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.
  
  
  RESULTS
  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.
authors.affiliation: Division of Oncology, Washington University School of Medicine, St Louis, Missouri, USA. lratner@im.wustl.edu
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.forename: William
authors.initials: W
authors.lastname: Harrington
authors.forename: Xuan
authors.initials: X
authors.lastname: Feng
authors.forename: Christian
authors.initials: C
authors.lastname: Grant
authors.forename: Steve
authors.initials: S
authors.lastname: Jacobson
authors.forename: Ariela
authors.initials: A
authors.lastname: Noy
authors.forename: Joseph
authors.initials: J
authors.lastname: Sparano
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Ambinder
authors.forename: Nancy
authors.initials: N
authors.lastname: Campbell
authors.forename: Michael
authors.initials: M
authors.lastname: Lairmore
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D008875:Middle Aged; D012367:RNA, Viral / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012321:DNA-Directed RNA Polymerases