Annals of Hematology

, Volume 92, Issue 9, pp 1151–1179

Clinical practice guidelines for diagnosis, treatment, and follow-up of patients with mantle cell lymphoma. Recommendations from the GEL/TAMO Spanish Cooperative Group

  • Dolores Caballero
  • Elías Campo
  • Armando López-Guillermo
  • Alejandro Martín
  • Reyes Arranz-Sáez
  • Eva Giné
  • Andrés López
  • Eva González-Barca
  • Miguel Ángel Canales
  • Marcos González-Díaz
  • Alberto Orfao
Review Article


Mantle cell lymphoma (MCL) is considered a distinct type of B-cell lymphoma genetically characterized by the t(11;14) translocation and cyclin D1 overexpression. There is also a small subset of tumors negative for cyclin D1 expression that are morphologically and immunophenotypically indistinguishable from conventional MCL. Although in the last decades, the median overall survival of patients with MCL has improved significantly, it is still considered as one of the poorest prognoses diseases among B-cell lymphomas. Election of treatment for patients with MCL is complex due to the scarcity of solid evidence. Current available data shows that conventional chemotherapy does not yield satisfactory results as in other types of B-cell lymphomas. However, the role of other approaches such as autologous or allogenic stem cell transplantation, immunotherapy, the administration of consolidation or maintenance schedules, or the use of targeted therapies still lack clear indications. In view of this situation, the Spanish Group of Lymphomas/Autologous Bone Marrow Transplantation has conducted a series of reviews on different aspects of MCL, namely its diagnosis, prognosis, first-line and salvage treatment (both in young and elderly patients), new targeted therapies, and detection of minimal residual disease. On the basis of the available evidence, a series of recommendations have been issued with the intention of providing guidance to clinicians on the diagnosis, treatment, and monitoring of patients with MCL.


Stem cell transplantation Cyclin D1 Cytarabine Immunochemotherapy Ki-67 Maintenance therapy Mantle cell lymphoma Minimal residual disease Prognostic factors Proliferation index Salvage therapy 


  1. 1.
    Weisenburger DD, Kim H, Rappaport H (1982) Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma. Cancer 49(7):1429–1438PubMedCrossRefGoogle Scholar
  2. 2.
    Zhou Y, Wang H, Fang W, Romaguer JE, Zhang Y, Delasalle KB, Kwak L, Yi Q et al (2008) Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 113(4):791–798PubMedCrossRefGoogle Scholar
  3. 3.
    Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P, Reiser M, Forstpointner R et al (2009) Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol 27(4):511–518PubMedCrossRefGoogle Scholar
  4. 4.
    U.S. Preventive Services Task Force. Definitions of levels of evidence and grades of recommendation. and Accessed July 2011.
  5. 5.
    Jares P, Colomer D, Campo E (2007) Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer 7(10):750–762PubMedCrossRefGoogle Scholar
  6. 6.
    Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM et al (2003) The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 3(2):185–197PubMedCrossRefGoogle Scholar
  7. 7.
    Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, Valera A, Song JY, Woroniecka R et al (2012) CCND2 rearrangements are the most frequent genetic events in cyclin D1-negative mantle cell lymphoma. Blood 121(8):1394–1402PubMedCrossRefGoogle Scholar
  8. 8.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haemotopoietic and lymphoid tissues, 4th edn. WHO Press, Geneva (Switzerland)Google Scholar
  9. 9.
    Meusers P, Hense J, Brittinger G (1997) Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems. Leukemia 11(Suppl 2):S60–S64PubMedGoogle Scholar
  10. 10.
    Pileri SA, Falini B (2009) Mantle cell lymphoma. Haematologica 94(11):1488–1492PubMedCrossRefGoogle Scholar
  11. 11.
    Ferrer A, Salaverria I, Bosch F, Villamor N, Rozman M, Bea S, Gine E, Lopez-Guillermo A et al (2007) Leukemic involvement is a common feature in mantle cell lymphoma. Cancer 109(12):2473–2480PubMedCrossRefGoogle Scholar
  12. 12.
    Tiemann M, Schrader C, Klapper W, Dreyling MH, Campo E, Norton A, Berger F, Kluin P et al (2005) Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol 131(1):29–38PubMedCrossRefGoogle Scholar
  13. 13.
    Majlis A, Pugh WC, Rodriguez MA, Benedict WF, Cabanillas F (1997) Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants. J Clin Oncol 15(4):1664–1671PubMedGoogle Scholar
  14. 14.
    Orchard J, Garand R, Davis Z, Babbage G, Sahota S, Matutes E, Catovsky D, Thomas PW et al (2003) A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease. Blood 101(12):4975–4981PubMedCrossRefGoogle Scholar
  15. 15.
    Angelopoulou MK, Siakantariz MP, Vassilakopoulos TP, Kontopidou FN, Rassidakis GZ, Dimopoulou MN, Kittas C, Pangalis GA (2002) The splenic form of mantle cell lymphoma. Eur J Haematol 68(1):12–21PubMedCrossRefGoogle Scholar
  16. 16.
    Matutes E, Parry-Jones N, Brito-Babapulle V, Wotherspoon A, Morilla R, Atkinson S, Elnenaei MO, Jain P et al (2004) The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients. Leuk Lymphoma 45(10):2007–2015PubMedCrossRefGoogle Scholar
  17. 17.
    Cheuk W, Wong KO, Wong CS, Chan JK (2004) Consistent immunostaining for cyclin D1 can be achieved on a routine basis using a newly available rabbit monoclonal antibody. Am J Surg Pathol 28(6):801–807PubMedCrossRefGoogle Scholar
  18. 18.
    Remstein ED, Kurtin PJ, Buno I, Bailey RJ, Proffitt J, Wyatt WA, Hanson CA, Dewald GW (2000) Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma. Br J Haematol 110(4):856–862PubMedCrossRefGoogle Scholar
  19. 19.
    Gerdes J, Dallenbach F, Lennert K, Lemke H, Stein H (1984) Growth fractions in malignant non-Hodgkin’s lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67. Hematol Oncol 2(4):365–371PubMedCrossRefGoogle Scholar
  20. 20.
    Rule SA, Poplar S, Evans PA, O’Connor SJ, Owen RG (2011) Indolent mantle-cell lymphoma: immunoglobulin variable region heavy chain sequence analysis reveals evidence of disease 10 years prior to symptomatic clinical presentation. J Clin Oncol 29(15):e437–e439PubMedCrossRefGoogle Scholar
  21. 21.
    Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M et al (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111(2):558–565PubMedCrossRefGoogle Scholar
  22. 22.
    de Jong D, Rosenwald A, Chhanabhai M, Gaulard P, Klapper W, Lee A, Sander B, Thorns C et al (2007) Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications—a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol 25(7):805–812PubMedCrossRefGoogle Scholar
  23. 23.
    Klapper W, Hoster E, Determann O, Oschlies I, van der Laak J, Berger F, Bernd HW, Cabecadas J et al (2009) Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network. J Hematop 2(2):103–111PubMedCrossRefGoogle Scholar
  24. 24.
    Yatabe Y, Suzuki R, Tobinai K, Matsuno Y, Ichinohasama R, Okamoto M, Yamaguchi M, Tamaru J et al (2000) Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma. Blood 95(7):2253–2261PubMedGoogle Scholar
  25. 25.
    Bea S, Campo E (2008) Secondary genomic alterations in non-Hodgkin’s lymphomas: tumor-specific profiles with impact on clinical behavior. Haematologica 93(5):641–645PubMedCrossRefGoogle Scholar
  26. 26.
    Mozos A, Royo C, Hartmann E, De Jong D, Baro C, Valera A, Fu K, Weisenburger DD et al (2009) SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica 94(11):1555–1562PubMedCrossRefGoogle Scholar
  27. 27.
    Ek S, Dictor M, Jerkeman M, Jirstrom K, Borrebaeck CA (2008) Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma. Blood 111(2):800–805PubMedCrossRefGoogle Scholar
  28. 28.
    Martin P, Chadburn A, Christos P, Weil K, Furman RR, Ruan J, Elstrom R, Niesvizky R et al (2009) Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol 27(8):1209–1213PubMedCrossRefGoogle Scholar
  29. 29.
    Fernàndez V, Salamero O, Espinet B, Solé F, Royo C, Navarro A, Camacho F, Bea S et al (2010) Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res 70(4):1408–1418PubMedCrossRefGoogle Scholar
  30. 30.
    Navarro A, Clot G, Royo C, Jares P, Hadzidimitriou A, Agathangelidis A, Bikos V, Darzentas N et al (2012) Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features. Cancer Res 72(20):5307–5316PubMedCrossRefGoogle Scholar
  31. 31.
    Ondrejka SL, Lai R, Kumar N, Smith SD, Hsi ED (2011) Indolent mantle cell leukemia: clinicopathologic variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis. Haematologica 96(8):1121–1127PubMedCrossRefGoogle Scholar
  32. 32.
    Royo C, Navarro A, Clot G, Salaverria I, Gine E, Jares P, Colomer D, Wiestner A et al (2012) Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease. Leuk Off Journal Leuk Soc Am Leuk Res Fund UK 26(8):1895–1898CrossRefGoogle Scholar
  33. 33.
    Nygren L, Baumgartner Wennerholm S, Klimkowska M, Christensson B, Kimby E, Sander B (2012) Prognostic role of SOX11 in a population-based cohort of mantle cell lymphoma. Blood 119(18):4215–4223PubMedCrossRefGoogle Scholar
  34. 34.
    Wang X, Asplund AC, Porwit A, Flygare J, Smith CI, Christensson B, Sander B (2008) The subcellular Sox11 distribution pattern identifies subsets of mantle cell lymphoma: correlation to overall survival. Br J Haematol 143(2):248–252PubMedCrossRefGoogle Scholar
  35. 35.
    Carvajal-Cuenca A, Sua LF, Silva NM, Pittaluga S, Royo C, Song JY, Sargent RL, Espinet B et al (2012) In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior. Haematologica 97(2):270–278PubMedCrossRefGoogle Scholar
  36. 36.
    Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (2011) The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 117(19):5019–5032PubMedCrossRefGoogle Scholar
  37. 37.
    Zucca E, Roggero E, Pinotti G, Pedrinis E, Cappella C, Venco A, Cavalli F (1995) Patterns of survival in mantle cell lymphoma. Ann Oncol 6(3):257–262PubMedGoogle Scholar
  38. 38.
    Bosch F, Lopez-Guillermo A, Campo E, Ribera JM, Conde E, Piris MA, Vallespi T, Woessner S et al (1998) Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors. Cancer 82(3):567–575PubMedCrossRefGoogle Scholar
  39. 39.
    Weisenburger DD, Vose JM, Greiner TC, Lynch JC, Chan WC, Bierman PJ, Dave BJ, Sanger WG et al (2000) Mantle cell lymphoma. A clinicopathologic study of 68 cases from the Nebraska Lymphoma Study Group. Am J Hematol 64(3):190–196PubMedCrossRefGoogle Scholar
  40. 40.
    Parrens M, Belaud-Rotureau MA, Fitoussi O, Carerre N, Bouabdallah K, Marit G, Dubus P, de Mascarel A et al (2006) Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features. Histopathology 48(4):353–362PubMedCrossRefGoogle Scholar
  41. 41.
    Bernard M, Gressin R, Lefrere F, Drenou B, Branger B, Caulet-Maugendre S, Tass P, Brousse N et al (2001) Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. Leukemia 15(11):1785–1791PubMedCrossRefGoogle Scholar
  42. 42.
    Räty R, Franssila K, Joensuu H, Teerenhovi L, Elonen E (2002) Ki-67 expression level, histological subtype, and the International Prognostic Index as outcome predictors in mantle cell lymphoma. Eur J Haematol 69(1):11–20PubMedCrossRefGoogle Scholar
  43. 43.
    Hernandez L, Fest T, Cazorla M, Teruya-Feldstein J, Bosch F, Peinado MA, Piris MA, Montserrat E et al (1996) p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas. Blood 87(8):3351–3359PubMedGoogle Scholar
  44. 44.
    Louie DC, Offit K, Jaslow R, Parsa NZ, Murty VV, Schluger A, Chaganti RS (1995) p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32). Blood 86(8):2892–2899PubMedGoogle Scholar
  45. 45.
    Stefancikova L, Moulis M, Fabian P, Ravcukova B, Vasova I, Muzik J, Malcikova J, Falkova I et al (2010) Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma. Int J Oncol 36(3):699–706PubMedGoogle Scholar
  46. 46.
    Parry-Jones N, Matutes E, Morilla R, Brito-Babapulle V, Wotherspoon A, Swansbury GJ, Catovsky D (2007) Cytogenetic abnormalities additional to t(11;14) correlate with clinical features in leukaemic presentation of mantle cell lymphoma, and may influence prognosis: a study of 60 cases by FISH. Br J Haematol 137(2):117–124PubMedCrossRefGoogle Scholar
  47. 47.
    Beà S, Ribas M, Hernandez JM, Bosch F, Pinyol M, Hernandez L, Garcia JL, Flores T et al (1999) Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants. Blood 93(12):4365–4374PubMedGoogle Scholar
  48. 48.
    Espinet B, Salaverria I, Bea S, Ruiz-Xiville N, Balague O, Salido M, Costa D, Carreras J et al (2010) Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma. Genes Chromosomes Cancer 49(5):439–451PubMedGoogle Scholar
  49. 49.
    Salaverria I, Zettl A, Bea S, Moreno V, Valls J, Hartmann E, Ott G, Wright G et al (2007) Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature. J Clin Oncol 25(10):1216–1222PubMedCrossRefGoogle Scholar
  50. 50.
    Andersen NS, Jensen MK, de Nully BP, Geisler CH (2002) A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors. Eur J Cancer 38(3):401–408PubMedCrossRefGoogle Scholar
  51. 51.
    Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD (1997) Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood 89(6):2067–2078PubMedGoogle Scholar
  52. 52.
    Oinonen R, Franssila K, Teerenhovi L, Lappalainen K, Elonen E (1998) Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients. Eur J Cancer 34(3):329–336PubMedCrossRefGoogle Scholar
  53. 53.
    Samaha H, Dumontet C, Ketterer N, Moullet I, Thieblemont C, Bouafia F, Callet-Bauchu E, Felman P et al (1998) Mantle cell lymphoma: a retrospective study of 121 cases. Leukemia 12(8):1281–1287PubMedCrossRefGoogle Scholar
  54. 54.
    Geisler CH, Kolstad A, Laurell A, Raty R, Jerkeman M, Eriksson M, Nordstrom M, Kimby E et al (2010) The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT). Blood 115(8):1530–1533PubMedCrossRefGoogle Scholar
  55. 55.
    van de Schans SA, Janssen-Heijnen ML, Nijziel MR, Steyerberg EW, van Spronsen DJ (2010) Validation, revision and extension of the Mantle Cell Lymphoma International Prognostic Index in a population-based setting. Haematologica 95(9):1503–1509PubMedCrossRefGoogle Scholar
  56. 56.
    Ghielmini M, Zucca E (2009) How I treat mantle cell lymphoma. Blood 114(8):1469–1476PubMedCrossRefGoogle Scholar
  57. 57.
    Dreyling M, Hiddemann W, for The European MCLN (2009) Current treatment standards and emerging strategies in mantle cell lymphoma. Hematology 2009(1):542–551CrossRefGoogle Scholar
  58. 58.
    Leitch HA, Gascoyne RD, Chhanabhai M, Voss NJ, Klasa R, Connors JM (2003) Limited-stage mantle-cell lymphoma. Ann Oncol 14(10):1555–1561PubMedCrossRefGoogle Scholar
  59. 59.
    Martin P, Chadburn A, Christos P, Furman R, Ruan J, Joyce MA, Fusco E, Glynn P et al (2008) Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies. Ann Oncol 19(7):1327–1330PubMedCrossRefGoogle Scholar
  60. 60.
    Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G et al (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381(9873):1203–1210PubMedCrossRefGoogle Scholar
  61. 61.
    Ghielmini M, Schmitz SF, Cogliatti S, Bertoni F, Waltzer U, Fey MF, Betticher DC, Schefer H et al (2005) Effect of single-agent rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research (SAKK). J Clin Oncol 23(4):705–711PubMedCrossRefGoogle Scholar
  62. 62.
    Schulz H, Bohlius JF, Trelle S, Skoetz N, Reiser M, Kober T, Schwarzer G, Herold M et al (2007) Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 99(9):706–714PubMedCrossRefGoogle Scholar
  63. 63.
    Forstpointner R, Dreyling M, Repp R, Hermann S, Hanel A, Metzner B, Pott C, Hartmann F et al (2004) The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104(10):3064–3071PubMedCrossRefGoogle Scholar
  64. 64.
    Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, Eimermacher H, Neubauer A et al (2005) Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 23(9):1984–1992PubMedCrossRefGoogle Scholar
  65. 65.
    Herold M, Pasold R, Srock S, Neser S, Niederwieser D, Neubauer A (2004) Results of a prospective randomised open label phase III study comparing rituximab plus mitoxantrone, chlorambucile, prednisolone chemotherapy (R-MCP) versus MCP alone in untreated advanced indolent non-Hodgkin’s lymphoma (NHL) and mantle-cell-lymphoma (MCL). Blood 104 (11 ASH annual meeting abstracts):169Google Scholar
  66. 66.
    Gianni AM, Magni M, Martelli M, Di Nicola M, Carlo-Stella C, Pilotti S, Rambaldi A, Cortelazzo S et al (2003) Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen). Blood 102(2):749–755PubMedCrossRefGoogle Scholar
  67. 67.
    Lefrère F, Delmer A, Suzan F, Levy V, Belanger C, Djabarri M, Arnulf B, Damaj G et al (2002) Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study. Leukemia 16(4):587–593PubMedCrossRefGoogle Scholar
  68. 68.
    van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL (2009) High-dose Ara-C and beam with autograft rescue in RCHOP responsive mantle cell lymphoma patients. Br J Haematol 144(4):524–530Google Scholar
  69. 69.
    Khouri IF, Saliba RM, Hosing C, Okoroji GJ, Acholonu S, Anderlini P, Couriel D, De Lima M et al (2005) Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin’s lymphomas. J Clin Oncol 23(10):2240–2247PubMedCrossRefGoogle Scholar
  70. 70.
    Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, McLaughlin P, Younes A et al (2005) High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 23(28):7013–7023PubMedCrossRefGoogle Scholar
  71. 71.
    Romaguera JE, Fayad LE, Feng L, Hartig K, Weaver P, Rodriguez MA, Hagemeister FB, Pro B et al (2010) Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 150(2):200–208PubMedGoogle Scholar
  72. 72.
    Epner EM, Unger J, Miller T, Rimzsa L, Spier C, Leblanc M, Fisher R (2007) A Multi center trial of hyperCVAD + Rituxan in patients with newly diagnosed mantle cell lymphoma. Blood 110 (11 ASH annual meeting abstracts):387Google Scholar
  73. 73.
    Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA et al (2009) Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol 27(36):6101–6108PubMedCrossRefGoogle Scholar
  74. 74.
    Geisler CH (2010) Front-line treatment of mantle cell lymphoma. Haematologica 95(8):1241–1243PubMedCrossRefGoogle Scholar
  75. 75.
    Pott C, Hoster E, Beldjord K, Macintyre EA, Bottcher S, Asnafi V, Siebert R, Plonquet A et al. (2010) R-CHOP/R-DHAP compared to R-CHOP induction followed by high dose therapy with autologous stem cell transplantation induces higher rates of molecular remission. In: MCL: results of the MCL Younger Intergroup Trial of the European MCL Network. Blood 116 (21 ASH Annual Meeting Abstracts):965Google Scholar
  76. 76.
    Hermine O, Hoster E, Walewski J, Ribrag V, Brousse N, Thieblemont C, Bouabdallah R, Dohner H et al. (2012) Alternating courses of 3× CHOP and 3× DHAP Plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net). Blood 120 (21 ASH Annual Meeting Abstracts):151Google Scholar
  77. 77.
    Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L et al (2005) Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 105(7):2677–2684PubMedCrossRefGoogle Scholar
  78. 78.
    Andersen NS, Pedersen L, Elonen E, Johnson A, Kolstad A, Franssila K, Langholm R, Ralfkiaer E et al (2003) Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant. Eur J Haematol 71(2):73–80PubMedCrossRefGoogle Scholar
  79. 79.
    Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordstrom M et al (2008) Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood 112(7):2687–2693PubMedCrossRefGoogle Scholar
  80. 80.
    Geisler CH. Update of the Nordic MCL2 trial update: 10-year survival 57% following intensive immunotherapy and ASCT, but late relapses do occur. In: 11th International Conference on Malignant Lymphoma, Lugano, Switzerland. June 15–18, 2011Google Scholar
  81. 81.
    Tam CS, Bassett R, Ledesma C, Korbling M, Alousi A, Hosing C, Kebraei P, Harrell R et al (2009) Mature results of the M.D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood 113(18):4144–4152PubMedCrossRefGoogle Scholar
  82. 82.
    Pott C, Hoster E, Delfau-Larue MH, Beldjord K, Bottcher S, Asnafi V, Plonquet A, Siebert R et al (2010) Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood 115(16):3215–3223PubMedCrossRefGoogle Scholar
  83. 83.
    Howard OM, Gribben JG, Neuberg DS, Grossbard M, Poor C, Janicek MJ, Shipp MA (2002) Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol 20(5):1288–1294PubMedCrossRefGoogle Scholar
  84. 84.
    Budde LE, Guthrie KA, Till BG, Press OW, Chauncey TR, Pagel JM, Petersdorf SH, Bensinger WI et al (2011) Mantle cell lymphoma international prognostic index but not pretransplantation induction regimen predicts survival for patients with mantle-cell lymphoma receiving high-dose therapy and autologous stem-cell transplantation. J Clin Oncol 29(22):3023–3029PubMedCrossRefGoogle Scholar
  85. 85.
    Talarico L, Chen G, Pazdur R (2004) Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 22(22):4626–4631PubMedCrossRefGoogle Scholar
  86. 86.
    Aapro M, Bernard-Marty C, Brain EG, Batist G, Erdkamp F, Krzemieniecki K, Leonard R, Lluch A et al (2011) Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. Ann Oncol 22(2):257–267PubMedCrossRefGoogle Scholar
  87. 87.
    Meusers P, Engelhard M, Bartels H, Binder T, Fulle HH, Gorg K, Gunzer U, Havemann K et al (1989) Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: anthracycline does not improve the prognosis. Hematol Oncol 7(5):365–380PubMedCrossRefGoogle Scholar
  88. 88.
    Smith MR (2003) Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 22(47):7359–7368PubMedCrossRefGoogle Scholar
  89. 89.
    Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C et al (2012) Treatment of older patients with mantle-cell lymphoma. N Engl J Med 367(6):520–531PubMedCrossRefGoogle Scholar
  90. 90.
    Jantunen E, Canals C, Attal M, Thomson K, Milpied N, Buzyn A, Ferrant A, Biron P et al (2012) Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 23(1):166–171PubMedCrossRefGoogle Scholar
  91. 91.
    Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF et al (2006) Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 108(13):4003–4008PubMedCrossRefGoogle Scholar
  92. 92.
    Kahl BS, Longo WL, Eickhoff JC, Zehnder J, Jones C, Blank J, McFarland T, Bottner W et al (2006) Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol 17(9):1418–1423PubMedCrossRefGoogle Scholar
  93. 93.
    Jurczak W, Giza A, Krochmalczyk D, Sobocinski M, Zimowska-Curylo D, Stella-Holowiecka B, Boguradzki P, Kisiel E et al (2009) Survival benefit of post induction consolidation therapy in MCL (mantle cell lymphoma): a Polish Lymphoma Research Group (PLRG) retrospective multicenter analysis. ASCO Meeting Abstracts 27(15S):e19510Google Scholar
  94. 94.
    Smith MR, Zhang L, Gordon LI, Foran J, Kahl B, Gascoyne RD, Advani R, Paietta E et al. (2007) Phase II study of R-CHOP followed by 90Y-ibritumomab tiuxetan in untreated mantle cell lymphoma: Eastern Cooperative Oncology Group Study E1499. Blood 110 (11 ASH Annual Meeting Abstracts):389Google Scholar
  95. 95.
    Arranz R, Garcia-Noblejas A, Grande C, Terol J, Sanchez JJ, Perez-Calvo J, Canales M, Garcia-Marco JA et al. (2009) Feasability and toxicity after induction treatment with rituximab-HCVAD and metotrexate/citarabine, followed by consolidation with Y-90 ibritumomab tiuxetan (phase II GELTAMO-LCM 04–02 study). Blood 114 (22 ASH Annual Meeting Abstracts):1703Google Scholar
  96. 96.
    Kolstad A, Laurell A, Andersen NS, Elonen E, Raty R, Pedersen LB, Loft A, Bogsrud TV et al. (2009) 90y-Ibritumumab Tiuxetan (Zevalin (R))-BEAM/C with autologous stem cell support as frontline therapy for advanced mantle cell lymphoma. Preliminary results from the Third Nordic MCL Phase II Study (MCL3). Blood 114 (22 ASH Annual Meeting Abstracts):932Google Scholar
  97. 97.
    Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J et al (2010) Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group. Haematologica 95(8):1350–1357PubMedCrossRefGoogle Scholar
  98. 98.
    Sachanas S, Pangalis GA, Vassilakopoulos TP, Korkolopoulou P, Kontopidou FN, Athanasoulia M, Yiakoumis X, Kalpadakis C et al (2011) Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Leuk Lymphoma 52(3):387–393PubMedCrossRefGoogle Scholar
  99. 99.
    Rummel MJ, Kaiser U, Balser C, Stauch MB, Brugger W, Welslau M, Niederle N, Losem C et al. (2010) Bendamustine plus rituximab versus fludarabine plus rituximab in patients with relapsed follicular, indolent and mantle cell lymphomas. Final results of the Randomized Phase III Study NHL 2–2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). Blood 116 (21 ASH Annual Meeting Abstracts):856Google Scholar
  100. 100.
    Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, Drach J (2011) Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma. Haematologica 96(7):1008–1014PubMedCrossRefGoogle Scholar
  101. 101.
    Wang M, Fayad L, Cabanillas F, Hagemeister F, McLaughlin P, Rodriguez MA, Kwak LW, Zhou Y et al (2008) Phase 2 trial of rituximab plus hyper-CVAD alternating with rituximab plus methotrexate-cytarabine for relapsed or refractory aggressive mantle cell lymphoma. Cancer 113(10):2734–2741PubMedCrossRefGoogle Scholar
  102. 102.
    Witzig TE, Geyer SM, Kurtin PJ, Colgan JP, Inwards DJ, Micallef IN, LaPlant BR, Michalak JC et al (2008) Salvage chemotherapy with rituximab DHAP for relapsed non-Hodgkin lymphoma: a phase II trial in the North Central Cancer Treatment Group. Leuk Lymphoma 49(6):1074–1080PubMedCrossRefGoogle Scholar
  103. 103.
    Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B et al (2008) Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma. J Clin Oncol 26(27):4473–4479PubMedCrossRefGoogle Scholar
  104. 104.
    Weide R, Hess G, Koppler H, Heymanns J, Thomalla J, Aldaoud A, Losem C, Schmitz S et al (2007) High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma 48(7):1299–1306PubMedCrossRefGoogle Scholar
  105. 105.
    Johnson SA (2001) Nucleoside analogues in the treatment of haematological malignancies. Expert Opin Pharmacother 2(6):929–943PubMedCrossRefGoogle Scholar
  106. 106.
    Peters GJ, Ruiz van Haperen VW, Bergman AM, Veerman G, Smitskamp-Wilms E, van Moorsel CJ, Kuiper CM, Braakhuis BJ (1996) Preclinical combination therapy with gemcitabine and mechanisms of resistance. Semin Oncol 23(5 Suppl 10):16–24PubMedGoogle Scholar
  107. 107.
    Morschhauser F, Depil S, Jourdan E, Wetterwald M, Bouabdallah R, Marit G, Solal-Céligny P, Sebban C et al (2007) Phase II study of gemcitabine-dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma. Ann Oncol 18(2):370–375PubMedCrossRefGoogle Scholar
  108. 108.
    Gironella M, Lopez MDA, Pau A, Anny J, Noelia P, Bosch F (2010) Rituximab plus gemcitabine and oxaliplatin as salvage therapy in patients with relapsed/refractory mantle-cell lymphoma. Blood 116 (21 ASH Annual Meeting Abstracts):2825Google Scholar
  109. 109.
    Rodríguez J, Gutierrez A, Palacios A, Navarrete M, Blancas I, Alarcon J, Caballero MD, De Mattos SF et al (2007) Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma. Leuk Lymphoma 48(11):2172–2178PubMedCrossRefGoogle Scholar
  110. 110.
    Garbo LE, Flynn PJ, MacRae MA, Rauch MA, Wang Y, Kolibaba KS (2009) Results of a phase II trial of gemcitabine, mitoxantrone, and rituximab in relapsed or refractory mantle cell lymphoma. Invest New Drugs 27(5):476–481PubMedCrossRefGoogle Scholar
  111. 111.
    Dietrich S, Tielesch B, Rieger M, Nickelsen M, Pott C, Witzens-Harig M, Kneba M, Schmitz N et al (2011) Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma. Cancer 117(9):1901–1910PubMedCrossRefGoogle Scholar
  112. 112.
    Freedman AS, Neuberg D, Gribben JG, Mauch P, Soiffer RJ, Fisher DC, Anderson KC, Andersen N et al (1998) High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. J Clin Oncol 16(1):13–18PubMedGoogle Scholar
  113. 113.
    Vandenberghe E, Ruiz de Elvira C, Loberiza FR, Conde E, Lopez-Guillermo A, Gisselbrecht C, Guilhot F, Vose JM et al (2003) Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries. Br J Haematol 120(5):793–800PubMedCrossRefGoogle Scholar
  114. 114.
    Milpied N, Gaillard F, Moreau P, Mahe B, Souchet J, Rapp MJ, Bulabois CE, Morineau N et al (1998) High-dose therapy with stem cell transplantation for mantle cell lymphoma: results and prognostic factors, a single center experience. Bone Marrow Transplant 22(7):645–650PubMedCrossRefGoogle Scholar
  115. 115.
    Vose JM, Bierman PJ, Weisenburger DD, Lynch JC, Bociek Y, Chan WC, Greiner TC, Armitage JO (2000) Autologous hematopoietic stem cell transplantation for mantle cell lymphoma. Biol Blood Marrow Transplant 6(6):640–645PubMedCrossRefGoogle Scholar
  116. 116.
    Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP (2010) Management of mantle cell lymphoma: key challenges and next steps. Clin Lymphoma Myeloma Leuk 10(5):336–346PubMedCrossRefGoogle Scholar
  117. 117.
    Krishnan A, Nademanee A, Fung HC, Raubitschek AA, Molina A, Yamauchi D, Rodriguez R, Spielberger RT et al (2008) Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and high-dose chemotherapy in patients with non-Hodgkin’s lymphoma. J Clin Oncol 26(1):90–95PubMedCrossRefGoogle Scholar
  118. 118.
    Gopal AK, Rajendran JG, Petersdorf SH, Maloney DG, Eary JF, Wood BL, Gooley TA, Bush SA et al (2002) High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood 99(9):3158–3162PubMedCrossRefGoogle Scholar
  119. 119.
    Khouri IF, Lee MS, Saliba RM, Jun G, Fayad L, Younes A, Pro B, Acholonu S et al (2003) Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 21(23):4407–4412PubMedCrossRefGoogle Scholar
  120. 120.
    Cook G, Smith GM, Kirkland K, Lee J, Pearce R, Thomson K, Morris E, Orchard K et al (2010) Outcome following reduced-intensity allogeneic stem cell transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 16(10):1419–1427PubMedCrossRefGoogle Scholar
  121. 121.
    Corradini P, Dodero A, Farina L, Fanin R, Patriarca F, Miceli R, Matteucci P, Bregni M et al (2007) Allogeneic stem cell transplantation following reduced-intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome. Leukemia 21(11):2316–2323PubMedCrossRefGoogle Scholar
  122. 122.
    Maris MB, Sandmaier BM, Storer BE, Chauncey T, Stuart MJ, Maziarz RT, Agura E, Langston AA et al (2004) Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 104(12):3535–3542PubMedCrossRefGoogle Scholar
  123. 123.
    Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR, Taghipour G, Schmitz N (2002) Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 100(13):4310–4316PubMedCrossRefGoogle Scholar
  124. 124.
    Kahl C, Storer BE, Sandmaier BM, Mielcarek M, Maris MB, Blume KG, Niederwieser D, Chauncey TR et al (2007) Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 110(7):2744–2748PubMedCrossRefGoogle Scholar
  125. 125.
    Hartmann M, Zimmer C (1972) Investigation of cross-link formation in DNA by the alkylating cytostatic IMET 3106, 3393 and 3943. Biochim Biophys Acta 287(3):386–389PubMedCrossRefGoogle Scholar
  126. 126.
    Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G, Niemeyer CC (2008) Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res 14(1):309–317PubMedCrossRefGoogle Scholar
  127. 127.
    Ogura M, Uchida T, Ando K, Ohmachi K, Itoh K, Kubota N, Ishizawa K, Yamamoto J et al. (2009) Bendamustine Is highly effective for relapsed or refractory indolent b-cell non-hodgkin lymphoma (B-NHL) and mantle cell lymphoma (MCL): final results of a Japanese Multicenter Phase II Study. Blood 114 (22 ASH Annual Meeting Abstracts):3694Google Scholar
  128. 128.
    Bauwens D, Maerevoet M, Michaux L, Theate I, Hagemeijer A, Stul M, Danse E, Costantini S et al (2005) Activity and safety of combined rituximab with chlorambucil in patients with mantle cell lymphoma. Br J Haematol 131(3):338–340PubMedCrossRefGoogle Scholar
  129. 129.
    Hiddemann W, Unterhalt M, Herrmann R, Woltjen HH, Kreuser ED, Trumper L, Reuss-Borst M, Terhardt-Kasten E et al (1998) Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol 16(5):1922–1930PubMedGoogle Scholar
  130. 130.
    Leonard JP, Schattner EJ, Coleman M (2001) Biology and management of mantle cell lymphoma. Curr Opin Oncol 13(5):342–347PubMedCrossRefGoogle Scholar
  131. 131.
    Williams ME, Densmore JJ (2005) Biology and therapy of mantle cell lymphoma. Curr Opin Oncol 17(5):425–431PubMedCrossRefGoogle Scholar
  132. 132.
    Ansell SM, Inwards DJ, Rowland KM Jr, Flynn PJ, Morton RF, Moore DF Jr, Kaufmann SH, Ghobrial I et al (2008) Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer 113(3):508–514PubMedCrossRefGoogle Scholar
  133. 133.
    Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, Ansell SM, Luyun R et al (2005) Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23(23):5347–5356PubMedCrossRefGoogle Scholar
  134. 134.
    Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F et al (2009) Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 27(23):3822–3829PubMedCrossRefGoogle Scholar
  135. 135.
    Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A et al (2006) Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 24(30):4867–4874PubMedCrossRefGoogle Scholar
  136. 136.
    Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A et al (2009) Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 20(3):520–525PubMedCrossRefGoogle Scholar
  137. 137.
    Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL et al (2011) Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. The Lancet Oncology 12(4):361–368PubMedCrossRefGoogle Scholar
  138. 138.
    Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J et al (2011) Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 29(6):690–697PubMedCrossRefGoogle Scholar
  139. 139.
    Romaguera JE, Fayad LE, McLaughlin P, Pro B, Rodriguez A, Wang M, Weaver P, Hartig K et al (2010) Phase I trial of bortezomib in combination with rituximab-HyperCVAD alternating with rituximab, methotrexate and cytarabine for untreated aggressive mantle cell lymphoma. Br J Haematol 151(1):47–53PubMedCrossRefGoogle Scholar
  140. 140.
    Wang M, Rule SA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH et al. (2012) Interim results of an international, multicenter, phase 2 study of Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), in relapsed or refractory mantle cell lymphoma (MCL): durable efficacy and tolerability with longer follow-up. Blood 120 (21 ASH Annual Meeting Abstracts):904Google Scholar
  141. 141.
    Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM et al (2011) A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia 25(2):341–347PubMedCrossRefGoogle Scholar
  142. 142.
    Bjornsti MA, Houghton PJ (2004) The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4(5):335–348PubMedCrossRefGoogle Scholar
  143. 143.
    Temsirolimus: CCI 779, CCI-779, cell cycle inhibitor-779 (2004). Drugs R D 5(6):363–367Google Scholar
  144. 144.
    Del Bufalo D, Ciuffreda L, Trisciuoglio D, Desideri M, Cognetti F, Zupi G, Milella M (2006) Antiangiogenic potential of the mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 66(11):5549–5554PubMedCrossRefGoogle Scholar
  145. 145.
    Hess G, Kang L, Moran PJ (2011) Effect of prognostic risk classification on temsirolimus efficacy and safety outcomes in patients with relapsed/refractory mantle cell lymphoma. Blood 2011 (21 ASH annual meeting abstracts):2708Google Scholar
  146. 146.
    Hess G, Keller U, Atta J, Buske C, Borchmann P, Medler C, Witzens-Harig M, Dreyling MH (2011) Temsirolimus in combination with bendamustine and rituximab for the treatment of relapsed mantle cell and follicular lymphoma: report on an ongoing phase I/II trial. Blood 118 (21 ASH Annual meeting abstracts):623Google Scholar
  147. 147.
    Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, Schafer PH, Chen R et al (2007) Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res 67(2):746–755PubMedCrossRefGoogle Scholar
  148. 148.
    Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B et al (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96(9):2943–2950PubMedGoogle Scholar
  149. 149.
    Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW, Chen RS, Muller GW et al (2009) The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res 77(2):78–86PubMedCrossRefGoogle Scholar
  150. 150.
    Chang DH, Liu N, Klimek V, Hassoun H, Mazumder A, Nimer SD, Jagannath S, Dhodapkar MV (2006) Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 108(2):618–621PubMedCrossRefGoogle Scholar
  151. 151.
    Ramsay AG, Johnson AJ, Lee AM, Gorgun G, Le Dieu R, Blum W, Byrd JC, Gribben JG (2008) Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest 118(7):2427–2437PubMedGoogle Scholar
  152. 152.
    Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357(21):2123–2132PubMedCrossRefGoogle Scholar
  153. 153.
    Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K et al (2008) Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol 26(30):4952–4957PubMedCrossRefGoogle Scholar
  154. 154.
    Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-Haynes A et al (2009) Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 145(3):344–349PubMedCrossRefGoogle Scholar
  155. 155.
    Zaja F, De Luca S, Vitolo U, Orsucci L, Levis A, Salvi F, Rusconi C, Ravelli E et al (2012) Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers. Haematologica 97(3):416–422PubMedCrossRefGoogle Scholar
  156. 156.
    Pham LV, Tamayo AT, Yoshimura LC, Lo P, Ford RJ (2003) Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol 171(1):88–95PubMedGoogle Scholar
  157. 157.
    Chiarle R, Budel LM, Skolnik J, Frizzera G, Chilosi M, Corato A, Pizzolo G, Magidson J et al (2000) Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma. Blood 95(2):619–626PubMedGoogle Scholar
  158. 158.
    Perez-Galan P, Roue G, Villamor N, Montserrat E, Campo E, Colomer D (2006) The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood 107(1):257–264PubMedCrossRefGoogle Scholar
  159. 159.
    Kahl BS, Li H, Smith MR, Gascoyne RD, Yang DT, Paietta E, Advani RH, Horning SJ (2012) Mature results from ECOG study E1405—a phase II study of VcR-CVAD with maintenance rituximab for previously untreated mantle cell lymphoma. Blood 120 (21 ASH Annual Meeting Abstracts):153Google Scholar
  160. 160.
    Dreger P, Laport GG (2008) Controversies in lymphoma: the role of hematopoietic cell transplantation for mantle cell lymphoma and peripheral T cell lymphoma. Biol Blood Marrow Transplant 14(1 Suppl 1):100–107PubMedCrossRefGoogle Scholar
  161. 161.
    Brizova H, Kalinova M, Krskova L, Mrhalova M, Kodet R (2008) Quantitative monitoring of cyclin D1 expression: a molecular marker for minimal residual disease monitoring and a predictor of the disease outcome in patients with mantle cell lymphoma. Int J Cancer 123(12):2865–2870PubMedCrossRefGoogle Scholar
  162. 162.
    Böttcher S, Ritgen M, Buske S, Gesk S, Klapper W, Hoster E, Hiddemann W, Unterhalt M et al (2008) Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations. Haematologica 93(4):551–559PubMedCrossRefGoogle Scholar
  163. 163.
    Corradini P, Ladetto M, Pileri A, Tarella C (1999) Clinical relevance of minimal residual disease monitoring in non-Hodgkin’s lymphomas: a critical reappraisal of molecular strategies. Leukemia 13(11):1691–1695PubMedCrossRefGoogle Scholar
  164. 164.
    van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17(12):2257–2317PubMedCrossRefGoogle Scholar
  165. 165.
    van der Velden VH, Cazzaniga G, Schrauder A, Hancock J, Bader P, Panzer-Grumayer ER, Flohr T, Sutton R et al (2007) Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 21(4):604–611PubMedGoogle Scholar
  166. 166.
    van Krieken JH, Langerak AW, Macintyre EA, Kneba M, Hodges E, Sanz RG, Morgan GJ, Parreira A et al (2007) Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21(2):201–206PubMedCrossRefGoogle Scholar
  167. 167.
    Hamborg KH, Bentzen HH, Grubach L, Hokland P, Nyvold CG (2012) A highly sensitive and specific qPCR assay for quantification of the biomarker SOX11 in mantle cell lymphoma. Eur J Haematol 89(5):385–394PubMedCrossRefGoogle Scholar
  168. 168.
    Itala M, Huhtinen AR, Juvonen V, Kairisto V, Pelliniemi TT, Penttila TL, Rauhala A, Tienhaara A et al (2008) Stem cell transplantation in poor-risk chronic lymphocytic leukemia: assessment of post-transplant minimal residual disease using four- and six-color flow cytometry and allele-specific RQ-PCR. Eur J Haematol 81(2):100–106PubMedCrossRefGoogle Scholar
  169. 169.
    Verhagen OJ, Willemse MJ, Breunis WB, Wijkhuijs AJ, Jacobs DC, Joosten SA, van Wering ER, van Dongen JJ et al (2000) Application of germline IGH probes in real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia. Leukemia 14(8):1426–1435PubMedCrossRefGoogle Scholar
  170. 170.
    Garcia-Castillo H, Barros-Nunez P (2009) Detection of clonal immunoglobulin and T-cell receptor gene recombination in hematological malignancies: monitoring minimal residual disease. Cardiovasc Hematol Disord Drug Targets 9(2):124–135PubMedCrossRefGoogle Scholar
  171. 171.
    Pittaluga S, Tierens A, Pinyol M, Campo E, Delabie J, De Wolf-Peeters C (1998) Blastic variant of mantle cell lymphoma shows a heterogenous pattern of somatic mutations of the rearranged immunoglobulin heavy chain variable genes. Br J Haematol 102(5):1301–1306PubMedCrossRefGoogle Scholar
  172. 172.
    Hummel M, Tamaru J, Kalvelage B, Stein H (1994) Mantle cell (previously centrocytic) lymphomas express VH genes with no or very little somatic mutations like the physiologic cells of the follicle mantle. Blood 84(2):403–407PubMedGoogle Scholar
  173. 173.
    Gonzalez D, Garcia-Sanz R (2005) Incomplete DJH rearrangements. Methods Mol Med 113:165–173PubMedGoogle Scholar
  174. 174.
    Andersen NS, Donovan JW, Borus JS, Poor CM, Neuberg D, Aster JC, Nadler LM, Freedman AS et al (1997) Failure of immunologic purging in mantle cell lymphoma assessed by polymerase chain reaction detection of minimal residual disease. Blood 90(10):4212–4221PubMedGoogle Scholar
  175. 175.
    Corradini P, Ladetto M, Zallio F, Astolfi M, Rizzo E, Sametti S, Cuttica A, Rosato R et al (2004) Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes. J Clin Oncol 22(8):1460–1468PubMedCrossRefGoogle Scholar
  176. 176.
    Brugger W, Hirsch J, Grunebach F, Repp R, Brossart P, Vogel W, Kopp HG, Manz MG et al (2004) Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study. Ann Oncol 15(11):1691–1698PubMedCrossRefGoogle Scholar
  177. 177.
    Ladetto M, Magni M, Pagliano G, De Marco F, Drandi D, Ricca I, Astolfi M, Matteucci P et al (2006) Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma. Biol Blood Marrow Transplant 12(12):1270–1276PubMedCrossRefGoogle Scholar
  178. 178.
    Liu H, Johnson JL, Koval G, Malnassy G, Sher D, Damon LE, Hsi ED, Bucci DM et al (2012) Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909. Haematologica 97(4):579–585PubMedCrossRefGoogle Scholar
  179. 179.
    Andersen NS, Pedersen LB, Laurell A, Elonen E, Kolstad A, Boesen AM, Pedersen LM, Lauritzsen GF et al (2009) Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma. J Clin Oncol 27(26):4365–4370PubMedCrossRefGoogle Scholar
  180. 180.
    van der Velden VH, Hochhaus A, Cazzaniga G, Szczepanski T, Gabert J, van Dongen JJ (2003) Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia 17(6):1013–1034PubMedCrossRefGoogle Scholar
  181. 181.
    Sutton R, Bahar AY, Kwan E, Giles JE, Venn NC, Tran S, Hackenberg N, Pozza LD et al (2008) Improving minimal residual disease detection in precursor B-ALL based on immunoglobulin-kappa and heavy-chain gene rearrangements. Leukemia 22(12):2265–2267PubMedCrossRefGoogle Scholar
  182. 182.
    Sanchez ML, Almeida J, Vidriales B, Lopez-Berges MC, Garcia-Marcos MA, Moro MJ, Corrales A, Calmuntia MJ et al (2002) Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: basis for the design of specific four-color stainings to be used for minimal residual disease investigation. Leukemia 16(8):1460–1469PubMedCrossRefGoogle Scholar
  183. 183.
    Pedreira CE, Costa ES, Almeida J, Fernandez C, Quijano S, Flores J, Barrena S, Lecrevisse Q et al (2008) A probabilistic approach for the evaluation of minimal residual disease by multiparameter flow cytometry in leukemic B-cell chronic lymphoproliferative disorders. Cytometry A 73A(12):1141–1150PubMedCrossRefGoogle Scholar
  184. 184.
    Szczepanski T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ (2001) Minimal residual disease in leukaemia patients. Lancet Oncol 2(7):409–417PubMedCrossRefGoogle Scholar
  185. 185.
    van Dongen JJ, Orfao A (2012) EuroFlow: resetting leukemia and lymphoma immunophenotyping. Basis for companion diagnostics and personalized medicine Leukemia 26(9):1899–1907Google Scholar
  186. 186.
    van Dongen JJ, Lhermitte L, Bottcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, Asnafi V et al (2012) EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia 26(9):1908–1975PubMedCrossRefGoogle Scholar
  187. 187.
    Teodorovic I, Pittaluga S, Kluin-Nelemans JC, Meerwaldt JH, Hagenbeek A, van Glabbeke M, Somers R, Bijnens L et al (1995) Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin’s lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group J Clin Oncol 13(11):2819–2826Google Scholar
  188. 188.
    Unterhalt M, Herrmann R, Tiemann M, Parwaresch R, Stein H, Trumper L, Nahler M, Reuss-Borst M et al (1996) Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin’s lymphoma. German Low-Grade Lymphoma Study Group Leukemia 10(5):836–843Google Scholar
  189. 189.
    Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E et al (2006) Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer 107(5):1014–1022PubMedCrossRefGoogle Scholar
  190. 190.
    Herold M, Dolken G, Fiedler F, Franke A, Freund M, Helbig W, Pasold R (2003) Randomized phase III study for the treatment of advanced indolent non-Hodgkin’s lymphomas (NHL) and mantle cell lymphoma: chemotherapy versus chemotherapy plus rituximab. Ann Hematol 82(2):77–79PubMedGoogle Scholar
  191. 191.
    Khouri IF, Romaguera J, Kantarjian H, Palmer JL, Pugh WC, Korbling M, Hagemeister F, Samuels B et al (1998) Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol 16(12):3803–3809PubMedGoogle Scholar
  192. 192.
    Romaguera JE, Khouri IF, Kantarjian HM, Hagemeister FB, Rodriguez MA, McLaughlin P, Sarris AH, Younes A et al (2000) Untreated aggressive mantle cell lymphoma: results with intensive chemotherapy without stem cell transplant in elderly patients. Leuk Lymphoma 39(1–2):77–85PubMedCrossRefGoogle Scholar
  193. 193.
    Merli F, Luminari S, Ilariucci F, Stelitano C, Petrini M, Di Renzo N, Angrilli F, Carella AM et al. (2008) Rituximab plus hypercvad alternating with high dose methotrexate and cytarabine for patients with newly diagnosed mantle cell lymphoma. A Multicenter Trial from GISL. Blood 112 (11 ASH Annual Meeting Abstracts):3050Google Scholar
  194. 194.
    de Guibert S, Jaccard A, Bernard M, Turlure P, Bordessoule D, Lamy T (2006) Rituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma. Haematologica 91(3):425–426PubMedGoogle Scholar
  195. 195.
    Lefrère F, Delmer A, Levy V, Delarue R, Varet B, Hermine O (2004) Sequential chemotherapy regimens followed by high-dose therapy with stem cell transplantation in mantle cell lymphoma: an update of a prospective study. Haematologica 89(10):1275–1276PubMedGoogle Scholar
  196. 196.
    Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A et al (2013) CHOP and DHAP plus rituximab followed by autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL): a phase II study from the GELA. Blood 121(1):48–53PubMedCrossRefGoogle Scholar
  197. 197.
    Dreger P, Rieger M, Seyfarth B, Hensel M, Kneba M, Ho AD, Schmitz N, Pott C (2007) Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome. Haematologica 92(1):42–49PubMedCrossRefGoogle Scholar
  198. 198.
    Khouri IF, Saliba RM, Okoroji GJ, Acholonu SA, Champlin RE (2003) Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer 98(12):2630–2635PubMedCrossRefGoogle Scholar
  199. 199.
    Mangel J, Leitch HA, Connors JM, Buckstein R, Imrie K, Spaner D, Crump M, Pennell N et al (2004) Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis. Ann Oncol 15(2):283–290PubMedCrossRefGoogle Scholar
  200. 200.
    Magni M, Di Nicola M, Carlo-Stella C, Matteucci P, Devizzi L, Tarella C, Benedetti F, Martelli M et al (2009) High-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting in mantle cell lymphoma: a 10-year update of the R-HDS regimen. Bone Marrow Transplant 43(6):509–511PubMedCrossRefGoogle Scholar
  201. 201.
    Cohen BJ, Moskowitz C, Straus D, Noy A, Hedrick E, Zelenetz A (2001) Cyclophosphamide/fludarabine (CF) is active in the treatment of mantle cell lymphoma. Leuk Lymphoma 42(5):1015–1022PubMedCrossRefGoogle Scholar
  202. 202.
    Herold M, Schulze A, Niederwieser D, Franke A, Fricke HJ, Richter P, Freund M, Ismer B et al (2006) Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19). J Cancer Res Clin Oncol 132(2):105–112PubMedCrossRefGoogle Scholar
  203. 203.
    Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Durk H et al (2005) Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. J Clin Oncol 23(15):3383–3389PubMedCrossRefGoogle Scholar
  204. 204.
    Josting A, Reiser M, Wickramanayake PD, Rueffer U, Draube A, Sohngen D, Tesch H, Wolf J et al (2000) Dexa-BEAM: an effective regimen for cytoreduction prior to high-dose chemotherapy with autologous stem cell support for patients with relapsed/refractory mantle-cell lymphoma. Leuk Lymphoma 37(1–2):185–187PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Dolores Caballero
    • 1
  • Elías Campo
    • 2
  • Armando López-Guillermo
    • 3
  • Alejandro Martín
    • 1
  • Reyes Arranz-Sáez
    • 4
  • Eva Giné
    • 3
  • Andrés López
    • 5
  • Eva González-Barca
    • 6
  • Miguel Ángel Canales
    • 7
  • Marcos González-Díaz
    • 8
  • Alberto Orfao
    • 9
  1. 1.Department of Hematology, Hospital Clínico UniversitarioInstituto de Investigación Biomédica de Salamanca (IBSAL)SalamancaSpain
  2. 2.Department of Pathology, Hospital ClínicUniversity of BarcelonaBarcelonaSpain
  3. 3.Department of Hematology, Hospital ClínicUniversity of BarcelonaBarcelonaSpain
  4. 4.Department of HematologyHospital Universitario La PrincesaMadridSpain
  5. 5.Department of HematologyHospital Vall d’HebronBarcelonaSpain
  6. 6.Institut Catalá d’OncologiaBarcelonaSpain
  7. 7.Hospital Universitario La PazMadridSpain
  8. 8.Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Molecular Biology/Histocompatibility Unit, Department of HematologyIBSAL-University HospitalSalamancaSpain
  9. 9.Department of Medicine, Cytometry Service, Cancer Research Centre (IBMCC-USAL/CSIC)University of SalamancaSalamancaSpain

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