blood 119 2012 3184 3185
80. S.G.D. Mulligan, P.W. Turner, M. Latimer, and et al. A randomised dose de-escalation study of oral fludarabine, ±oral cyclophosphamide and intravenous rituximab as first-line therapy of fit patients with chronic lymphocytic leukaemia (CLL) aged ≥65 years: Final analysis of response and toxicity Blood 124 2014 abstract 3325
81. C Dartigeas, E Van Den Neste, and C Berthou Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia Leuk Lymphoma 28 2015 1 7
82. L Smolej, Y Brychtova, M Doubek, and et al. Low-dose FCR is a safe and effective treatment option for elderly/comorbid patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Updated Results of Project Q-Lite By Czech CLL Study Group Blood 2014 124 abstract 4670
83. A-S Michallet, M. Aktan, A. Schuh, and et al. Rituximab in combination with bendamustine or chlorambucil for the treatment of chronic lymphocytic leukaemia: Primary results from the randomised phase IIIb MABLE study Leuk Lymphoma 56 Suppl 1 2015 abstract 88
84. S. Satram-Hoang, C. Reyes, K.Q. Hoang, F. Momin, and S. Skettino Treatment practice in the elderly patient with chronic lymphocytic leukemia-analysis of the combined SEER and Medicare database Ann Hematol 93 2014 1335 1344
85. J.E. Castro, D.F. James, J.D. Sandoval-Sus, and et al. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia Leukemia 23 2009 1779 1789
86. X.C. Badoux, M.J. Keating, S. Wen, and et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia Blood 118 2011 3489 3498
87. P. Strati, M.J. Keating, W.G. Wierda, and et al. Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia Blood 122 2013 734 737
88. D.F. James, L. Werner, J.R. Brown, and et al. Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: A multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium J Clin Oncol 32 2014 2067 2073
89. S. O'Brien, R.R. Furman, S.E. Coutre, and et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: An open-label, multicentre, phase 1b/2 trial Lancet Oncol 15 2014 48 58
90. J Burger, A Tedeschi, P Barr, and et al. Ibrutinib as initial therapy for patients with cronic lmphocytic lukemia N Engl J Med 373 2015 2425 2437
91. S.E. Herman, R.Z. Mustafa, J.A. Gyamfi, and et al. Ibrutinib inhibits B-cell receptor and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with chronic lymphocytic leukemia Blood 28 2014 2188 2196
92. J.C. Byrd, R.R. Furman, S.E. Coutre, and et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia N Engl J Med 369 2013 32 42
93. J.A. Burger, M.J. Keating, W.G. Wierda, and et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: A single-arm, phase 2 study Lancet Oncol 15 2014 1090 1099
94. R.R. Furman, J.P. Sharman, S.E. Coutre, and et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia N Engl J Med 370 2014 997 1007
95. J.R. Brown, J.C. Byrd, S.E. Coutre, and et al. Idelalisib, an inhibitor of phosphatidylinositol 3 kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia Blood 123 2014 3390 3397
96. Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015;125:2497-506
97. Dreger P, Schetelig J, Andersen N, et al. Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: Stem cell transplantation or novel agents? Blood 2014;124:3841-9
98. T. Robak, A. Dmoszynska, P. Solal-Celigny, and et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia J Clin Oncol 28 2010 1756 1765
99. P. Moreton, B. Kennedy, G. Lucas, and et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival J Clin Oncol 23 2005 2971 2979
100. J.A. Woyach, K. Smucker, L.L. Smith, and et al. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy Blood 123 2014 1810 1817