Treatment of adult T-cell leukaemia/lymphoma: current strategy and future perspectives

被引:56
作者
Bazarbachi, A
Hermine, O
机构
[1] Amer Univ Beirut, Dept Internal Med, Beirut 6044, Lebanon
[2] Hop Necker Enfants Malad, Dept Hematol, Paris, France
关键词
conventional chemotherapy; leukaemia; lymphoma;
D O I
10.1016/S0168-1702(01)00286-6
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human T-cell leukaemia virus type I (HTLV-1) associated adult T-cell leukaemia/lymphoma (ATL) carries a very poor prognosis due to an intrinsic resistance of leukaemic cells to conventional or even high doses of chemotherapy and to an associated severe immunosuppression. Therefore, the potential role of conventional chemotherapy, high dose chemotherapy with autologous or allogeneic bone marrow transplantation remains to be defined. Important progress was achieved in the treatment of ATL with the combination of zidovudine (AZT) and interferon-alpha (IFN) which produces a high response rate in ATL patients with minimal side effects. This treatment seems to prolong the survival of patients much more than intensive chemotherapy. The success of this potentially anti-retroviral approach in the treatment of ATL suggests the existence of continuous HTLV-I replication in vivo. These encouraging results may be improved by the use of higher doses of AZT and IFN combined with other anti-retroviral agents. However, since cure seems still elusive, new therapeutic approaches or new combinations are required. For example, biological mediators such as retinoid acid, which induces apoptosis of ATL cells in vitro, may reduce drug resistance and stimulates immunity to restore anti-tumour activity against ATL cells. Alternatively, immunotherapy with anti-interleukin-2 receptor monoclonal antibodies or injection of cytotoxic T-cells directed against virus antigens could be interesting approaches which may merit further investigations in the near future. Finally, the recent demonstration that the combination of arsenic trioxide (As) and IFN induces a specific degradation of the viral transactivator Tax followed by cell cycle arrest and apoptosis of HTLV-I positive cells may constitute a valuable addition to ATL treatment. (C) 2001 Elsevier Science BN. All rights reserved.
引用
收藏
页码:79 / 92
页数:14
相关论文
共 84 条
  • [11] DEOXYCOFORMYCIN IN THE TREATMENT OF MATURE T-CELL LEUKEMIAS
    DEARDEN, C
    MATUTES, E
    CATOVSKY, D
    [J]. BRITISH JOURNAL OF CANCER, 1991, 64 (05) : 903 - 906
  • [12] El-Sabban ME, 2000, BLOOD, V96, P2849
  • [13] EZAKI K, 1991, CANCER, V68, P695, DOI 10.1002/1097-0142(19910815)68:4<695::AID-CNCR2820680405>3.0.CO
  • [14] 2-K
  • [15] Retinoic acids induce growth inhibition and apoptosis in adult T-cell leukemia (ATL) cell lines
    Fujimura, S
    Suzumiya, J
    Anzai, K
    Ohkubo, K
    Hata, T
    Yamada, Y
    Kamihira, S
    Kikuchi, M
    Ono, J
    [J]. LEUKEMIA RESEARCH, 1998, 22 (07) : 611 - 618
  • [16] Induction of the WAF1/CIP1 protein and apoptosis in human T-cell leukemia virus type I-transformed lymphocytes after treatment with Adriamycin by using a p53-independent pathway
    Gartenhaus, RB
    Wang, P
    Hoffmann, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) : 265 - 268
  • [17] GESSAIN A, 1985, LANCET, V2, P407
  • [18] GESSAIN A, 1996, HUMAN T CELL LYMPHOT, V1, P33
  • [19] TREATMENT OF ADULT T-CELL LEUKEMIA-LYMPHOMA WITH A COMBINATION OF INTERFERON-ALFA AND ZIDOVUDINE
    GILL, PS
    HARRINGTON, W
    KAPLAN, MH
    RIBEIRO, RC
    BENNETT, JM
    LIEBMAN, HA
    BERNSTEINSINGER, M
    ESPINA, BM
    CABRAL, L
    ALLEN, S
    KORNBLAU, S
    PIKE, MC
    LEVINE, AM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (26) : 1744 - 1748
  • [20] GOODMAN DS, 1984, NEW ENGL J MED, V310, P1023, DOI 10.1056/NEJM198404193101605