ESMO guidelines consensus conference on malignant lymphoma 2011 part 1: Diffuse large B-cell lymphoma (DLBCL), Follicular Lymphoma (FL) and Chronic Lymphocytic Leukemia (CLL)

Annals of Oncology

Volumn 24, Issue 3, 2013, Pages 561-576

  Ghielmini, M ^a   Vitolo, U ^b   Kimby, E ^c   Montoto, S ^d   Walewski, J ^e   Pfreundschuh, M ^f   Federico, M ^g   Hoskin, P ^h   McNamara, C ⁱ   Caligaris Cappio, F ^j   Stilgenbauer, S ^k   Marcus, R ^l   Trneny, M ^m   Dreger, P ⁿ   Montserrat, E ^o   Dreyling, M ^p  

^a OSPEDALE SAN GIOVANNI   (Switzerland)

^b MOLINETTE HOSPITAL   (Italy)

^c KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^d QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^e INSTITUTE OF ONCOLOGY   (Poland)

^f University Medicine of Saarland   (Germany)

^g UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^h Department of Hematology   (Italy)

ⁱ ROYAL FREE HOSPITAL   (United Kingdom)

^j VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^k UNIVERSITY HOSPITAL ULM   (Germany)

^l KING'S COLLEGE LONDON   (United Kingdom)

^m CHARLES UNIVERSITY   (Czech Republic)

ⁿ UNIVERSITY OF HEIDELBERG   (Germany)

^o UNIVERSITY OF BARCELONA   (Spain)

^p LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

more..

Author keywords

Chronic lymphocytic; Consensus conference; Diffuse large B cell lymphoma; Follicular lymphoma; Leukemia; Treatment

Indexed keywords

ALEMTUZUMAB; ANTINEOPLASTIC METAL COMPLEX; BENDAMUSTINE; BLEOMYCIN; CARBOPLATIN; CHLORAMBUCIL; CISPLATIN; CORTICOSTEROID; CYCLOPHOSPHAMIDE; CYTARABINE; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; FLAVOPIRIDOL; FLUDARABINE; FLUOROURACIL; GEMCITABINE; IFOSFAMIDE; IMMUNOSUPPRESSIVE AGENT; LENALIDOMIDE; METHOTREXATE; MITOXANTRONE; OFATUMUMAB; PENTOSTATIN; PREDNISONE; PURINE DERIVATIVE; RITUXIMAB; UNINDEXED DRUG; VINCRISTINE; VINDESINE;

ARTICLE; AUTOIMMUNE CYTOPENIA; CANCER THERAPY; CHRONIC LYMPHATIC LEUKEMIA; CONSENSUS; CYTOPENIA; DRUG MEGADOSE; EVIDENCE BASED PRACTICE; FOLLICULAR LYMPHOMA; HUMAN; IDIOPATHIC THROMBOCYTOPENIC PURPURA; ITALY; LARGE CELL LYMPHOMA; LOW DRUG DOSE; LYMPHOPROLIFERATIVE DISEASE; MANTLE CELL LYMPHOMA; MARGINAL ZONE LYMPHOMA; MEDICAL SOCIETY; MULTIPLE CYCLE TREATMENT; PRACTICE GUIDELINE; PRIORITY JOURNAL; T CELL LYMPHOMA;

EID: 84874568508     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mds517     Document Type: Article

References (126)

1. Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC 2008.
2. Alizadeh AA, Eisen MB, Davis RE et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503-511.
3. Rosenwald A, Wright G, Chan WC et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 1937-1947.
4. Hans CP, Weisenburger DD, Greiner TC et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: 275-282.
5. Gutiérrez-García G, Cardesa-Salzmann T, Climent F et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood 2011; 117: 4836-4843.
6. Salles G, de Jong D, Xie W et al. Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood 2011; 117: 7070-7078.
7. Aukema SM, Siebert R, Schuuring E et al. Double-hit B-cell lymphomas. Blood 2011; 117: 2319-2331.
8. Shipp MA, Harrington DP, Anderson JR et al. A predictive model for aggressive non-Hodgkins lymphoma. N Engl J Med 1993; 329: 987-994.
9. Sehn LH, Berry B, Chhanabhai M et al. The revised international prognostic index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2007; 109: 1857-1861.
10. Advani RH, Chen H, Habermann TM et al. Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol 2010; 151: 143-151.
11. Ziepert M, Hasenclever D, Kuhnt E et al. Standard international prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28: 2373-2380.
12. Pfreundschuh M, Trumper L, Osterborg A et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006; 7: 379-391.
13. Récher C, Coiffier B, Haioun C et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 2011; 378(9806): 1858-1867.
14. Cunningham D, Smith P, Mouncey P et al. R-CHOP14 versus R-CHOP21: result of a randomized phase III trial for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma. J Clin Oncol 2011; 29: 504s (abstr 8000).
15. Coiffier B, Gisselbrecht C, Herbrecht R et al. LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma. J Clin Oncol 1989; 7: 1018-1026.
16. Trumper L, Renner C, Nahler M et al. Intensification of CHOEP regimen for high-grade Non-Hodgkins-Lymphoma by G-CSF Feasibility of a 14-day regimen. Onkologie 1994; 17: 69-71.
17. Greb A, Bohlius J, Schiefer D et al. High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive Non-Hodgkin Lymphoma (NHL) in adults. Cochrane Database Syst Rev 2008; (1): CD004024.
18. Stiff PJ, Unger JM, Cook J et al. Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP {+/-} R for eight cycles to CHOP {+/-} R for six cycles followed by autotransplant for patients with highintermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). ASCO Meeting Abstracts 2011; 29: 8001.
19. Vitolo U, Chiappella A, Brusamolino E et al. A randomized multicentre phase III study for first line treatment of young patients with high risk (AAIPI 2-3) diffuse large B-cell lymphoma (DLBCL): rituximab (R) plus dose-dense chemotherapy CHOP14/MEGACHOP14 with or without intensified high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Results of DLCL04 trial of Italian Lymphoma Foundation (FIL). Ann Oncol 2011; 22: 106-106.
20. Schmitz N, Nickelsen M, Ziepert M et al. Conventional chemoimmunotherapy (R-CHOEP-14) or high-dose therapy (R-MEGA-CHOEP) for young, high-risk patients with aggressive B-cell lymphoma: final results of the randomized MEGA-CHOEP-Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Ann Oncol 2011; 22: 106-107.
21. Milpied N-J, Legouill S, Lamy T et al. No benefit of first-line rituximab (R)high-dose therapy (R-HDT) over R-CHOP14 for young adults with diffuse large B-cell lymphoma. preliminary results of the GOELAMS 075 prospective multicentre randomized trial. ASH Annual Meeting Abstracts 2010; 116: 685.
22. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235-242.
23. Habermann TM, Weller EA, Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006; 24: 3121-3127.
24. Pfreundschuh M, Schubert J, Ziepert M et al. Six versus eight cycles of biweekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008; 9: 105-116.
25. Tilly H, Lepage E, Coiffier B et al. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive nonHodgkin lymphoma. Blood 2003; 102: 4284-4289.
26. Delarue R, Tilly H, Salles G et al. R-CHOP14 Compared to R-CHOP21in elderly patients with diffuse large B-cell lymphoma(DLBCL): results of the second interim analysis of the LNH03-6B GELA study. Ann Oncol 2011; 22: 117-117.
27. Peyrade F, Jardin F, Thieblemont C et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol 2011; 12: 460-468.
28. Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive Non-Hodgkind? s lymphoma. N Engl J Med 1995; 333: 1540-1545.
29. Gisselbrecht C, Glass B, Mounier N et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28: 4184-4190.
30. Thieblemont C, Briere J, Mounier N et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol 2011; 29: 4079-4087.
31. Vellenga E, van Putten WLJ, van't Veer MB et al. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood 2008; 111: 537-543.
32. Crump M, Baetz T, Couban S et al. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer 2004; 101: 1835-1842.
33. Rigacci L, Fabbri A, Puccini B et al. Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. Cancer 2010; 116: 4573-4579.
34. van Kampen RJW, Canals C, Schouten HC et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell nonhodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European group for blood and marrow transplantation registry. J Clin Oncol 2011; 29: 1342-1348.
35. Thomson KJ, Morris EC, Bloor A et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-hodgkin's lymphoma. J Clin Oncol 2009; 27: 426-432.
36. Cheson BD, Pfistner B, Juweid ME et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007; 25(5): 579-586.
37. Juweid ME, Stroobants S, Hoekstra OS et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of international harmonization project in lymphoma. J Clin Oncol 2007; 25(5): 571-578.
38. Zijlstra J, Lindauer-van der Werf G, Hoekstra O et al. 18F-fluoro-deoxyglucose positron emission tomography for post-treatment evaluation of malignant lymphoma: a systematic review. Haematologica 2006; 91: 522-529.
39. Terasawa T, Nihashi T, Hotta T et al. 18F-FDG PET for posttherapy assessment of hodgkin's disease and aggressive non-hodgkin's lymphoma: a systematic review. J Nucl Med 2008; 49: 13-21.
40. Pregno P, Chiappella A, Belló M et al. The interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood 2012; 119(9): 2066-2073.
41. Horning SJ, Juweid ME, Schoder H et al. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood 2010; 115: 775-777.
42. Moskowitz CH, Schöder H, Teruya-Feldstein J et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-cell lymphoma. J Clin Oncol 2010; 28: 1896-1903.
43. Luigi Zinzani P, Stefoni V, Tani M et al. Role of [18F] fluorodeoxyglucose positron emission tomography scan in the follow-up of lymphoma. J Clin Oncol 2009; 27: 1781-1787.
44. Petersen PM, Gospodarowicz M, Tsang R et al. Long-term outcome in stage I and II follicular lymphoma following treatment with involved field radiation therapy alone. J Clin Oncol 2004; 22: 563.
45. Eich HT, Heinmann M, Stutzer H et al. Long term outcome and prognostic factors in early stage nodal low grade non-Hodgkins lymphomas treated with radiation therapy. Strahlenther Onkol 2009; 185: 288-229.
46. Lowry L, Smith P, Qian W et al. Reduced dose radiotherapy for local control in non Hodgkins lymphoma: a randomised Phase III trial. Radiother Oncol 2011; doi:10.1016/j.radonc.2011.05.013
47. Haas RL, Poortmans P, De Jong D et al. Effective palliation by low dose local radiotherapy for recurrent and/or chemotherapy refractory non-follicular lymphoma patients. Eur J Cancer 2005; 41: 1724-1730.
48. Seymour JF, Pro B, Fuller LM et al. Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma. J Clin Oncol 2003; 21: 2115-2122.
49. Advani R, Rosenberg SA, Horning SJ. Stage I and II follicular non-Hodgkin's lymphoma: long-term follow-up of no initial therapy. J Clin Oncol 2004; 22: 1454-1459.
50. Soubeyran P, Eghbali H, Trojani M et al. Is there any place for a wait-and-see policy in stage I0 follicular lymphoma? A study of 43 consecutive patients in a single center. Ann Oncol 1996; 7: 713-718.
51. Pugh TJ, Ballonoff A, Newman F et al. Improved survival in patients with low grade follicular lymphoma treated with radiation. Cancer 2010; 116: 3843-3851.
52. Ardeshna KM, Smith P, Norton A et al. British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 2003; 362: 516-522.
53. Brice P, Bastion Y, Lepage E et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Grouped'Etude des LymphomesFolliculaires. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 1997; 15: 1110-1117.
54. Young RC, Longo DL, Glatstein E, Jr et al. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Haematol 1988; 25: 11-16.
55. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med 1984; 311: 1471-1475.
56. Al-Tourah AJ, Gill KK, Chhanabhai M et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol 2008; 26: 5165-5169.
57. Hiddemann W, Kneba M, Dreyling M et al. Front-line therapy with Rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) significantly improves the outcome of patients with advanced stage follicular lymphomas as compared to CHOP alone-results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2005; 106: 3725-3732.
58. Herold M, Haas A, Srock S et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group hematology and oncology study. J Clin Oncol 2007; 25: 1986-1992.
59. Marcus R, Imrie K, Solal-Celigny P et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisolone alone in pateints with previously untreated advanced follicualr lymphoma. J Clin Oncol 2008; 28: 4579-4586.
60. Salles G, Mounier N, de Guibert S et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008; 112: 4824-4831.
61. Rummel MJ, Niederle N, Maschmeyer G et al. Bendamustin plus Ritxuiamb is superior in respect of progression free survival and CR rate when compared to CHOP plus Rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the STIL. Blood 2009; 110: 168-169.
62. Federico M, Luminari S, Dondi A et al. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced stage Follicular Lymphoma. Preliminary results of FOLL05 IIL trial. IX ICML Lugano, Switzerland, 15-18 June 2011. Ann Oncol 2011; 22(Suppl 4): 128.
63. Salles G, Seymour J-F, Offner F et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011; 377: 42-51.
64. Martinelli G, Schmitz SF, Utiger U et al. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol 2010; 28(29): 4480-4484.
65. Vidal L, Gafter-Gvili A, Leibovici L et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and metaanalysis of randomized trials. J Natl Cancer Inst 2009; 101(4): 248-255.
66. Morschhauser F, Redford J, Van Hoof A et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol 2008; 26: 5156-5164.
67. Lenz G, Dreyling M, Schiegnitz E et al. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood 2004; 104: 2667-2674.
68. Sebban C, Mounier N, Brousse N et al. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood 2006; 108: 2540-2544.
69. Gyan E, Foussard C, Bertrand P et al. High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood 2009; 113: 995-1001.
70. Ladetto M, De Marco F, Benedetti F et al. Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood 2008; 111(8): 4004-4013.
71. Schouten HC, Qian W, Kvaloy S et al. High-dose therapy improves progressionfree survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol 2003; 21: 3918-3927.
72. Montoto S, Canals C, Rohatiner AZ et al. Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study. Leukemia 2007; 21: 2324-2331.
73. Pettengell R, Schmitz N, Gisselbrecht C et al. Randomized study of rituximab in patients with relapsed or resistant follicular lymphoma prior to high-dose therapy as in vivo purging and to maintain remission following high-dose therapy. J Clin Oncol 2010; 28: 15s. [suppl; abstr 8005].
74. Sebban C, Brice P, Delarue R et al. Impact of rituximab and/or high-dose therapy with autotransplant at time of relapse in patients with follicular lymphoma: a GELA study. J Clin Oncol 2008; 26: 3614-3620.
75. Le Gouill S, De Guibert S, Planche L et al. Impact of the use of autologous stem cell transplantation at first relapse both in naive and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study. Haematologica 2011; 96(8): 1128-1135.
76. Weigert A, Uysal B, Metzner M et al. Impact of autologous stem cell transplantation and/or rituximab on outcome of patients with relapsed follicular lymphoma-retrospective analysis of 2 randomized trials of the German Low Grade Lymphoma Study Group (GLSG). Blood 2008; 112(11): 764 (Abstract 2189).
77. Ingram W, Devereux S, Das-Gupta EP et al. Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation in relapsed advanced stage follicular lymphoma. Br J Haematol 2008; 141: 235-243.
78. 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.
79. Eichhorst B, Dreyling M, Robak T et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011; 22(Suppl 6): vi50-vi54.
80. Dearden C. Disease-specific complications of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2008: 450-456.
81. Hodgson K, Ferrer G, Montserrat E et al. Chronic lymphocytic leukemia and autoimmunity: a systematic review. Haematologica 2011; 96(5): 752-761.
82. Hodgson K, Ferrer G, Pereira A et al. Autoimmune cytopenia in chronic lymphocytic leukaemia: diagnosis and treatment. Br J Haematol 2011; 154(1): 14-22.
83. Zent CS, Ding W, Reinalda MS et al. Autoimmune cytopenia in chronic lymphocytic leukemia/small lymphocytic lymphoma: changes in clinical presentation and prognosis. Leuk Lymphoma 2009; 50(8): 1261-1268.
84. Moreno C, Hodgson K, Ferrer G et al. Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. Blood 2010; 116(23): 4771-4776.
85. Strati P, Caligaris-Cappio F. A matter of debate in chronic lymphocytic leukemia (CLL): is the occurrence of autoimmune disorders an indicator of CLL therapy? Curr Opin Oncol 2011; 23(5): 455-460.
86. Zenz T, Mertens D, Küppers R et al. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010; 10(1): 37-50.
87. 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.
88. Hamblin TJ, Davis Z, Gardiner A et al. Unmutated IgV(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 1848-1854.
89. Döhner H, Stilgenbauer S, Benner A et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910-1916.
90. Kröber A, Seiler T, Benner A et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002; 100: 1410-1416.
91. Zenz T, Eichhorst B, Busch R et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol 2010; 28(29): 4473-4479.
92. 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.
93. 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): 975-980.
94. 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): 1164-1174.
95. 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: 3994-3901.
96. Dreger P, Döhner 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): 2438-2447.
97. Extermann M. Basic assessment of the older cancer patient. Curr Treat Options Oncol 2011; 12(3): 276-285.
98. Fischer K, Cramer P, Busch R et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicentre phase II trial of the German CLL Study Group. J Clin Oncol 2011; 10(26): 3559-3566.
99. Marotta G, Bigazzi C, Lenoci M et al. Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy. Haematologica 2000; 85(12): 1268-1270.
100. Bezares RF, Murro HH, Celebrin L et al. Fludarabine (F) administered on a three (F3a) alternate day-basis in selected CLL patients [abstract no. 53]. Leuk Lymphoma 2001; 42(Suppl 1).
101. Forconi F, Fabbri A, Lenoci M et al. Low-dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic leukaemia. Hematol Oncol 2008; 26(4):247-251.
102. Foon KA, Mehta D, Lentzsch S et al. Long-term results of chemoimmunotherapy with low-dose fludarabine, cyclophosphamide and highdose rituximab as initial treatment for patients with chronic lymphocytic leukemia. Blood 2012; 119(13): 3184-3185.
103. Eichhorst BF, Busch R, Stilgenbauer S et al. German CLL Study Group (GCLLSG): 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: 3382-3339.
104. Catovsky D, Richards S, Matutes E et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomized controlled trial. Lancet 2007; 370(9583): 230-239.
105. 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(24): 1750-1757.
106. Knauf WU, 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; 10(26): 4378-4384.
107. Hillmen P, Gribben JG, 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 ASH Annual Meeting Abstracts 2009; 114: 3428.
108. Foa R, Cioli S, DiRaimondo F et al. A phase II study of chlorambucil plus rituximab followed by maintenance versus observation in elderly patients with previously untreated chronic lymphocytic leukemia: results of the first interim analysis. ASH Annual Meeting Abstracts 2010; 116: 2462.
109. 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: 5616-5623.
110. Wierda WG, Padmanabhan S, Chan GW et al. Hx-CD20-406 Study Investigators. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood 2011; 118(19): 5126-5129.
111. 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.
112. Wierda WG, Kipps TJ, Durig J et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood 2011; 117: 6450-6458.
113. 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 trial of the GCLLSG. J Clin Oncol 2009; 27: 3994-4001.
114. Lanasa MC, Andritsos L, Brown JR et al. Interim analysis of EFC6663, a multicenter phase 2 study of alvocidib (flavopiridol), demonstrates clinical responses among patients with fludarabine refractory CLL. ASH Annual Meeting Abstracts 2010; 116: 58.
115. Badoux XC, Keating MJ, Wen S et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood 2011; 117(11): 3016-3024.
116. 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.
117. Gonzalez D, Martinez P, Wade R et al. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J Clin Oncol 2011; 92(16): 2223-2229.
118. Pospisilova S, Gonzalez D, Malcikova J et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia 2012. doi: 10.1038/leu.2012.25. [Epub ahead of print]
119. 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. Blood (ASH Annual Meeting Abstracts) 2010; 116: 2357.
120. Stilgenbauer S, Zenz Th. Understanding and managing ultra-high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2010; 481-488.
121. Keating MJ, Wierda WG, Tam CS et al. Long term outcome following treatment failure of FCR chemoimmunotherapy as initial therapy for chronic lymphocytic leukemia [Abstract]. Blood 2009; 114(22): 2381-2388.
122. 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: 3016-3024.
123. 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 ClinOncol 2008; 26: 4912-4920.
124. Khouri IF, Bassett R, Poindexter N et al. Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome. Cancer 2011; 117: 4679-4688.
125. Caballero D, Garcia-Marco JA, Martino R et al. Allogeneic Transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities. Clin Cancer Res 2005; 11: 7757-7763.
126. Farina L, Carniti C, Dodero A et al. Qualitative and quantitative polymerase chain reaction monitoring of minimal residual disease in relapsed chronic lymphocytic leukemia: early assessment can predict long-term outcome after reduced intensity allogeneic transplantation. Haematologica 2009; 94: 654-662.