The Combination of Zidovudine and Interferon AIpha-2B in the Treatment of Adult T-Cell Leukemia/Lymphoma

Abstract

Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and interferon alpha (IFNalpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNalpha-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times a day) and IFNalpha-2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received.

Telomere attrition induces a DNA double-strand break damage signal that reactivates p53 transcription in HTLV-I leukemic cells

“…Antiviral therapy with zidovudine (AZT) and interferon-alpha (IFN-a) in these patients has produced longterm clinical remissions in human trials (Gill et al, 1995;Hermine et al, 1995;Matutes et al, 2001;White et al, 2001). In HTLV-I-infected cells, Tax stimulates endogenous hTERT promoter (Sinha-Datta et al, 2004).…”

Quantification of HTLV-1 reverse transcriptase activity in ATL patients treated with zidovudine and interferon-α

“…[9][10][11] The efficacy of this combination was confirmed, with minor differences, in various clinical trials and in a worldwide meta-analysis. [12][13][14][15][16] These results changed the clinical management of ATL. [16][17][18][19] However, there is yet no direct proof of an antiviral mechanism of action of the drug combination, due to the absence of virological markers that strictly correlate with disease status.…”

Treatment of Adult T-cell Leukemia

“…[64][65][66][67][68][69] Gill et al in the United States reported that treatment with AZT/IFN produced an objective response in 11 (five CR, six PR) of 19 patients with acute or lymphoma type ATL, 64 while a French group reported that the regimen produced an objective response in all five ATL patients that they treated. 65 Although the results with AZT/IFN are encouraging, the overall survivTreatment of ATL al of previously untreated ATL patients was rather short (4.8 mon) 66 when compared to those on the LSG15 regimen.…”