Chemotherapy of Aggressive Adult T-cell Leukemia/Lymphoma (ATL)

Chapter

Abstract

Treatment option for adult T-cell leukemia-lymphoma (ATL) is diverse, ranging from watchful waiting to intensive chemotherapy followed by allo-HSCT. A treatment strategy based on the clinical subtypes, prognostic factors, and response to initial therapy is suggested in an international consensus report (Tsukasaki et al. J Clin Oncol 27:453–459, 2009). Patients with acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL) generally have a very poor prognosis due to multidrug resistance of ATL cells, a large tumor burden with multi-organ failure, hypercalcemia, and/or opportunistic infections. In the case of aggressive ATL, intensive chemotherapy such as VCAP-AMP-VECP (mLSG15) is usually recommended based on the results of a phase III trial (JCOG 9801) (Tsukasaki et al. J Clin Oncol 25:5458–5464, 2007). Other strategies include watchful waiting until disease progression for favorable chronic or smoldering ATL (indolent ATL), up-front allo-HSCT for relatively young patients with aggressive ATL, the combination of interferon alpha and zidovudine (IFN/AZT) for types with leukemic manifestation, and defucosylated humanized anti-CCR4 monoclonal antibody (mogamulizmab) for relapsed/refractory CCR4-positive aggressive ATL (Ishida et al. J Clin Oncol 30:837–842, 2012). In this chapter, chemotherapy of aggressive ATL will be reviewed with reference to consecutive trials by JCOG-LSG followed by addition of mogamulizmab in Japan (Tsukasaki et al. Jpn J Clin Oncol 42:85–95, 2012).

Keywords

ATL Chemotherapy Clinical trials Lymphoma Study Group Japan Clinical Oncology Group Anti-CCR4 antibody 

References

  1. 1.
    Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington Jr W, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009;27:453–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007;25:5458–64.CrossRefPubMedGoogle Scholar
  3. 3.
    Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30:837–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Tsukasaki K, Tobinai K, Hotta T, Shimoyama M. Lymphoma Study Group of JCOG. Jpn J Clin Oncol. 2012;42:85–95.CrossRefPubMedGoogle Scholar
  5. 5.
    Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–30.CrossRefPubMedGoogle Scholar
  6. 6.
    Shimoyama M, Ichimaru M, Yunoki K, Oota K, Ogawa M. Final results of cooperative study of VEPA [vincristine, cyclophosphamide (endoxan), prednisolone and adriamycin] therapy in advanced adult non-Hodgkin’s lymphoma: relation between T- or B-Cell phenotype and response. Jpn J Clin Oncol. 1982;12:227–37.Google Scholar
  7. 7.
    Shimoyama M, Ota K, Kikuchi M, Yunoki K, Konda S, Takatsuki K, et al. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin’s lymphoma treated with VEPA or VEPA-M. J Clin Oncol. 1988;6:128–41.CrossRefPubMedGoogle Scholar
  8. 8.
    Tobinai K, Shimoyama M, Minato K, Shirakawa S, Kobayashi T, Hotta T, et al. Japan Clinical Oncology Group phase II trial of second-generation ‘LSG4 protocol’ in aggressive T- and B-lymphoma: a new predictive model for T-and B-lymphoma. Proc Am Soc Clin Oncol. 1994;13:378a. (Abstract)Google Scholar
  9. 9.
    Tobinai K, Uike N, Saburi Y, et al. Phase II study of cladribine (2-chlorodeoxyadenosine) in relapsed or refractory adult T-cell leukemia-lymphoma. Int J Hematol. 2003;77:512–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Tsukasaki K, Tobinai K, Shimoyama M, Kozuru M, Uike N, Yamada Y, et al. Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group study (JCOG9109). Int J Hematol. 2003;77:164–70.CrossRefPubMedGoogle Scholar
  11. 11.
    Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M, et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukemia-lymphoma (ATL): Japan Clinical Oncology Group (JCOG) Study 9303. Br J Haematol. 2001;113:375–82.CrossRefPubMedGoogle Scholar
  12. 12.
    Ohno N, Tani A, Uozumi K, et al. Expression of functional lung resistance–related protein predicts poor outcome in adult T-cell leukemia. Blood. 2001;98:1160–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Tsukasaki K, Ikeda S, Murata K, et al. Characteristics of chemotherapy-induced clinical remissionin long survivors with aggressive adult T-cell leukemia/lymphoma. Leuk Res. 1993;17:157–66.CrossRefPubMedGoogle Scholar
  14. 14.
    Ishida T, Utsunomiya A, Iida S, Inagaki H, Takatsuka Y, Kusumoto S, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res. 2003;9:3625–34.PubMedGoogle Scholar
  15. 15.
    Nakayama T, Hieshima K, Arao T, et al. Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia. Oncogene. 2008;27:3221–32.CrossRefPubMedGoogle Scholar
  16. 16.
    Nakagawa M, Schmitz R, Xiao W, et al. Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma. J Exp Med. 2014;211(13):2497–505.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010;28:1591–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Ishida T, Jo T, Takemoto S, et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015;169(5):672–82.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bazarbachi A, Plumelle Y, Ramos JC, Tortevoye P, Otrock Z, Taylor G, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol. 2010;27:417–23.Google Scholar
  20. 20.
    Hodson A, Crichton S, Montoto S, et al. Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma. J Clin Oncol. 2011;29(35):4696–701.CrossRefPubMedGoogle Scholar
  21. 21.
    Inoue Y, Fuji S, Tanosaki R, Fukuda T. Pretransplant mogamulizumab against ATLL might increase the risk of acute GVHD and non-relapse mortality. Bone Marrow Transplant. 2016 May;51(5):725–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Department of HematologyNational Cancer Center Hospital EastKashiwaJapan

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