Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.
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.
Ratner
Lee
L
Division of Oncology, Washington University School of Medicine, St Louis, Missouri, USA. lratner@im.wustl.edu
Harrington
William
W
Feng
Xuan
X
Grant
Christian
C
Jacobson
Steve
S
Noy
Ariela
A
Sparano
Joseph
J
Lee
Jeannette
J
Ambinder
Richard
R
Campbell
Nancy
N
Lairmore
Michael
M
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
D000998:Antiviral Agents; D012367:RNA, Viral; D012321:DNA-Directed RNA Polymerases