Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma

Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epi...

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Bibliographic Details
Published in:	PloS one 2009-02, Vol.4 (2), p.e4420-e4420
Main Authors:	Ratner, Lee, Harrington, William, Feng, Xuan, Grant, Christian, Jacobson, Steve, Noy, Ariela, Sparano, Joseph, Lee, Jeannette, Ambinder, Richard, Campbell, Nancy, Lairmore, Michael
Format:	Article
Language:	eng
Subjects:	Activation Adult Anthracyclines Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Biological response modifiers Blood & organ donations Bone marrow Cancer Cancer therapies Chemotherapy Clinical trials Corticosteroids Cyclophosphamide Development and progression Disease Disease Progression Disease-Free Survival DNA-Directed RNA Polymerases - metabolism Doxorubicin Drug therapy Epigenetic inheritance Etoposide Gene expression Genes Health aspects Health care facilities Hematology Highly active antiretroviral therapy Human T-lymphotropic virus 1 - drug effects Human T-lymphotropic virus 1 - physiology Humans Immunotherapy Infectious Diseases/Viral Infections Interferon Interferon alpha Lamivudine Leukemia Leukemia-Lymphoma, Adult T-Cell - drug therapy Leukemia-Lymphoma, Adult T-Cell - pathology Leukemia-Lymphoma, Adult T-Cell - virology Lymphocytes Lymphocytes T Lymphoma Lymphomas Medical centers Medical colleges Medical research Medical services Medicine, Experimental Middle Aged Neurological disorders Non-Hodgkin's lymphomas Oncology Oncology/Hematological Malignancies Pathogenesis Patients Prednisone Prevention Prognosis Ribonucleic acid RNA RNA, Viral - metabolism Stroke T cell receptors T cells Time Factors Toxic diseases Toxicity Transplants & implants Treatment Outcome Trends Veterinary colleges Veterinary medicine Vincristine Virology Virology/Viruses and Cancer Virus Activation - drug effects Viruses Zidovudine α-Interferon
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Summary:	Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis. We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH) given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold), and virus replication occurred, coincident with development of disease progression. EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.
ISSN:	1932-6203 1932-6203