The spectrum of use of rituximab in chronic lymphocytic leukemia

OncoTargets and Therapy

Volumn 3, Issue , 2010, Pages 227-246

  Tedeschi, Alessandra ^a   Vismara, Eleonora ^a   Ricci, Francesca ^a   Morra, Enrica ^a   Montillo, Marco ^a  

^a OSPEDALE NIGUARDA CA GRANDA   (Italy)

Author keywords

B cell chronic lymphocytic leukemia; First line treatment; Refractory relapsed; Rituximab

Indexed keywords

ALEMTUZUMAB; BENDAMUSTINE; CHLORAMBUCIL; CLADRIBINE; CYCLOPHOSPHAMIDE; CYTARABINE; DEXAMETHASONE; FLUDARABINE; FOSCARNET; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; LENALIDOMIDE; LUMILIXIMAB; METHYLPREDNISOLONE; MITOXANTRONE; MONOCLONAL ANTIBODY; OXALIPLATIN; PENTOSTATIN; PURINE DERIVATIVE; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RITUXIMAB;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; B CELL LYMPHOMA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER GRADING; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; CELL LEVEL; CHRONIC LYMPHATIC LEUKEMIA; COMPLEMENT DEPENDENT CYTOTOXICITY; CONCENTRATION RESPONSE; CYTOMEGALOVIRUS INFECTION; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE SEQUENCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG USE; HUMAN; IMMUNE DEFICIENCY; INFECTION; LEUKEMIA REMISSION; LOW DRUG DOSE; LYMPHOCYTOMA; MAINTENANCE THERAPY; MINIMAL RESIDUAL DISEASE; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; NONHODGKIN LYMPHOMA; OPPORTUNISTIC INFECTION; OVERALL SURVIVAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; REVIEW; RISK BENEFIT ANALYSIS; SALVAGE THERAPY; SINGLE DRUG DOSE; SURVIVAL RATE; SURVIVAL TIME; TREATMENT DURATION; TREATMENT RESPONSE;

EID: 84863828006     PISSN: 11786930     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (136)

1. National Cancer Institute SEER Cancer Statistics Review 1975-2007. http://seer.cancer.gov/csr/1975_2007/. Accessed 2010 Oct 30.
2. Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet. 2008;371:1017-1029.
3. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198-206.
4. Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219-234.
5. Montillo M, Hamblin T, Hallek M, et al. Chronic lymphocytic leukemia: novel prognostic factors and their relevance for risk-adapted therapeutic strategies. Haematologica. 2005;90:391-399.
6. Montserrat E. Classical and new prognostic factors in chronic lymphocytic leukemia: where to now? Hematol J. 2002;3:7-9.
7. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343: 1910-1916.
8. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840-1847.
9. Hamblin T, Davis Z, Gardiner A, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848-1854.
10. Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003;348:1764-1775.
11. di Giovanni S, Valentini G, Carducci P, et al. Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia. Acta Haematol. 1989;81:181-185.
12. CLL Trialists' Collaborative Group. Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials. CLL Trialists' Collaborative Group. J Natl Cancer Inst. 1999;91: 861-868.
13. Cheson BD, Bennet JM, Grever M, et al. National Cancer Institutesponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996; 87:4990-4997.
14. Hallek M, Cheson BD, Catovsky D, 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. 2008;111:5446-5456.
15. Keating MJ, O'Brien S, Kantariian,et al. Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood. 1993;81:2878-2884.
16. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343:1750-1757.
17. Johnson S, Smith AG, Loffler H, 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. 1996;347:1432-1438.
18. Leporrier M, Chevret S, Cazin B, et al. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001;98:2319-2325.
19. Keating MJ, O'Brien S, Lerner S, et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood. 1998;92:1165-1171.
20. Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007; 370:230-239.
21. Bosch F, Ferrer A, Lopez-Guillermo A, et al. Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. Br J Haematol. 2002;119:976-984.
22. Steurer M, Pall G, Richards S, et al. Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: a systematic review and meta-analysis. Cancer Treat Rev. 2006;32:377-389.
23. Keating MJ, Coutrè S, Rai K, et al. Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. Clin Lymphoma. 2004;4:220-227.
24. Montserrat E. Rituximab in chronic lymphocytic leukemia. Semin Oncol. 2003;30:34-39.
25. Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin Cancer Res. 2001;7: 709-723.
26. di Gaetano N, Xiao Y, Erba E, et al. Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant ot the cytotoxic activity of either drug alone. Br J Haematol. 2001;114: 800-809.
27. Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975-980.
28. Robak T, Dmoszynska A, Solal-Celigny P, 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. 2010;28:1756-1765.
29. Hallek M. State-of-the-art treatment of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2009;440-449.
30. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005; 23:4079-4088.
31. Hallek M, Fingerle-Rowson G, Fink AM, et al. First-line treatment with fludarabine (f), cyclophosphamide (C), and rituximab (R) (FCR) improves overall survival (OS) in previously untreated patients (pts) with advanced chronic lymphocytic leukemia (CLL): results of a randomized phase III trial on behalf of an international group of investigators and the German CLL Study Group. Blood. 2009;114:Abstract 535.
32. Moreton P, Kennedy B, Lucas G, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005;23: 2971-2979.
33. Dreger P, Corradini P, Kimby E, et al. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia. 2007;21:12-17.
34. Tobinai K. Rituximab and other emerging antibodies as molecular targetbased therapy of lymphoma. Int J Clin Oncol. 2003;8:212-223.
35. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003;22:7359-7368.
36. Ginaldi L, de Martinis M, Matutes E, et al. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998;51: 364-369.
37. Glennie MJ, French RR, Cragg MS, et al. Mechanisms of killing by anti- CD20 monoclonal antibodies. Mol Immunol. 2007;44:3823-3837.
38. Cragg MS, Walshe CA, Ivanoy AO, et al. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005; 8:140-174.
39. Demidem A, Lam T, Alas S, et al. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997;12:177-186.
40. Manches O, Lui G, Chaperot L, et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood. 2003;101: 949-954.
41. Harjunpaa A, Junnikkala S, Meri S. Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms. Scand J Immunol. 2000;51:634-641.
42. Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99:754-758.
43. Farag SS, Flinn IW, Modali R, et al. Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia. Blood. 2004;103:1472-1474.
44. Treon SP, Mitsiades C, Mitsiades N, et al. Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies. J Immunother. 2001;24:263-271.
45. Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95: 3900-3908.
46. Golay J, Zaffaroni L, Vaccari T, et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood. 2000;95:3900-3908.
47. Pedersen IM, Kitada S, Schimmer A, et al. The triterpenoid CDDO induces apoptosis in refractory CLL B cells. Blood. 2002;100:2965-2972.
48. Selenko N, Majdic O, Jager U, et al. Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? J Clin Immunol. 2002;22:124-130.
49. Selenko N, Majdic O, Draxier S, et al. CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells. Leukemia. 2001;15: 1619-1626.
50. Maloney DG, Grillo-Lopez AJ, Bodkin DJ, et al. IDEC-C2B8: Results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997;15:3266-3274.
51. Foran JM, Rohatiner AZ, Cunningham D, et al. European phase II study of Rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma, immunocytoma and small B-cell lymphocytic lymphoma. J Clin Oncol. 2000;18:317-324.
52. McLaughlin P, Grillo-Lopez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program. J Clin Oncol.1998;16:2825-2833.
53. Winkler U, Jensen M, Manzke O, et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (Rituximab, IDEC-C2B8). Blood. 1999;94:2217-2224.
54. Nguyen DT, Amess JA, Doughty H, et al. IDEC-C2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin's lymphoma and lymphoproliferative disorders: Evaluation of response on 48 patients. Eur J Haematol.1999;62:76-82.
55. Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001;98:1326-1331.
56. Itala M, Geisler CH, Kimby E, et al. Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: results from a Nordic multicentre study. Eur J Haematol. 2002;69:129-134.
57. O'Brien SM, Kantarjian H, Thomas DA, et al. Rituximab doseescalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19: 2165-2170.
58. Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol. 2001;19:2153-2164.
59. Hainsworth JD, Litchy S, Barton JH, et al. Single-agent rituximab as firstline and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2003;21:1746-1751.
60. Thomas DA, O'Brien S, Giles FJ, et al. Single agent rituximab in early stage chronic lymphocytic leukemia. Blood. 2001;98:364a.
61. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343:1750-1757.
62. Perz J, Topaly J, Fruehauf S, et al. Level of CD20 expression and efficacy of rituximab treatment in patients with resistant or relapsing B-cell prolymphocytic leukaemia and B-cell chronic lymphocytic leukaemia. Leuk Lymphoma. 2002;43:149-151.
63. Manshouri T. Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood. 2003;101:2507-2513.
64. Maloney DG, Grillo-Lopez AJ, Bodkin DJ, et al. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol.1997;15:3266-3274.
65. Furlan A, Villanova F, Pietrogrande F, et al. Low-dose fludarabine increases rituximab cytotoxicity in B-CLL cells by triggering caspases activation in vitro. Leuk Lymphoma. 2010;51:107-113.
66. Chow KU, Sommerlad WD, Boehrer S, et al. Anti-CD20 antibody (IDEC-C2B8, rituximab) enhances efficacy of cytotoxic drugs on neoplastic lymphocytes in vitro: role of cytokines, complement, and caspases. Haematologica. 2002;87:33-43.
67. Byrd JC, Peterson BL, Morrison VA, 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. 2003;101:6-14.
68. Woyach JA, Ruppert AS, Heerema NA, et al. Treatment with fludarabine and rituximab produces extended overall survival (OS) and Progression- Free Survival (PFS) in chronic lymphocytic leukemia (CLL) without increased risk of second malignancy: long-term follow up of CALGB study 9712. Blood. 2009;114:Abstract 539.
69. Byrd JC, Rai K, Peterson BL, 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. 2005;105:49-53.
70. Schulz H, Klein SK, Rehwald U, et al. Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. Blood. 2002;100:3115-3120.
71. Hallek M, Schmitt B, Wilhelm M, et al. Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group. Br J Haematol. 2001;114:342-348.
72. Flinn IW, Byrd JC, Morrison C, et al. Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. Blood. 2000;96:71-75.
73. O'Brien SM, Kantarjian HM, Cortes J, et al. Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol. 2001;19:1414-1420.
74. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4070-4078.
75. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554-3561.
76. Rai KR, Freter CE, Mercier RJ, et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002;20:3891-3897.
77. Tsimberodou AM, Tam C, Abruzzo LV, et al. Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer. 2009;115:373-380.
78. Wierda W, O'Brien S, Faderl S, et al. A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine-based regimens. Cancer. 2006;106:337-345.
79. Hallek M, Fingerle-Rowson G, Fink AM, et al. Immunochemotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) versus fludarabine and cyclophosphamide (FC) improves response rates and progression-free survival (PFS) of previously untreated patients (pts) with advanced chronic lymphocytic leukemia (CLL). Blood. 2008; 112:Abstract 325.
80. Lepretre S, Aurran T, Mahe B, et al. Immunochemotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) versus fludarabine (F), cyclophosphamide (C) and mabcampath (Cam) (FCCam) in previously untreated patients (pts) with advanced B-chronic lymphocytic leukemia (B-CLL): experience on safety and efficacy within a randomised multicenter phase III trial of the French Cooperative Group on CLL and WM (FCGCLL/MW) and the "Groupe Ouest-Est d'Etudes Des Leucémies Aigües Et Autres Maladies Du sang" (GOELAMS):CLL2007FMP (for fit medically patients). Blood. 2009;114:Abstract 538.
81. Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009;27:498-503.
82. Lamanna N, Jurcic JG, Nov A, et al. Sequential therapy with fludarabine, high-dose cyclophosphamide, and rituximab in previously untreated patients with chronic lymphocytic leukemia produces high-quality responses: molecular remissions predict for durable complete responses. J Clin Oncol. 2009;27:491-497.
83. Weiss MA, Maslak PG, Jurcic JG, et al. Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia. J Clin Oncol. 2003;21: 1278-1284.
84. Lamanna N, Kalaycio M, Maslak P, et al. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006;24:1575-1581.
85. Kay NE, Geyer SM, Call TG, 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. 2007; 109:405-411.
86. Shanafelt TD, Lin T, Geyer SM, et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer. 2007;109:2291-2298.
87. Reynolds C, di Bella N, Lyons RM, et al. Phase III trial of fludarabine, cyclophosphamide, and rituximab vs pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia. Blood. 2008; 112:Abstract 126.
88. Kay NE, Wu W, Kabat B, et al. Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia. Cancer. 2010;116:2180-2187.
89. Robak T, Smolewski P, Cebula B, et al. Rituximab plus cladribine with or without cyclophosphamide in patients with relapsed or refractory chronic lymphocytic leukemia. Eur J Haematol. 2007;79: 107-113.
90. Bertazzoni P, Rabascio C, Gigli F, et al. Riruximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients. Leuk Lymphoma. 2010;51:1485-1493.
91. Montillo M, Ricci F, Tedeschi A, et al. Bendamustine: new perspective for an old drug in lymphoproliferative disorders. Expert Rev Hematol. 2010;3:131-148.
92. Fischer K, Stilgenbauer S, Schweighofer CD, et al. Bendamustine in combination with rituximab (BR) for patients with relapsed chronic lymphocytic Leukemia (CLL): a multicentre phase II trial of the German CLL Study Group (GCLLSG). Blood. 2008;112: Abstract 330.
93. Fischer K, Cramer P, Stilgenbauer S, et al. Bendamustine combined with rituximab (BR) in first-line therapy of advanced CLL: A multicenter phase II trial of the German CLL Study Group (GCLLSG). Blood. 2009;114:Abstract 205.
94. Weide R, Hess G, Koppler H, et al. High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma. 2007;48:1299-1306.
95. Hillmen P, Gribben JG, MD, Follows GA, et al. An open-label phase II study to investigate the safety and efficacy of rituximab plus chlorambucil in previously untreated patients with CD20-positive B-cell chronic lymphocytic leukaemia (CLL). Blood. 2009;114: Abstract 3428.
96. Bosch F, Ferrer A, Villamor N, et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication. Clin Cancer Res. 2008; 14:155-1561.
97. Hendry L, Bowen A, Matutes E, et al. Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma. Leuk Lymphoma. 2004;45:945-950.
98. Hillmen P, Pocock C, Cohen D, et al. NCRI CLL201 Trial: a randomized phase ii trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated CLL. Blood. 2007;110:Abstract 752.
99. Bosch F, Abrisqueta P, Villamor N, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol. 2009;27:4578-4584.
100. Faderl S, Wierda W, O'Brien S, et al. Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL, 70 years. Leuk Res. 2010;34:284-288.
101. Tsimberidou AM, Wierda W, Plunkett W, et al. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008;26(2):196-203.
102. Tsimberidou AM, O'Brien SM, Cortes JE, et al. Phase II study of fludarabine, cytarabine (Ara-C), cyclophosphamide, cisplatin and GM-CSF (FACPGM) in patients with Richter's syndrome or refractory lymphoproliferative disorders. Leuk Lymphoma. 2002;43: 767-772.
103. Giles FJ, O'Brien SM, Santini V, et al. Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: a phase II study. Leuk Lymphoma. 1999;36:57-65.
104. Tsimberidou AM, Wierda W, Plunkett W, et al. Oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy induces high response rates in agressive chronic lymphocytic Leukemia (CLL) and Richter's syndrome (RS). Blood. 2009;114:Abstract 3443.
105. Rossmann ED, Lundin J, Lenkei R, et al. Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies. Hematol J. 2001;2: 300-306.
106. Nabhan C, Patton D, Gordon LI, et al. A pilot trial of rituximab and alemtuzumab combination therapy in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Leuk Lymphoma. 2004;45:2269-2273.
107. Faderl S, Thomas DA, O'Brien S, et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood. 2003;101:3413-3415.
108. Faderl S, Ferrajoli A, Wierda W, et al. Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer. 2010;116:2360-2365.
109. Frankfurt O, Hamilton E, Duffey S, et al. Alemtuzumab and Rituximab Combination Therapy for Patients with Untreated CLL - a Phase II Trial. Blood. 2008;112:Abstract 2098.
110. Zent CS, Call TG, Shanafelt TD, et al. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer. 2008;113:2110-2118.
111. Wierda WG, O'Brien S, Faderl S, et al. Combined cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR), an active regimen for heavily treated patients with CLL. Blood. 2006;108: Abstract 31.
112. Parikh SA, Keating M, O'Brien S, et al. Frontline Combined Chemoimmunotherapy with Fludarabine, Cyclophosphamide, Alemtuzumab and Rituximab (CFAR) in High-Risk Chronic Lymphocytic Leukemia. Blood. 2009;114:Abstract 208.
113. Byrd JC, Kipps TJ, Flinn IW, et al. Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia. Blood. 2010;115:489-495.
114. Thornton PD, Hamblin M, Treleaven JG, et al. High dose methyl prednisolone in refractory chronic lymphocytic leukaemia. Leuk Lymphoma. 1999;34:167-170.
115. Thornton PD, Matutes E, Bosanquet AG, et al. High dose methylprednisolone can induce remissions in CLL patients with p53 abnormalities. Ann Hematol. 2003;82:759-765.
116. Castro JE, Sandoval-Sus JD, Bole J, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008; 22:2048-2053.
117. Quinn JP, Mohamedbhai S, Chipperfield K, et al. Efficacy of rituximab in combination with steroids in refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2008;49:1995-1998.
118. Bowen DA, Call TG, Jenkins GD, Zent CS, et al. Methylprednisolone- rituximab is an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia including those with unfavorable cytogenetic features. Leuk Lymphoma. 2007;48: 2412-2417.
119. Dungarwalla M, Evans SO, Riley U, et al. High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy. Haematologica. 2008;93:475-476.
120. Castro JE, Sandoval-Sus JD, Jain S, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009;23:1779-1789.
121. Venugopal P, Sivaraman S, Huang XK, et al. Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia. Leuk Res. 2000;24:411-415.
122. Voso MT, Pantel G, Rutella S, et al. Rituximab reduces the number of peripheral blood B-cells in vitro mainly by effector cell-mediated mechanisms. Haematologica. 2002;87:918-925.
123. Ferrajoli A. Incorporating the use of GM-CSF in the treatment of chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:514-516.
124. Ferrajoli A, Faderl S, O'Brien S, et al. Experience with fludarabine, cyclophosphamide, rituximab (FCR) plus GM-CSF in frontline therapy for chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 3173.
125. Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006;24: 5343-5349.
126. Ferrajoli A, Lee BN, Schlette EJ, et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008;111:5291-5297.
127. Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008;14: 4650-4657.
128. Ferrajoli A, Badoux XC, O'Brien S, et al. Combination Therapy with Lenalidomide and Rituximab in Patients with Relapsed Chronic Lymphocytic Leukemia (CLL). Blood. 2009;114:Abstract 206.
129. Ghielmini M, Schmitz SF, Cogliatti SB, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly × 4 schedule. Blood. 2004;103:4416-4423.
130. Salles GA, Seymour JF, Feugier P, et al. Rituximab maintenance for 2 years in patients with untreated high tumor burden follicular lymphoma after response to immunochemotherapy. J Clin Oncol. 2010; 28:8004.
131. van Oers MHJ, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006;108:3295-3301.
132. Del Poeta G, Del Principe MI, Buccisano F, et al. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer. 2008; 112:119-128.
133. Del Poeta G, Del Principe MI, Ragusa D, et al. Rituximab maintenance following chemoimmunotherapy improves outcome in B-cell chronic lymphocytic leukemia. Blood. 2009;114:Abstract 2364.
134. Srock S, Schriever F, Neubauer A, et al. Long-term treatment with rituximab is feasible in selected patients with B-CLL: responseadjusted low-dose maintenance treatment with rituximab in patients with relapsed B-CLL, who achieved a partial or minimal response to prior rituximab therapy. Leuk Lymphoma. 2007;48:905-911.
135. Abrisqueta P, Pereira A, Rozman C, et al. Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience. Blood, 2009;114:2044-2050.
136. Brenner H, Gonolons A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the early 21st century. Blood, 2008;111:4916-4921.