Fludarabine: A review of the clear benefits and potential harms

Leukemia Research

Volumn 37, Issue 9, 2013, Pages 986-994

  Lukenbill, Joshua ^a   Kalaycio, Matt ^a  

^a TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Adverse effects; Fludarabine; Myelosuppression; Secondary malignancy; Toxicities

Indexed keywords

BENDAMUSTINE; CD38 ANTIGEN; CHLORAMBUCIL; CYCLOPHOSPHAMIDE; FLAVOPIRIDOL; FLUDARABINE; GRANULOCYTE COLONY STIMULATING FACTOR; IBRUTINIB; IDELALISIB; LENALIDOMIDE; OFATUMUMAB; PENTOSTATIN; PREDNISOLONE; RITUXIMAB;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; BACTERIAL INFECTION; BLOOD CELL COUNT; BLOOD TOXICITY; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER REGRESSION; CANCER SURVIVAL; CHEMOPROPHYLAXIS; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL EFFECTIVENESS; CYTOPENIA; DOSE RESPONSE; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG TOLERABILITY; FATIGUE; GASTROINTESTINAL SYMPTOM; GLOMERULUS FILTRATION RATE; HEMATOLOGIC DISEASE; HUMAN; INFECTION; KIDNEY FAILURE; LEUKOPENIA; LUNG INFECTION; LYMPHOCYTOPENIA; METASTASIS; MOLECULAR DYNAMICS; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; MYCOSIS; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; NEUTROPHIL; NONHUMAN; OVERALL SURVIVAL; PATIENT MONITORING; PATIENT SELECTION; PNEUMONIA; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RECURRENT CANCER; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; SIDE EFFECT; STEM CELL MOBILIZATION; SURVIVAL RATE; THERAPY DELAY; THROMBOCYTE COUNT; THROMBOCYTOPENIA; VIRUS INFECTION;

ADVERSE EFFECTS; FLUDARABINE; MYELOSUPPRESSION; SECONDARY MALIGNANCY; TOXICITIES;

HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LEUKEMIA, MYELOID, ACUTE; MYELODYSPLASTIC SYNDROMES; PROGNOSIS; VIDARABINE;

EID: 84880959171     PISSN: 01452126     EISSN: 18735835     Source Type: Journal    
DOI: 10.1016/j.leukres.2013.05.004     Document Type: Review

References (93)

1. Han T., Rai K.R. Management of chronic lymphocytic leukemia. Hematol Oncol Clin North Am 1990, 4:431-445.
2. Montserrat E., Rozman C. Chronic lymphocytic leukaemia treatment. Blood Rev 1993, 7:164-175.
3. Sawitsky A., Rai K.R., Glidewell O., Silver R.T. Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia. Blood 1977, 50:1049-1059.
4. Montserrat E., Alcala A., Parody R., et al. Treatment of chronic lymphocytic leukemia in advanced stages. A randomized trial comparing chlorambucil plus prednisone versus cyclophosphamide, vincristine, and prednisone. Cancer 1985, 56:2369-2375.
5. Raphael B., Andersen J.W., Silber R., 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 1991, 9:770-776.
6. 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.
7. Comparison of fludarabine, cyclophosphamide/doxorubicin/prednisone, and cyclophosphamide/doxorubicin/vincristine/prednisone in advanced forms of chronic lymphocytic leukemia: preliminary results of a controlled clinical trial. The French Cooperative Group on Chronic Lymphocytic Leukemia. Semin Oncol 1993, 20:21-23.
8. Effectiveness of "CHOP" regimen in advanced untreated chronic lymphocytic leukaemia. French Cooperative Group on Chronic Lymphocytic Leukaemia. Lancet 1986, 1:1346-1349.
9. Keating M.J., Scouros M., Murphy S., et al. Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukemia. Leukemia 1988, 2:157-164.
10. Huguley C.M. Treatment of chronic lymphocytic leukemia. Cancer Treat Rev 1977, 4:261-273.
11. Keller J.W., Knospe W.H., Raney M., et al. Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy. A Southeastern Cancer Study Group Trial. Cancer 1986, 58:1185-1192.
12. Grever M.R., Kopecky K.J., Coltman C.A., et al. Fludarabine monophosphate: a potentially useful agent in chronic lymphocytic leukemia. Nouv Rev Fr Hematol 1988, 30:457-459.
13. Keating M.J., Kantarjian H., Talpaz M., et al. Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 1989, 74:19-25.
14. Zinzani P.L., Bendandi M., Magagnoli M., et al. Long-term follow-up after fludarabine treatment in pretreated patients with chronic lymphocytic leukemia. Haematologica 2000, 85:1135-1139.
15. 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.
16. Badoux X.C., Keating M.J., Wang X., et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood 2011, 117:3016-3024.
17. Hiddemann W., Rottmann R., Wormann B., et al. Treatment of advanced chronic lymphocytic leukemia by fludarabine. Results of a clinical phase-II study. Ann Hematol 1991, 63:1-4.
18. Keating M.J., O'Brien S., Kantarjian H., et al. Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood 1993, 81:2878-2884.
19. O'Brien S., Kantarjian H., Beran M., et al. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 1993, 82:1695-1700.
20. Keating M.J., 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.
21. 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.
22. Rai K.R., Peterson B.L., Appelbaum F.R., et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000, 343:1750-1757.
23. Eichhorst B.F., Busch R., Hopfinger G., et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood 2006, 107:885-891.
24. Eichhorst B.F., Busch R., Stilgenbauer S., 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 2009, 114:3382-3391.
25. O'Brien S.M., Kantarjian H.M., Cortes J., et al. Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol 2001, 19:1414-1420.
26. 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.
27. Flinn I.W., Neuberg D.S., Grever M.R., 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 2007, 25:793-798.
28. Woyach J.A., Ruppert A.S., Heerema N.A., 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 2011, 29:1349-1355.
29. Keating M.J., 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.
30. Hallek M., Fischer K., Fingerle-Rowson G., et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010, 376:1164-1174.
31. Tam C.S., 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.
32. Gandhi V., Plunkett W. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet 2002, 41:93-103.
33. Danhauser L., Plunkett W., Keating M., Cabanillas F. 9-Beta-d-arabinofuranosyl-2-fluoroadenine 5'-monophosphate pharmacokinetics in plasma and tumor cells of patients with relapsed leukemia and lymphoma. Cancer Chemother Pharmacol 1986, 18:145-152.
34. Barrueco J.R., Jacobsen D.M., Chang C.H., Brockman R.W., Sirotnak F.M. Proposed mechanism of therapeutic selectivity for 9-beta-d-arabinofuranosyl-2-fluoroadenine against murine leukemia based upon lower capacities for transport and phosphorylation in proliferative intestinal epithelium compared to tumor cells. Cancer Res 1987, 47:700-706.
35. Pettitt A.R. Mechanism of action of purine analogues in chronic lymphocytic leukaemia. Br J Haematol 2003, 121:692-702.
36. Avramis V.I., Plunkett W. Metabolism and therapeutic efficacy of 9-beta-d-arabinofuranosyl-2-fluoroadenine against murine leukemia P388. Cancer Res 1982, 42:2587-2591.
37. Moufarij M.A., Sampath D., Keating M.J., Plunkett W. Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal. Blood 2006, 108:4187-4193.
38. Yamauchi T., Nowak B.J., Keating M.J., Plunkett W. DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine. Clin Cancer Res 2001, 7:3580-3589.
39. Sandoval A., Consoli U., Plunkett W. Fludarabine-mediated inhibition of nucleotide excision repair induces apoptosis in quiescent human lymphocytes. Clin Cancer Res 1996, 2:1731-1741.
40. Morgan S.J., Seymour J.F., Grigg A., et al. Predictive factors for successful stem cell mobilization in patients with indolent lymphoproliferative disorders previously treated with fludarabine. Leukemia 2004, 18:1034-1038.
41. Smith S.M., Le Beau M.M., Huo D., et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 2003, 102:43-52.
42. Lam C.C., Ma E.S., Kwong Y.L. Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia. Am J Hematol 2005, 79:288-290.
43. Smith M.R., Neuberg D., Flinn I.W., et al. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997. Blood 2011, 118(September (13)):3525-3527. [Epub 2011 July 29].
44. Lichtman S.M., Etcubanas E., Budman D.R., et al. The pharmacokinetics and pharmacodynamics of fludarabine phosphate in patients with renal impairment: a prospective dose adjustment study. Cancer Invest 2002, 20:904-913.
45. Tsimberidou A.M., Younes A., Romaguera J., et al. Immunosuppression and infectious complications in patients with stage IV indolent lymphoma treated with a fludarabine, mitoxantrone, and dexamethasone regimen. Cancer 2005, 104:345-353.
46. McLaughlin P., Hagemeister F.B., Romaguera J.E., et al. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol 1996, 14:1262-1268.
47. Kowal M., Dmoszynska A., Lewandowski K., et al. Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study. Leuk Lymphoma 2004, 45:1159-1165.
48. Redman J.R., Cabanillas F., Velasquez W.S., et al. Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma. J Clin Oncol 1992, 10:790-794.
49. Byrd J.C., Hargis J.B., Kester K.E., Hospenthal D.R., Knutson S.W., Diehl L.F. Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis. Am J Hematol 1995, 49:135-142.
50. Gill S., Carney D., Ritchie D., et al. The frequency, manifestations, and duration of prolonged cytopenias after first-line fludarabine combination chemotherapy. Ann Oncol 2010, 21:331-334.
51. Martell R.E., Peterson B.L., Cohen H.J., et al. Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study. Cancer Chemother Pharmacol 2002, 50:37-45.
52. Polizzotto M.N., Tam C.S., Milner A., et al. The influence of increasing age on the deliverability and toxicity of fludarabine-based combination chemotherapy regimens in patients with indolent lymphoproliferative disorders. Cancer 2006, 107:773-780.
53. Lukenbill J., Elson P., Kalaycio M. Consequences of chemotherapy induced myelosuppression in patients with chronic lymphocytic leukemia (CLL). Blood 2010, 116:4637. [Abstract].
54. Visani G., Lemoli R.M., Tosi P., et al. Fludarabine-containing regimens severely impair peripheral blood stem cells mobilization and collection in acute myeloid leukaemia patients. Br J Haematol 1999, 105:775-779.
55. Tournilhac O., Cazin B., Lepretre S., et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004, 103:363-365.
56. Waterman J., Rybicki L., Bolwell B., et al. Fludarabine as a risk factor for poor stem cell harvest, treatment-related MDS and AML in follicular lymphoma patients after autologous hematopoietic cell transplantation. Bone Marrow Transplant 2011.
57. Carney D.A., Westerman D.A., Tam C.S., et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy. Leukemia 2010, 24:2056-2062.
58. Lysak D., Koza V., Steinerova K., Jindra P., Vozobulova V., Schutzova M. Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment. Ann Hematol 2005, 84:456-461.
59. Nichols G.L., Skerrett D.L. Peripheral blood stem cell mobilization and harvesting after fludarabine therapy for low-grade lymphoma and chronic lymphocytic leukemia. Stem Cells Dev 2005, 14:3-5.
60. Michallet M., Thiebaut A., Dreger P., et al. Peripheral blood stem cell (PBSC) mobilization and transplantation after fludarabine therapy in chronic lymphocytic leukaemia (CLL): a report of the European Blood and Marrow Transplantation (EBMT) CLL subcommittee on behalf of the EBMT Chronic Leukaemias Working Party (CLWP). Br J Haematol 2000, 108:595-601.
61. Friedberg J.W. Secondary malignancies after therapy of indolent non-Hodgkin's lymphoma. Haematologica 2008, 93:336-338.
62. Cheson B.D., Vena D.A., Barrett J., Freidlin B. Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias. J Clin Oncol 1999, 17:2454-2460.
63. Berger M.G., Berger J., Richard C., et al. Preferential sensitivity of hematopoietic (HPs) and mesenchymal (MPs) progenitors to fludarabine suggests impaired bone marrow niche and HP mobilization. Leukemia 2008, 22:2131-2134.
64. Eissner G., Multhoff G., Gerbitz A., et al. Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide. Blood 2002, 100:334-340.
65. Sacchi S., Marcheselli L., Bari A., et al. Secondary malignancies after treatment for indolent non-Hodgkin's lymphoma: a 16-year follow-up study. Haematologica 2008, 93:398-404.
66. Kalaycio M., Rybicki L., Pohlman B., et al. Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia. J Clin Oncol 2006, 24:3604-3610.
67. Laurenti L., Tarnani M., Chiusolo P., et al. Low incidence of secondary neoplasia after autotransplantation for lymphoproliferative disease: the role of pre-transplant therapy. Clin Transplant 2008, 22:191-199.
68. Misgeld E., Germing U., Aul C., Gattermann N. Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma. Leuk Res 2001, 25:95-98.
69. Morrison V.A., Rai K.R., Peterson B.L., et al. Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an Intergroup Study, Cancer and Leukemia Group B 9011. J Clin Oncol 2002, 20:3878-3884.
70. Tam C.S., Seymour J.F., Prince H.M., et al. Treatment-related myelodysplasia following fludarabine combination chemotherapy. Haematologica 2006, 91:1546-1550.
71. Armitage J.O., Carbone P.P., Connors J.M., Levine A., Bennett J.M., Kroll S. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol 2003, 21:897-906.
72. Bowcock S.J., Rassam S.M., Lim Z., Ward S.M., Ryali M.M., Mufti G.J. High incidence of therapy-related myelodysplasia and acute leukaemia in general haematology clinic patients treated with fludarabine and cyclophosphamide for indolent lymphoproliferative disorders. Br J Haematol 2006, 134:242-243.
73. Vardiman J.W., Thiele J., Arber D.A., et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009, 114:937-951.
74. Saso R., Kulkarni S., Mitchell P., et al. Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma. Br J Cancer 2000, 83:91-94.
75. O'Brien S., Kantarjian H., Beran M., et al. Fludarabine and granulocyte colony-stimulating factor (G-CSF) in patients with chronic lymphocytic leukemia. Leukemia 1997, 11:1631-1635.
76. Freifeld A.G., Bow E.J., Sepkowitz K.A., et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011, 52:e56-e93.
77. Sauter C., Lamanna N., Weiss M.A. Pentostatin in chronic lymphocytic leukemia. Expert Opin Drug Metab Toxicol 2008, 4:1217-1222.
78. Dillman R.O., Mick R., McIntyre O.R. Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia Group B. J Clin Oncol 1989, 7:433-438.
79. Kay N.E., Geyer S.M., Call T.G., 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.
80. Kay N.E., 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.
81. 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.
82. Reynolds C., Di Bella N., Lyons R.M., 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 2012, 30:1232-1240.
83. Shanafelt T.D., Lin T., Geyer S.M., et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer 2007, 109:2291-2298.
84. Lathia C., Fleming G.F., Meyer M., Ratain M.J., Whitfield L. Pentostatin pharmacokinetics and dosing recommendations in patients with mild renal impairment. Cancer Chemother Pharmacol 2002, 50:121-126.
85. Cheson B.D., Rummel M.J. Bendamustine: rebirth of an old drug. J Clin Oncol 2009, 27:1492-1501.
86. Knauf W.U., Lissichkov T., Aldaoud A., et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009, 27:4378-4384.
87. Fischer K., Cramer P., Busch R., 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.
88. Badoux X.C., Keating M.J., Wen S., et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood 2011, 118(September (13)):3489-3498. [Epub 2011 July 1]. 10.1182/blood-2011-03-339077.
89. Badoux X.C., Keating M.J., Wen S., et al. Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol 2013, 31(February (5)):584-591. [Epub 2012 December 26]. 10.1200/JCO.2012.42.8623.
90. Ferrajoli A., O'Brien S., Wierda W.G., et al. Combination therapy with ofatumumab and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL). ASH Annual Meeting Abstracts 2011, 118:1788.
91. Stephens D.M., Ruppert A.S., Blum K., et al. Flavopiridol treatment of patients aged 70 or older with refractory or relapsed chronic lymphocytic leukemia is a feasible and active therapeutic approach. Haematologica 2012, 97(March (3)):423-427. [Epub 2012 January 22]. 10.3324/haematol.2011.047324.
92. O'Brien S., Burger J.A., Blum K.A., et al. The Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 induces durable responses in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): follow-up of a phase Ib/II study. ASH Annual Meeting Abstracts 2011, 118:983.
93. Byrd J.C., Blum K.A., Burger J.A., Coutre S.E. Activity and tolerability of the Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): interim results of a phase Ib/II study. ASCO Meeting Abstracts 2011 2011, 29:6508.