Interferon α and zidovudine therapy in adult T‐cell leukaemia lymphoma: response and outcome in 15 patients

Abstract

Adult T‐cell leukaemia lymphoma (ATLL) is an aggressive disease caused by the human T‐lymphotropic virus 1 (HTLV‐I) with a short survival. Responses to interferon alpha (IFN‐α) and zidovudine (AZT) have been documented but not with long‐term follow‐up. We treated 15 ATLL patients with IFN and AZT. Eleven patients had acute ATLL, two had lymphoma and two smouldering ATLL, with progression. The main features were: organomegaly (14), skin lesions (10), high white blood cell (WBC) count (11) and hypercalcaemia (9). Eleven patients had previously received chemotherapy and one had received an autograft. At the time of the study, seven patients had progressive disease and eight were in partial or complete clinical remission. Responses (PR) lasting 2+ to 44+ months were seen in 67%; 26% did not respond (NR) and one patient was not evaluable. Hypercalcaemia predicted a poor outcome but differences were not significant. Eight of the 15 patients have died 3–41 months from diagnosis. Median survival for the 15 patients was 18 months. Survival of the NR ranged from 4 to 20 months; six PR patients are alive 8–82 months from diagnosis. The differences in survival between NR (median: 6 months) and PR (55% of patients alive at 4 years) were statistically significant (P = 0·002). In conclusion, IFN and AZT improves the outcome of ATLL patients and helps maintain responses.

Epidemiology, clinical features, and outcome of HTLV-1–related ATLL in an area of prevalence in the United States

“…12 Phase 2 studies performed outside of Japan, including at our center, have demonstrated the efficacy of zidovudine and interferon-a (AZT-IFN) in patients with chronic and aggressive leukemic ATLL types. [13][14][15] A recent retrospective multicenter analysis suggested that AZT-IFN may be more effective in leukemic ATLL forms in terms of long-term outcome, as several patients with acute type remained progression-free under maintenance therapy for several years. 16 AZT-IFN is now considered a first-line treatment option for nonlymphomatous ATLL 17 and is recommended under National Comprehensive Cancer Network treatment guidelines.…”

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).…”

Natural history of adult T-cell leukemia/lymphoma and approaches to therapy

“…In the UK, a debulking approach with 1-2 cycles of CHOP followed by a switch to lower doses of interferon-a (3-5 MU) plus zidovudine 500 mg bd was preferred. In total, 15 predominantly naı¨ve, patients were treated in an open study, 67% achieving remission (CR þ PR) with a median survival of 18 months (Matutes et al, 2001). In a further phase II study from France of 12 treatment naı¨ve patients with acute and lymphoma ATLL, the 92% response rate (seven CR and four PR) with zidovudine plus interferon-a represents a significant improvement over conventional and other chemotherapies .…”