Rita Hleihel1,2, Abdou Akkouche1,2, Hala Skayneh1,2, Olivier Hermine3, Ali Bazarbachi4,5, Hiba El Hajj6. 1. Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. 2. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. 3. Institut Imagine-INSERM U1163, Necker Hospital, University of Paris, 75015, Paris, France. 4. Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. bazarbac@aub.edu.lb. 5. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. bazarbac@aub.edu.lb. 6. Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. he21@aub.edu.lb.
Abstract
PURPOSE OF THE REVIEW: Adult T-cell leukemia (ATL) is an aggressive chemo-resistant malignancy secondary to HTLV-1 retrovirus. Prognosis of ATL remains dismal. Herein, we emphasized on the current ATL treatment modalities and their drawbacks, and opened up on promising targeted therapies with special focus on the HTLV-1 regulatory proteins Tax and HBZ. RECENT FINDINGS: Indolent ATL and a fraction of acute ATL exhibit long-term survival following antiviral treatment with zidovudine and interferon-alpha. Monoclonal antibodies such as mogamulizumab improved response rates, but with little effect on survival. Allogeneic hematopoietic cell transplantation results in long-term survival in one third of transplanted patients, alas only few patients are transplanted. Salvage therapy with lenalidomide in relapsed/refractory patients leads to prolonged survival in some of them. ATL remains an unmet medical need. Targeted therapies focusing on the HTLV-1 viral replication and/or viral regulatory proteins, as well as on the host antiviral immunity, represent a promising approach for the treatment of ATL.
PURPOSE OF THE REVIEW: Adult T-cell leukemia (ATL) is an aggressive chemo-resistant malignancy secondary to HTLV-1 retrovirus. Prognosis of ATL remains dismal. Herein, we emphasized on the current ATL treatment modalities and their drawbacks, and opened up on promising targeted therapies with special focus on the HTLV-1 regulatory proteins Tax and HBZ. RECENT FINDINGS: Indolent ATL and a fraction of acute ATL exhibit long-term survival following antiviral treatment with zidovudine and interferon-alpha. Monoclonal antibodies such as mogamulizumab improved response rates, but with little effect on survival. Allogeneic hematopoietic cell transplantation results in long-term survival in one third of transplanted patients, alas only few patients are transplanted. Salvage therapy with lenalidomide in relapsed/refractory patients leads to prolonged survival in some of them. ATL remains an unmet medical need. Targeted therapies focusing on the HTLV-1 viral replication and/or viral regulatory proteins, as well as on the host antiviral immunity, represent a promising approach for the treatment of ATL.
Authors: A Bazarbachi; M E El-Sabban; R Nasr; F Quignon; C Awaraji; J Kersual; L Dianoux; Y Zermati; J H Haidar; O Hermine; H de Thé Journal: Blood Date: 1999-01-01 Impact factor: 22.113
Authors: Philippe V Afonso; Mourad Mekaouche; Franck Mortreux; Frédéric Toulza; Antoine Moriceau; Eric Wattel; Antoine Gessain; Charles R M Bangham; Guy Dubreuil; Yves Plumelle; Olivier Hermine; Jérome Estaquier; Renaud Mahieux Journal: Blood Date: 2010-06-29 Impact factor: 22.113
Authors: A Bazarbachi; R Nasr; M E El-Sabban; A Mahé; R Mahieux; A Gessain; N Darwiche; G Dbaibo; J Kersual; Y Zermati; L Dianoux; M K Chelbi-Alix; H de Thé; O Hermine Journal: Leukemia Date: 2000-04 Impact factor: 11.528