ALPHA‐INTERFERON THERAPY IN REFRACTORY ANGIOIMMUNO‐BLASTIC LYMPHADENOPATHY

To the Editor: Angioimmunoblastic lymphadenopathy is a rare disorder first described by Frizzera (1) in 1974. A very extensive review of the disease was carried out in 1985 (2) . Except for cases of spontaneous remission, the clinical evolution is generally severe despite chemotherapy, with a median survival of about 18 months. Recently, the analysis of the beta chain of the T-cell receptor indicates that a monoclonal T-cell proliferation is present in more than 85% of cases of angioimmunoblastic lymphadenopathy (3, 4). We report here the case of a 67-yr-old man who presented in January 1985 with weight loss, arthralgia of the hands, night sweats, fever, cough and skin rash. 3 months later, he developed generalized lymphadenopathies, splenomegaly and purpura. His biological picture was: E.S. R.111 mm/h, W.B.C. 1486O/pl, apolyclonal hypergammaglobulinemia and a positive Coombs test. Axillary lymph-node biopsy was performed and exhibited the typical pattern of angioimmunoblastic lymphadenopathy. The histological diagnosis was confirmed by Pr. J . Diebold (Paris). A bone marrow aspiration was normal. The clinical evolution was unfavourable despite 60 mg prednisolone/d for 2 months. The patient then received a CVP chemotherapy that was accompanied by a complete clinical and biological resolution, with correction of the thrombocytopenia. After 5 cycles, a recurrence of all the constitutional symptoms required another course of chemotherapy (CHOP 6 cycles) and the patient entered a new complete remission. He remained free of symptoms with no maintenance treatment for 6 months. Then a second recurrence was characterized by fever, rash, splenomegaly, a slight axillary lymphadenopathy, presence of circulating atypical lymphocytes, but absence of thrombocytopenia, a negative Coombs test and a normal bone marrow aspiration. The disease became resistant to corticoids, cyclophosphamide and teniposide and his clinical condition rapidly worsened. Therapy with interferon alpha 2-b (Schering) 5 x lo6 I.U. SC 3 times a week was begun. After 2 wk, the lymphadenopathy, the constitutional symptoms and the splenomegaly had disappeared. His general condition improved but the platelet count dropped gradually to 30 OOO/pI. Interferon therapy was interrupted because of pancytopenia after 2 months. At this time, bone-marrow aspiration showed an aplastic pattern without immunoblasts or other abnormal cells. The platelet count increased after 6 wk without treatment and the patient was again in clinical remission. The mode of action of alpha-interferon in haematologic malignancies is composite: direct antiproliferative effects, immunomodulatory activities and inhibition of oncogene expression (5). The role of antiviral activity remain to be elucidated in light of virological investigations focused on HTLV-I, HTLV-I1 and the new isolate HBLV (6). In the present case, a hypothetical mechanism centred on oncogene expression seems to us to be attractive. Indeed, the use of low doses of interferon does not favour direct antiproliferative activity. Moreover, the modulation of c-fos oncogene expression by alphainterferon is well known in hairy-cell leukaemia (7) and we found very striking the recent study (8) concerning abnormalities of N-ras and c-fos oncogenes expression in angioimmunoblastic lymphadenopathy, which may be corrected by cyclophosphamide.