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What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?

  • Chronic Leukemias (S O’Brien, Section Editor)
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Abstract

Chronic lymphocytic leukemia (CLL) with 17p deletion or mutations of the TP53 gene has a very poor outcome. Optimal treatment of these patients remains a major clinical challenge, and disagreement on the optimal treatment approach exists. Conventional chemo-immunotherapy with rituximab in combination with purine analogues yields lower response-rates and less satisfactory results than for CLL patients with intact p53. Allogeneic stem cell transplantation may allow long-term remissions in this challenging group of patients. In this review, we will discuss current treatment options as well as experimental approaches in clinical trials for CLL patients with deleted or mutated TP53. Particular emphasis will be placed on novel agents with the potential to change clinical practice and future perspectives for the management of these “highest risk” patients.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 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(18):4079–88.

    Article  PubMed  CAS  Google Scholar 

  2. 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(4):975–80.

    Article  PubMed  CAS  Google Scholar 

  3. •• 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(9747):1164–74. This work presents the impact of the addition of rituximab to FC in a large prospective clinical trial. Additionally, response and outcome is demonstrated according to different prognostic parameters.

    Article  PubMed  CAS  Google Scholar 

  4. Zenz T, Eichhorst B, Busch R, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473–9.

    Article  PubMed  Google Scholar 

  5. Zenz T, Gribben JG, Hallek M, et al. Risk categories and refractory CLL in the era of chemoimmunotherapy. Blood. 2012;119(18):4101–7.

    Article  PubMed  CAS  Google Scholar 

  6. Sellner L, Dietrich S, Dreger P, et al. Can prognostic factors be used to direct therapy in chronic lymphocytic leukemia? Curr Hematol Malig Rep. 2012;7(1):3–12.

    Article  PubMed  Google Scholar 

  7. Isobe M, Emanuel BS, Givol D, et al. Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986;320(6057):84–5.

    Article  PubMed  CAS  Google Scholar 

  8. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88(3):323–31.

    Article  PubMed  CAS  Google Scholar 

  9. Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1):a001008.

    Article  PubMed  Google Scholar 

  10. Li FP, Fraumeni Jr JF, Mulvihill JJ, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988;48(18):5358–62.

    PubMed  CAS  Google Scholar 

  11. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910–6.

    Article  PubMed  CAS  Google Scholar 

  12. Grever MR, Lucas DM, Dewald GW, et al. Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol. 2007;25(7):799–804.

    Article  PubMed  CAS  Google Scholar 

  13. Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27(24):3994–4001.

    Article  PubMed  CAS  Google Scholar 

  14. Zenz T, Habe S, Denzel T, et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood. 2009;114(13):2589–97.

    Article  PubMed  CAS  Google Scholar 

  15. Zenz T, Krober A, Scherer K, et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood. 2008;112(8):3322–9.

    Article  PubMed  CAS  Google Scholar 

  16. Rossi D, Cerri M, Deambrogi C, 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. 2009;15(3):995–1004.

    Article  PubMed  CAS  Google Scholar 

  17. 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(12):5446–56.

    Article  PubMed  CAS  Google Scholar 

  18. Zenz T, Habe S, Denzel T, et al. How little is too much? p53 inactivation: from laboratory cutoff to biological basis of chemotherapy resistance. Leukemia. 2008;22(12):2257–8.

    Article  PubMed  CAS  Google Scholar 

  19. Pospisilova S, Gonzalez D, Malcikova J, et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia. 2012;26(7):1458–61.

    Article  PubMed  CAS  Google Scholar 

  20. Zenz T, Vollmer D, Trbusek M, et al. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia. 2010;24(12):2072–9.

    Article  PubMed  CAS  Google Scholar 

  21. Jethwa A, Hüllein J, Stolz T, et al. Genetic profiling in chronic lymphocytic leukemia. submitted. 2012.

  22. Zent CS, Call TG, Shanafelt TD, et al. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer. 2008;113(8):2110–8.

    Article  PubMed  CAS  Google Scholar 

  23. Best OG, Gardiner AC, Davis ZA, et al. A subset of Binet stage A CLL patients with TP53 abnormalities and mutated IGHV genes have stable disease. Leukemia. 2009;23(1):212–4.

    Article  PubMed  CAS  Google Scholar 

  24. Tam CS, Shanafelt TD, Wierda WG, et al. De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience. Blood. 2009;114(5):957–64.

    Article  PubMed  CAS  Google Scholar 

  25. Badoux XC, Keating MJ, Wierda WG. What is the best frontline therapy for patients with CLL and 17p deletion? Curr Hematol Malig Rep. 2011;6(1):36–46.

    Article  PubMed  Google Scholar 

  26. 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.

  27. Stilgenbauer S, Dohner H. Campath-1H-induced complete remission of chronic lymphocytic leukemia despite p53 gene mutation and resistance to chemotherapy. N Engl J Med. 2002;347(6):452–3.

    Article  PubMed  Google Scholar 

  28. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007;25(35):5616–23.

    Article  PubMed  CAS  Google Scholar 

  29. 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(10):3554–61.

    Article  PubMed  CAS  Google Scholar 

  30. O'Brien SM, Kantarjian HM, Thomas DA, et al. Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia. Cancer. 2003;98(12):2657–63.

    Article  PubMed  Google Scholar 

  31. •• Pettitt AR, Jackson R, Carruthers S, et al. Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial. J Clin Oncol. 2012;30(14):1647–55. This is a prospective trial that evaluatedalemtuzumab in combination with methylprednisolone in CLL patients with deletions of TP53.

    Article  PubMed  CAS  Google Scholar 

  32. Stilgenbauer S, Cymbalista F, Leblond V, et al. Alemtuzumab plus oral dexamethasone, followed by alemtuzumab maintenance or allogeneic transplantation in ultra high-risk CLL: updated results from a phase II study of the GCLLSG and FCGCLL/MW. ASH Annual Meeting Abstracts, submitted. 2012.

  33. Lepretre S, Aurran T, Mahe B, 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. 2012;119(22):5104–10.

    Article  PubMed  CAS  Google Scholar 

  34. Mossner E, Brunker P, Moser S, 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. 2010;115(22):4393–402.

    Article  PubMed  CAS  Google Scholar 

  35. Smolej L, Doubek M, Panovska A, et al. Rituximab in combination with high-dose dexamethasone for the treatment of relapsed/refractory chronic lymphocytic leukemia. Leuk Res. 2012;36(10):1278–82.

    Article  PubMed  CAS  Google Scholar 

  36. Badoux XC, Keating MJ, Wen S, et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood. 2011;118(13):3489–98.

    Article  PubMed  CAS  Google Scholar 

  37. James DF, Brown JR, Werner L, et al. Lenalidomide and Rituximab for the Initial Treatment of Patients with Chronic Lymphocytic Leukemia (CLL) a multicenter study of the CLL Research Consortium. ASH Annual Meeting Abstracts. 2011;118(21):291.

    Google Scholar 

  38. Goede V, Fischer K, Busch R, et al. Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: Results of the CLL11 (BO21004) safety run-in. Leukemia. 2012.

  39. Zenz T, Busch R, Fink A, et al. Genetics of patients with F-refractory CLL or early relapse after FC or FCR: results from the CLL8 Trial of the GCLLSG. ASH Annual Meeting Abstracts. 2010;116(21):2427.

    Google Scholar 

  40. Brown JR. The treatment of relapsed refractory chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2011;2011:110–8.

    Article  PubMed  Google Scholar 

  41. Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 2011;117(11):3016–24.

    Article  PubMed  CAS  Google Scholar 

  42. Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011;29(26):3559–66.

    Article  PubMed  CAS  Google Scholar 

  43. Elter T, James R, Busch R, et al. Fludarabine and cyclophosphamide in combination with alemtuzumab (FCCam) in patients with primary high-risk, relapsed or refractory chronic lymphocytic leukemia. Leukemia. 2012.

  44. Montillo M, Tedeschi A, Petrizzi VB, et al. An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia. Blood. 2011;118(15):4079–85.

    Article  PubMed  CAS  Google Scholar 

  45. Badoux XC, Keating MJ, Wang X, et al. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia. Blood. 2011;118(8):2085–93.

    Article  PubMed  CAS  Google Scholar 

  46. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749–55.

    Article  PubMed  CAS  Google Scholar 

  47. Wierda WG, Padmanabhan S, Chan GW, et al. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood. 2011;118(19):5126–9.

    Article  PubMed  CAS  Google Scholar 

  48. 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(11):5291–7.

    Article  PubMed  CAS  Google Scholar 

  49. Sorror ML, Storer BE, Sandmaier BM, et al. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. 2008;26(30):4912–20.

    Article  PubMed  Google Scholar 

  50. •• Dreger P, Dohner H, Ritgen M, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116(14):2438–47. This is a prospective trial for poor risk CLL who underwent alloSCT including CLL patients with 17p-.

    Article  PubMed  CAS  Google Scholar 

  51. Sorror ML, Storer BE, Maloney DG, et al. Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood. 2008;111(1):446–52.

    Article  PubMed  CAS  Google Scholar 

  52. Schetelig J, van Biezen A, Brand R, et al. Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol. 2008;26(31):5094–100.

    Article  PubMed  Google Scholar 

  53. Herth I, Dietrich S, Hegenbart U, et al. First evidence that alloSCT can improve the natural course of poor-risk chronic lymphocytic leukaemiaas defined by the EBMT consensus criteria: a retrospective donor versus no donor comparison. EBMT Annual Meeting Abstract. 2012.

  54. Zenz T, Dreger P, Dietrich S, et al. Allogeneic stem cell transplantation can overcome the adverse prognostic impact of TP53 mutation in Chronic Lymphocytic Leukemia (CLL): results from the GCLLSG CLL3x Trial. ASH Annual Meeting Abstracts. 2010;116(21):2357.

    Google Scholar 

  55. Sorror ML, Storer B, Sandmaier BM, et al. Impacts of cytogenetic abnormalities and prior alemtuzumab on outcomes of patients (pts) with High-Risk Chronic Lymphocytic Leukemia (CLL) given nonmyeloablative allogeneic Hematopoietic Cell Transplantation (HCT). ASH Annual Meeting Abstracts. 2010;116(21):2364.

    Google Scholar 

  56. 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(1):12–7.

    Article  PubMed  CAS  Google Scholar 

  57. •• Bottcher S, Ritgen M, Fischer K, 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. 2012;30(9):980–8. This work highlights the impact of MRD quantification on response duration and survival in a large prospective trail.

    Article  PubMed  Google Scholar 

  58. 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(13):2971–9.

    Article  PubMed  CAS  Google Scholar 

  59. Montillo M, Tedeschi A, Miqueleiz S, et al. Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia. J Clin Oncol. 2006;24(15):2337–42.

    Article  PubMed  CAS  Google Scholar 

  60. Schweighofer CD, Ritgen M, Eichhorst BF, et al. Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG). Br J Haematol. 2009;144(1):95–8.

    Article  PubMed  CAS  Google Scholar 

  61. Wierda WG, Kipps TJ, Keating MJ, et al. Self-administered, subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia. Cancer. 2011;117(1):116–24.

    Article  PubMed  CAS  Google Scholar 

  62. Wendtner CM, Ritgen M, Schweighofer CD, et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission—experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia. 2004;18(6):1093–101.

    Article  PubMed  CAS  Google Scholar 

  63. Lin TS, Donohue KA, Byrd JC, et al. Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101. J Clin Oncol. 2010;28(29):4500–6.

    Article  PubMed  CAS  Google Scholar 

  64. 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(1):119–28.

    Article  PubMed  Google Scholar 

  65. Woyach JA, Lozanski G, Ruppert AS, et al. Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features. Leukemia. 2012;26(6):1442–4.

    Article  PubMed  CAS  Google Scholar 

  66. Tong WG, Chen R, Plunkett W, et al. Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. J Clin Oncol. 2010;28(18):3015–22.

    Article  PubMed  CAS  Google Scholar 

  67. Jones J, Flynn JM, Andritsos L, et al. Phase I Study of the Cyclin-Dependent Kinase (CDK) Inhibitor Dinaciclib (SCH 727965) in Patients (PTS) with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL). EHA Annual Meeting Abstract. 2012.

  68. Blum KA, Ruppert AS, Woyach JA, et al. Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol. Leukemia. 2011;25(9):1444–51.

    Article  PubMed  CAS  Google Scholar 

  69. Buggins AG, Pepper CJ. The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. Leuk Res. 2010;34(7):837–42.

    Article  PubMed  CAS  Google Scholar 

  70. O'Brien SM, Claxton DF, Crump M, et al. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood. 2009;113(2):299–305.

    Article  PubMed  Google Scholar 

  71. Brown JR, Tesar B, Werner L, et al. Obatoclax in combination with Fludarabine and Rituximab (FR) is well-tolerated and shows promising clinical activity in relapsed CLL/SLL. ASH Annual Meeting Abstracts. 2011;118(21):2865.

    Google Scholar 

  72. Roberts AW, Seymour JF, Brown JR, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012;30(5):488–96.

    Article  PubMed  CAS  Google Scholar 

  73. Kipps TJ, Swinnen LJ, Wierda WG, et al. Navitoclax (ABT-263) plus Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR): A Phase 1 study in patients with relapsed/refractory Chronic Lymphocytic Leukemia (CLL). ASH Annual Meeting Abstracts. 2011;118(21):3904.

    Google Scholar 

  74. Roberts A, Davids M, Mahadevan D, et al. Selective Inhibition of Bcl-2 is Active Against Chronic Lymphocytic Leukemia (CLL): first clinical experience with the BH3-Mimetic Abt-199. EHA annual meeting. 2012.

  75. Minden MD, Ubelhart R, Schneider D, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012.

  76. Wiestner A. Emerging role of kinase targeted strategies in chronic lymphocytic leukemia. Blood. 2012.

  77. Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13):2578–85.

    Article  PubMed  CAS  Google Scholar 

  78. Jou ST, Carpino N, Takahashi Y, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol. 2002;22(24):8580–91.

    Article  PubMed  CAS  Google Scholar 

  79. Coutre SE, Byrd JC, Furman RR, et al. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. ASCO Annual Meeting Abstract. 2011.

  80. Cheson BD, Byrd JC, Rai KR, et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012;30(23):2820–2.

    Article  PubMed  CAS  Google Scholar 

  81. O’Brien S, Furman R, Coutre S, et al. The Bruton’s Tyrosine Kinase Inhibitor Ibrutinib is Highly Active and Tolerable in Relapsed or Refractory (R/R) and Treatment Naive (TN) CLL Patients, Updated Results of a Phase IB/II study EHA Annual Meeting Abstract. 2012.

  82. Badoux XC, Keating MJ, O'Brien S, et al. Final analysis of a Phase 2 study of lenalidomide and rituximab in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL). ASH Annual Meeting Abstracts. 2011;118(21):980.

    Google Scholar 

  83. Furman RR, Barrientos JC, Sharman JP, et al. A phase I/II study of the selective phosphatidylinositol 3-kinase-delta (PI3K) inhibitor, GS-1101 (CAL-101), with ofatumumab in patients with previously treated chronic lymphocytic leukemia (CLL). ASCO Annual Meeting Abstract. 2012.

  84. Sharman J, de Vos S, Leonard JP, et al. A Phase 1 study of the selective phosphatidylinositol 3-Kinase-Delta (PI3K{delta}) inhibitor, CAL-101 (GS-1101), in combination with rituximab and/or bendamustine in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL). ASH Annual Meeting Abstracts. 2011;118(21):1787.

    Google Scholar 

  85. O'Brien SM, Barrientos JC, Flinn IW, et al. Combination of the Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 with bendamustine (B)/rituximab (R) (BR) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): interim results of a phase Ib/II study. ASCO Annual Meeting Abstract. 2012.

  86. Jaglowski SM, Jones JA, Flynn JM, et al. A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI-32765 and ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. ASCO Annual Meeting Abstract. 2012.

  87. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7.

    Article  PubMed  CAS  Google Scholar 

  88. Dietrich S, Glimm H, Andrulis M, et al. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med. 2012;366(21):2038–40.

    Article  PubMed  Google Scholar 

  89. 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(1):155–61.

    Article  PubMed  CAS  Google Scholar 

  90. Eichhorst BF, 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(16):3382–91.

    Article  PubMed  CAS  Google Scholar 

  91. Robak T, Jamroziak K, Gora-Tybor J, et al. Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study). J Clin Oncol. 2010;28(11):1863–9.

    Article  PubMed  CAS  Google Scholar 

  92. Cencini E, Sozzi E, Sicuranza A, et al. A pilot monocentric analysis of efficacy and safety of Fludarabine-Campath combination (Flucam) as first line treatment in elderly patients with chronic lymphocytic leukaemia and Tp53 disfunction. Br J Haematol. 2011;154(2):271–4.

    Article  PubMed  Google Scholar 

  93. Parikh SA, Keating MJ, O'Brien S, et al. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia. Blood. 2011;118(8):2062–8.

    Article  PubMed  CAS  Google Scholar 

  94. • Wierda WG, Kipps TJ, Durig J, et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood. 2011;117(24):6450–8. In this article, the efficacy of ofatumumab in refractory CLL including patients with 17p- is demonstrated.

    Article  PubMed  CAS  Google Scholar 

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Disclosure Statement

L. Sellner: nothing to disclose; S. Denzinger: nothing to disclose; S. Dietrich: nothing to disclose; H. Glimm: nothing to disclose; O. Merkel: nothing to disclose; P. Dreger: nothing to disclose; T. Zenz: received consulting fee or honorarium from GSK; support for travel to meetings for the study or other purposes received by GSK and Roche; payment for lectures, including service on speakers bureaus, received by Celgene; received patents from Boehringer.

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  1. Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany

    L. Sellner, H. Glimm, O. Merkel & T. Zenz

  2. Department of Medicine V, Heidelberg University Medical Center, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    L. Sellner, S. Denzinger, S. Dietrich, P. Dreger & T. Zenz

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  1. L. Sellner
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Sellner, L., Denzinger, S., Dietrich, S. et al. What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?. Curr Hematol Malig Rep 8, 81–90 (2013). https://doi.org/10.1007/s11899-012-0143-0

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  • DOI: https://doi.org/10.1007/s11899-012-0143-0

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