Using biologic predictive factors to direct therapy of diffuse large B-cell lymphoma

Therapeutic Advances in Hematology

Volumn 4, Issue 1, 2013, Pages 43-57

  Dunleavy, Kieron ^a   Grant, Cliona ^a   Wilson, Wyndham H ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

B cell receptor signaling; diffuse large B cell lymphoma; gene expression profiling; germinal center; molecular subtypes; mutational analysis; nuclear factor kappa B

Indexed keywords

B LYMPHOCYTE RECEPTOR; BORTEZOMIB; CYCLOPHOSPHAMIDE; DNA TOPOISOMERASE (ATP HYDROLYSING); DOXORUBICIN; ETOPOSIDE; EVEROLIMUS; FOSTAMATINIB; IBRUTINIB; IDELALISIB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1; JANUS KINASE; LENALIDOMIDE; MYC PROTEIN; MYELOID DIFFERENTIATION FACTOR 88; PREDNISOLONE; PROTEIN BCL 2; PROTEIN BCL 6; RITUXIMAB; RUXOLITINIB; TEMSIROLIMUS; VINCRISTINE;

B CELL LYMPHOMA; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; B LYMPHOCYTE DIFFERENTIATION; CANCER CLASSIFICATION; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER PROGNOSIS; CANCER RECURRENCE; CANCER RESISTANCE; CANCER SURVIVAL; DRUG TREATMENT FAILURE; ENZYME INHIBITION; GENE EXPRESSION PROFILING; GENE MUTATION; GERMINAL CENTER; HODGKIN DISEASE; HUMAN; INTERNATIONAL PROGNOSTIC INDEX; LARGE CELL LYMPHOMA; LYMPHOCYTE ACTIVATION; LYMPHOCYTE PROLIFERATION; LYMPHOMA; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; NODULAR SCLEROSIS HODGKIN LYMPHOMA; NONHODGKIN LYMPHOMA; OVERALL SURVIVAL; PREDICTOR VARIABLE; PRIMARY MEDIASTINAL B CELL LYMPHOMA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; TREATMENT OUTCOME; TREATMENT RESPONSE;

EID: 84993734721     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620712464508     Document Type: Article

References (86)

1. Abou-Elella A. Weisenburger D. Vose J. Kollath J. Lynch J. Bast M. et al. (1999) Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group. J Clin Oncol 17: 784–790.
2. Abramson J. Hellmann M. Feng Y. Barnes J. Takvorian T. Toomey C. et al. (2011) High rate of initial treatment failure in patients with primary mediastinal B-cell lymphoma treated with R-CHOP. Blood ASH Annual Meeting Abstracts 118: 1601.
3. Alizadeh A. Eisen M. Davis R. Ma C. Lossos I. Rosenwald A. et al. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403: 503–511.
4. Allen C. Saigal K. Nottingham L. Arun P. Chen Z. van Waes C. (2008) Bortezomib-induced apoptosis with limited clinical response is accompanied by inhibition of canonical but not alternative nuclear factor-{kappa}B subunits in head and neck cancer. Clin Cancer Res 14: 4175–4185.
5. Aviles A. Neri N. Fernandez R. Huerta-Guzman J. Nambo M. (2012) Randomized clinical trial to assess the efficacy of radiotherapy in primary mediastinal large B-lymphoma. Int J Radiat Oncol Biol Phys 83: 1227–1231.
6. Castellino S. Geiger A. Mertens A. Leisenring W. Tooze J. Goodman P. et al. (2011) Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 117: 1806–1816.
7. Cerchietti L. Ghetu A. Zhu X. Da Silva G. Zhong S. Matthews M. et al. (2010) A small-molecule inhibitor of BCL 6 kills DLBCL cells in vitro and in vivo. Cancer Cell 17: 400–411.
8. Choi W. Weisenburger D. Greiner T. Piris M. Banham A. Delabie J. et al. (2009) A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 15: 5494–5502.
9. Dalla-Favera R. Migliazza A. Chang C. Niu H. Pasqualucci L. Butler M. et al. (1999) Molecular pathogenesis of B cell malignancy: the role of BCL-6. Curr Top Microbiol Immunol 246: 257–263; discussion 263-255.
10. Davis R. Brown K. Siebenlist U. Staudt L. (2001) Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 194: 1861–1874.
11. Davis R. Ngo V. Lenz G. Tolar P. Young R. Romesser P. et al. (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463: 88–92.
12. Diehl V. Franklin J. Pfreundschuh M. Lathan B. Paulus U. Hasenclever D. et al. (2003) Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 348: 2386–2395.
13. Dunleavy K. Bollard C. (2011) Sobering realities of surviving Hodgkin lymphoma. Blood 117: 1772–1773.
14. Dunleavy K. Janik J. Gea-Banacloche J. Shovlin M. White T. Goldschmidt N. et al. (2004) Phase I / II study of bortezomib alone and bortezomib with dose-adjusted EPOCH chemotherapy in relapsed or refractory aggressive B-cell lymphoma. ASH Annual Meeting Abstracts 104: 1385.
15. Dunleavy K. Little R. Pittaluga S. Grant N. Wayne A. Carrasquillo J. et al. (2010) The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood 115: 3017–3024.
16. Dunleavy K. Pittaluga S. Czuczman M. Dave S. Wright G. Grant N. et al. (2009) Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood 113: 6069–6076.
17. Dunleavy K. Pittaluga S. Janik J. Grant N. Shovlin M. Steinberg S. et al. (2006) Primary mediastinal large B-cell lymphoma (PMBL) may be significantly improved by the addition of rituximab to dose-adjusted EPOCH and obviates the need for radiation: results from a prospective study of 44 patients. Blood (ASH Annual Meeting Abstracts) 108: 209.
18. Dunleavy K. Pittaluga S. Shovlin M. Grant N. Grant C. Chen C. et al. (2011 a) Untreated primary mediastinal B-cell (PMBL) and mediastinal grey zone (MGZL) lymphomas: comparison of biological features and clinical outcome following DA-EPOCH-R without radiation. Ann Oncol 22 (4): abstract 149. 2011.
19. Dunleavy K. Pittaluga S. Wayne A. Shovlin M. Johnson J. Little R. et al. (2011 b) MYC + Aggressive B-cell lymphomas: novel therapy of untreated Burkitt lymphoma (BL) and MYC + diffuse large B-cell lymphoma (DLBCL) with DA-EPOCH-R. Ann Oncol 22(Suppl. 4): abstract 071.
20. Dunleavy K. Wilson W.H. (2011) Differential role of BCL 2 in molecular subtypes of diffuse large B-cell lymphoma. Clin Cancer Res 17: 7505–7507.
21. Flinn I. Byrd J. Furman R. Brown J. Benson D. Coutre S. et al. (2009) Evidence of clinical activity in a phase 1 study of CAL-101, an oral P 110 delta isoform-selective inhibitor of phosphatidylinositol 3-kinase in patients with relapsed or refractory B-cell malignancies. Blood (ASH Annual Meeting Abstracts) 114: abstract 922.
22. Friedberg J. Sharman J. Sweetenham J. Johnston P. Vose J. Lacasce A. et al. (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 115: 2578–2585.
23. Gascoyne R. Adomat S. Krajewski S. Krajewska M. Horsman D. Tolcher A. et al. (1997) Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. Blood 90: 244–251.
24. Gonzalez C. Medeiros L. Jaffe E. (1991) Composite lymphoma. A clinicopathologic analysis of nine patients with Hodgkin's disease and B-cell non-Hodgkin's lymphoma. Am J Clin Pathol 96: 81–89.
25. Gutierrez-Garcia G. Cardesa-Salzmann T. Climent F. Gonzalez-Barca E. Mercadal S. Mate J. et al. (2011) Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood 117: 4836–4843.
26. Hans C. Weisenburger D. Greiner T. Gascoyne R. Delabie J. Ott G. et al. (2003) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103: 275–282.
27. Harris N. Jaffe E. Stein H. Banks P. Chan J. Cleary M. et al. (1994) A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84: 1361–1392.
28. Hernandez-Ilizaliturri F. Deeb G. Zinzani P. Pileri S. Malik F. Macon W. et al. (2011) Higher response to lenalidomide in relapsed / refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer 117: 5058–5066.
29. Hernandez-Ilizaliturri F.J. Reddy N. Holkova B. Ottman E. Czuczman M. (2005) Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res 11: 5984–5992.
30. Houldsworth J. Petlakh M. Olshen A. Chaganti R. (2008) Pathway activation in large B-cell non-Hodgkin lymphoma cell lines by doxorubicin reveals prognostic markers of in vivo response. Leuk Lymphoma 49: 2170–2180.
31. Iqbal J. Meyer P. Smith L. Johnson N. Vose J. Greiner T. et al. (2011) BCL 2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res 17: 7785–7795.
32. Jaffe E. (2009) The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program: 523–531.
33. Jaffe E. Harris N. Stein H. Vardiman J. (2001) Tumours of haematopoietic and lymphoid tissues, In: World Health Organization Classification of Tumours, 1st edn. Lyon: IARC Press, p. 351.
34. Klapper W. Stoecklein H. Zeynalova S. Ott G. Kosari F. Rosenwald A. et al. (2008) Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Leukemia 22: 2226–2229.
35. Kurosu T. Fukuda T. Miki T. Miura O. (2003) BCL 6 overexpression prevents increase in reactive oxygen species and inhibits apoptosis induced by chemotherapeutic reagents in B-cell lymphoma cells. Oncogene 22: 4459–4468.
36. Lenz G. Davis R. Ngo V. Lam L. George T. Wright G. et al. (2008 a) Oncogenic CARD 11 mutations in human diffuse large B cell lymphoma. Science 319: 1676–1679.
37. Lenz G. Wright G. Emre N. Kohlhammer H. Dave S. Davis R. et al. (2008 b) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 105: 13520–13525.
38. Matsuyama T. Grossman A. Mittrucker H. Siderovski D. Kiefer F. Kawakami T. et al. (1995) Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nucleic Acids Res 23: 2127–2136.
39. Mittrucker H. Matsuyama T. Grossman A. Kundig T. Potter J. Shahinian A. et al. (1997) Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275: 540–543.
40. National Cancer Institute (1982) National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 49: 2112–2135.
41. Ngo V. Davis R. Lamy L. Yu X. Zhao H. Lenz G. et al. (2006) A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441: 106–110.
42. Ngo V. Young R. Schmitz R. Jhavar S. Xiao W. Lim K. et al. (2010) Oncogenically active MYD 88 mutations in human lymphoma. Nature 470: 115–119.
43. O'Reilly S. Hoskins P. Klimo P. Connors J. (1991) MACOP-B and VACOP-B in diffuse large cell lymphomas and MOPP / ABV in Hodgkin's disease. Ann Oncol 2(Suppl. 1): 17–23.
44. Orlowski R. Baldwin A. (2002) NF-kappaB as a therapeutic target in cancer. Trends Mol Med 8: 385–389.
45. Orlowski R. Kuhn D. (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res 14: 1649–1657.
46. Paik J. Jeon Y. Park S. Kim Y. Kim J. Huh J. et al. (2005) Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non-germinal centre B-like diffuse large B-cell lymphomas. Histopathology 47: 281–291.
47. Parekh S. Polo J. Shaknovich R. Juszczynski P. Lev P. Ranuncolo S. et al. (2007) BCL 6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood 110: 2067–2074.
48. Parekh S. Prive G. Melnick A. (2008) Therapeutic targeting of the BCL 6 oncogene for diffuse large B-cell lymphomas. Leuk Lymphoma 49: 874–882.
49. Pasqualucci L. Migliazza A. Basso K. Houldsworth J. Chaganti R. Dalla-Favera R. (2003) Mutations of the BCL 6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood 101: 2914–2923.
50. Pfreundschuh M. Trumper L. Kloess M. Schmits R. Feller A. Rube C. et al. (2004 a) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104: 634–641.
51. Pfreundschuh M. Trumper L. Kloess M. Schmits R. Feller A. Rudolph C. et al. (2004 b) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood 104: 626–633.
52. Pfreundschuh M. Trumper L. Osterborg A. Pettengell R. Trneny M. Imrie K. et al. (2006) 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 7: 379–391.
53. Phan R. Dalla-Favera R. (2004) The BCL 6 proto-oncogene suppresses p 53 expression in germinal-centre B cells. Nature 432: 635–639.
54. Phan R. Saito M. Basso K. Niu H. Dalla-Favera R. (2005) BCL 6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p 21 and cell cycle arrest in germinal center B cells. Nat Immunol 6: 1054–1060.
55. Quintas-Cardama A. Kantarjian H. Cortes J. Verstovsek S. (2011) Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov 10: 127–140.
56. Ranuncolo S. Polo J. Dierov J. Singer M. Kuo T. Greally J. et al. (2007) Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR. Nat Immunol 8: 705–714.
57. Reddy N. Hernandez-Ilizaliturri F. Deeb G. Roth M. Vaughn M. Knight J. et al. (2008) Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol 140: 36–45.
58. Rosenwald A. Wright G. Chan W. Connors J. Campo E. Fisher R. et al. (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346: 1937–1947.
59. Rosenwald A. Wright G. Leroy K. Yu X. Gaulard P. Gascoyne R. et al. (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 198: 851–862.
60. Ruan J. Martin P. Furman R. Lee S. Cheung K. Vose J. et al. (2010) Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 29: 690–697.
61. Rui L. Emre N. Kruhlak M. Chung H. Steidl C. Slack G. et al. (2010) Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell 18: 590–605.
62. Savage K. Al-Rajhi N. Voss N. Paltiel C. Klasa R. Gascoyne R. et al. (2006) Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 17: 123–130.
63. Savage K. Johnson N. Ben-Neriah S. Connors J. Sehn L. Farinha P. et al. (2009) MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 114: 3533–3537.
64. Savage K. Monti S. Kutok J. Cattoretti G. Neuberg D. de Leval L. et al. (2003) The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin's lymphoma. Blood 102: 3871–3879.
65. Shaffer A. Rosenwald A. Staudt L. (2002) Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2: 920–932.
66. Siu W. Lau A. Arooz T. Chow J. Ho H. Poon R. (2004) Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms. Mol Cancer Ther 3: 621–632.
67. Smith S. van Besien K. Karrison T. Dancey J. McLaughlin P. Younes A. et al. (2010) Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol 28: 4740–4746.
68. Stansfeld A. Diebold J. Noel H. Kapanci Y. Rilke F. Kelenyi G. et al. (1988) Updated Kiel classification for lymphomas. Lancet 1: 292–293.
69. Staudt L. Dunleavy K. Buggy J. Hedrick E. Lucas N. Pittaluga S. et al. (2011) The Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 modulates chronic active BCR signaling and induces tumor regression in relapsed / refractory ABC DLBCL. Blood (ASH Annual Meeting Abstracts) 118: abstract 2716.
70. Strauss S. Higginbottom K. Juliger S. Maharaj L. Allen P. Schenkein D. et al. (2007) The proteasome inhibitor bortezomib acts independently of p 53 and induces cell death via apoptosis and mitotic catastrophe in B-cell lymphoma cell lines. Cancer Res 67: 2783–2790.
71. Tay K. Dunleavy K. Wilson W. (2010) Novel agents for B-cell non-Hodgkin lymphoma: science and the promise. Blood Rev 24 (2): 69–82.
72. The International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 329: 987–994.
73. Theard D. Coisy M. Ducommun B. Concannon P. Darbon J. (2001) Etoposide and adriamycin but not genistein can activate the checkpoint kinase Chk 2 independently of ATM/ATR. Biochem Biophys Res Commun 289: 1199–1204.
74. Todeschini G. Secchi S. Morra E. Vitolo U. Orlandi E. Pasini F. et al. (2004) Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer 90: 372–376.
75. Tschopp J. Irmler M. Thome M. (1998) Inhibition of fas death signals by FLIPs. Curr Opin Immunol 10: 552–558.
76. Verstovsek S. Kantarjian H. Mesa R. Pardanani A. Cortes-Franco J. Thomas D. et al. (2010) Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 363: 1117–1127.
77. Wiestner A. Staudt L. (2003) Towards a molecular diagnosis and targeted therapy of lymphoid malignancies. Semin Hematol 40: 296–307.
78. Wilson W. Dunleavy K. Pittaluga S. Grant N. Steinberg S. Raffeld M. et al. (2004) Dose-adjusted EPOCH-rituximab is highly effective in the GCB and ABC subtypes of untreated diffuse large B-cell lymphoma. ASH Annual Meeting Abstracts 104: 159.
79. Wilson W. Grossbard M. Pittaluga S. Cole D. Pearson D. Drbohlav N. et al. (2002) Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood 99: 2685–2693.
80. Wilson W. Hernandez-Ilizaliturri F. Dunleavy K. Little R. O'Connor O. (2010 a) Novel disease targets and management approaches for diffuse large B-cell lymphoma. Leuk Lymphoma 51(Suppl. 1): 1–10.
81. Wilson W. Jung S. Porcu P. Hurd D. Johnson J. Martin S. et al. (2011) A cancer and leukemia group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica 97: 758–765.
82. Wilson W. O'Connor O. Czuczman M. LaCasce A. Gerecitano J. Leonard J. et al. (2010 b) Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol 11: 1149–1159.
83. Wilson W. Teruya-Feldstein J. Fest T. Harris C. Steinberg S. Jaffe E. et al. (1997) Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood 89: 601–609.
84. Witzig T. Geyer S. Ghobrial I. Inwards D. Fonseca R. Kurtin P. et al. (2005) Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23: 5347–5356.
85. Zinzani P. Martelli M. Bertini M. Gianni A. Devizzi L. Federico M. et al. (2002) Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica 87: 1258–1264.
86. Zinzani P. Martelli M. Magagnoli M. Pescarmona E. Scaramucci L. Palombi F. et al. (1999) Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients. Blood 94: 3289–3293.