Long-term clinical remission maintained after cessation of zidovudine and interferon-α therapy in chronic adult T-cell leukemia/lymphoma
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Globally, > 5–10 million people are estimated to be infected with Human T-lymphotropic virus type 1 (HTLV-1), of whom ~ 5% develop adult T-cell leukemia/lymphoma (ATL). Despite advances in chemotherapy, overall survival (OS) has not improved in the 35 years since HTLV-1 was first described. In Europe/USA, combination treatment with zidovudine and interferon-α (ZDV/IFN-α) has substantially changed the management of patients with the leukemic subtypes of ATL (acute or unfavorable chronic ATL) and is under clinical trial evaluation in Japan. However, there is only a single published report of long-term clinical remission on discontinuing ZDV/IFN-α therapy and the optimal duration of treatment is unknown. Anecdotal cases where therapy is discontinued due to side effects or compliance have been associated with rapid disease relapse, and it has been widely accepted that the majority of patients will require life-long therapy. The development of molecular methods to quantify minimal residual disease is essential to potentially guide therapy for individual patients. Here, for the first time, we report molecular evidence that supports long-term clinical remission in a patient who was previously treated with ZDV/IFN-α for 5 years, and who has now been off all therapy for over 6 years.
KeywordsZidovudine/interferon-α Chronic ATL HTLV
The authors are grateful to Dr. Catherine E. Hoggarth, Consultant Haematologist at Hinchingbrooke Hospital, Cambridgeshire, for her clinical support in the management of this patient. The authors are also extremely grateful to the clinical staff at the National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, London, U.K and Laurence Game, MRC Genomics Facility, Imperial College London. The research was supported by Wellcome Trust (CRMB Senior Investigator Award, ref. WT100291MA), the Medical Research Council (ref. MR/K019090/1) and the Imperial National Institute for Health Research Biomedical Research Centre and the Imperial College Communicable Diseases Research Tissue Bank.
LBC and AGR contributed equally to the manuscript including concept, design and drafting of the article and figures. MAD and CG undertook molecular PVL monitoring; SJS and AGR clone specific qPCR and analysis; LMPCR was performed by LBC, AGR, NAG, AW and analyzed by LBC, AGR, NAG, AM. CRMB and GPT contributed to the concept and design, drafting of the article and critical revision. All authors have given final approval of the version to be published.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest. LBC reports consultancy fees from Kyowa Hakko Kirin pharma, outside the submitted work. GPT reports other fees from Imperial NIHR BRC during the conduct of the study; Grants from Bloodwise, Grants from Wellcome Trust, Grants from MRC, outside the submitted work.
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