Azothymidine and interferon-a are active in AIDS-associated small non-cleaved cell lymphoma but not large-cell lymphoma
Authors: William J Harrington Jr, Lisa Cabral, Jiang-Ping Cai, Sharon Chan-A-Sue, Charles Wood
Journal: The Lancet (1996)

HIV-1 infection is associated with the development of aggressive B-cell lymphomas. Conventional cytotoxic treatment of these tumours is often ineffective and fraught with complications such as tumour-lysis syndrome. Interferon alpha (INFa) has shown activity alone and in combination with zidovudine (AZT) in patients with Kaposi's sarcoma and adult T-cell leukaemia (ATL).1Kovacs JA Deyton L Davey R et al.Combined zidovudine and interferon-alpha therapy in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS).Ann In tern Med. 1989; 280: 111Google Scholar, 2Gill PS Harrington Jr, WJ Kaplan MH et al.Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine.NEJM. 1995; 332: 1744Crossref PubMed Scopus (308) Google Scholar, 3Hermine O Bouscary D Gessain A et al.Brief report: treatment of adult T-cell leukemia-lymphoma with zidovudine and interferon alfa.NEJM. 1995; 332: 1749Crossref PubMed Scopus (216) Google Scholar We successfully treated four patients with HIV-1-related small non-cleaved cell (SNCC) lymphoma with intravenous AZT and IFNα. Each had circulating L3 type lymphoblasts and easily measurable disease. Flow cytometry was consistent with SNCC lymphoma in two patients studied. All tumour histologies were classified by an experienced haematopathologist. All patients had an elevated lactate dehydrogenase (LDH) ranging from four to 20 times normal. Patients were treated with AZT 1-5 g intravenously twice daily and IFNa 10 million units intravenously twice daily. One patient received intravenous methylprednisolone for 2 days before starting parenteral AZT and INFa and all received intrathecal methotrexate (10 mg) and cytarabine (30 mg). Each responded with a rapid decrease in LDH (figure) and regression of tumour without complications associated with tumour-lysis (hyperuricaemia, hypo-phosphataemia). Two patients had clearance of leukaemic infiltration of their bone marrow. Three patients received a consolidation chemotherapy regimen for 12 weeks (cyclophosphamide, mitoxantrone, and etoposide alternating weekly with vincristine and bleomycin, and weekly methylprednisolone) starting on day 16. Three patients remain in remission 1,5, and 5 months since consolidation. One patient, who presented with extensive gastrointestinal involvement, responded to therapy but died of a gastrointestinal bleed on day 14. Haematological complications were controlled with G-CSF and transfusions. There were no infectious complications. The same regimen was used to treat two patients with HIV-1-related large cell immunoblastic lymphoma (LCL); there was no response and after 1 week both were treated with conventional chemotherapy. The regression of this highly aggressive lymphoma (SNCC) without tumour lysis indicates that AZT and INFa act via a mechanism distinct from standard cytotoxic chemotherapy. There is a case report documenting regression of pulmonary AIDS lymphoma after administration of oral AZT.4Baselga J Krown SE Telzak EE Filippa DA Strauss DJ Acquired immune deficiency syndrome-related pulmonary non-Hodgkin lymphoma regressing after zidovudine therapy.Cancer. 1993; 71: 2332Crossref PubMed Scopus (19) Google Scholar Preliminary data from our laboratory indicates that AZT with INFa induces retroviral leukaemic (SNCC and ATL) cell lines to enter apoptosis. The fact that antivirals, by themselves, have such pronounced activity against one of the most aggressive malignant diseases known is provocative.