Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma Journal Article
| Authors: | Ratner, L.; Harrington, W.; Feng, X.; Grant, C.; Jacobson, S.; Noy, A.; Sparano, J.; Lee, J.; Ambinder, R.; Campbell, N.; Lairmore, M. |
| Article Title: | Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma |
| Abstract: | Background: 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. Methods and Findings: 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. Conclusions: 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. © 2009 Ratner et al. |
| Keywords: | adult; clinical article; treatment outcome; disease-free survival; middle aged; prednisone; clinical trial; disease course; doxorubicin; cancer combination chemotherapy; dose response; drug efficacy; disease free survival; metabolism; disease association; multiple cycle treatment; phase 2 clinical trial; etoposide; cyclophosphamide; vincristine; pneumocystis pneumonia; continuous infusion; drug effect; pathology; physiology; time; time factors; virology; t cell lymphoma; virus rna; disease progression; remission; antivirus agent; human immunodeficiency virus; virus replication; alpha2a interferon; drug dose regimen; drug treatment failure; cotrimoxazole; granulocyte colony stimulating factor; t cell leukemia; dapsone; pentamidine; drug dose sequence; rna, viral; virus reactivation; zidovudine; human t cell leukemia virus 1; human t-lymphotropic virus 1; leukemia-lymphoma, adult t-cell; dna directed rna polymerase; dna-directed rna polymerases; lamivudine; lamivudine plus zidovudine; antiviral therapy; human t cell leukemia virus; human t cell leukemia virus infection; virus expression; virus activation; antiviral agents |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 2 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-02-10 |
| Start Page: | e4420 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0004420 |
| PUBMED: | 19204798 |
| PROVIDER: | scopus |
| PMCID: | PMC2636875 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "Art. No.: e4420" - "Source: Scopus" |
