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Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell lymphoma/leukaemia (ATLL) and patients with ATLL develop immunodeficiency due to the malignant proliferation of T-cells. Consequently, patients become more sensitive to various infectious diseases as the malignant stage advances. Cytomegalovirus (CMV) retinitis is an example of such an infectious disease that is only transiently responsive to treatment with ganciclovir and the cure rate remains very low. Foscarnet, a recently developed drug, has been a focus of clinical interest as it was effective against CMV retinitis that developed in patients with acquired immunodeficiency syndrome (AIDS) and was relatively less toxic to the marrow ( Studies of Ocular Complications of AIDS Research Group, 1992). Here, we report a case of successful treatment of CMV retinitis with foscarnet in a patient with ATLL who had been previously treated with ganciclovir. The antiviral drugs, especially foscarnet, not only improved the disease feature of CMV retinitis, but also induced leukaemic remission, followed by disappearance of leukaemic cells from peripheral blood.

The patient was a 38-year-old male. The white blood cell count (WBC) at diagnosis of ATLL was 95.6 × 109/l, with 86.5% ATLL cells, which were double positive for CD4 and CD8. Following oral administration of etoposide and prednisolone, the WBC count declined to 65.9 × 109/l, and remained at that level. 4 months after the initiation of chemotherapy the patient presented with CMV retinitis. Following treatment with ganciclovir (500 mg/d) the retinitis lesion gradually subsided. As the patient underwent stepwise decreases in the dosage of ganciclovir, the CMV retinitis relapsed. Subsequent re-increase in the dosage of ganciclovir resulted in the development of leucocytopenia (0.6 × 109/l, with 1.0% ATLL cells) and thrombocytopenia (81 × 109/l). Therefore ganciclovir was discontinued and foscarnet was initiated at a dose of 10 800 mg/d. Foscarnet proved effective and the signs of CMV retinitis slowly subsided. The WBC count also recovered to a level of 4.0 × 109/l accompanied by the disappearance of ATLL cells from the peripheral blood. Although the patient had not received specific treatment for ATLL from the initiation of ganciclovir chemotherapy to the time of this report, 8 months after discontinuation of foscarnet chemotherapy, WBC count remained at a level of 4.0 × 109/l without detectable ATLL cells. The incidence of CD4+8+ double-positive T cells was 0.2%. HTLV-1-associated proteins were detected in the patient's serum and the viral sequence of HTLV-1 was also detected in the peripheral mononuclear cells by PCR. However, monoclonal integration of HTLV-1 proviral DNA into the peripheral mononuclear cells was no longer detected by Southern blot analysis. Taken together, treatment with antiviral drugs, especially foscarnet, seemed to have pushed back the disease phase in this patient to an HTLV-1 carrier state or the early stage of ATLL development.

Although it is not clear how the antiviral agents exerted their antileukaemic activity in our case, foscarnet is known to act directly on the replication of human immunodeficiency viruses (HIV) in vitro ( Eriksson & Schinazi, 1989). Treatment with foscarnet in patients with AIDS induced a decrease in viral p24 antigen ( Jacobson et al, 1991 ; Reddy et al, 1992 ) and was effective in improving the survival rate. Our findings suggest that some antiviral agents including foscarnet may act on HTLV-1 and clinically exert an antileukaemic action in ATLL.

References

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  2. References
  • 1
    Eriksson, B. & Schinazi, R.F. (1989) Combinations of 3′-azido-3′-deoxythimidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro. Antimicrobial Agents and Chemotherapy, 33, 663 669.
  • 2
    Jacobson, M.A., van der Horst, C., Causey, D.M., Dehlinger, M., Hafner, R., Mills, J. (1991) In vitro additive antiretroviral effect of combined zidovudine and foscarnet therapy for human immunodeficiency virus infection (ACTG protocol 053). Journal of Infectious Diseases, 153, 1219 1222.
  • 3
    Reddy, M.M., Grieco, M.H., McKinley, G.F., Causey, D.M., van der Horst, C.M., Parenti, D.M., Hooton, T.M., Davis, R.B., Jacobson, M.A. (1992) Effect of foscarnet therapy on human immunodeficiency virus p24 antigen levels in AIDS patients with cytomegalovirus retinitis. Journal of Infectious Diseases, 166, 607 610.
  • 4
    Studies of Ocular Complications of AIDS Research Group (1992) Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. New England Journal of Medicine, 326, 213 220.