A novel <i>AF10‐CALM</i> fusion transcript in γ/δ‐T cell type lymphoblastic lymphoma
Authors: Eishi Ashihara, Shigeo Nakamura, Tohru Inaba, Tomohiko Taki, Yasuhide Hayashi, Chihiro Shimazaki
Journal: American Journal of Hematology (2007)

Experience with oral interferon-alpha in patients with essential thrombocythemia and polycythemia veraTo the Editor: Prolonged subcutaneous interferon-alpha (IFN-) therapy frequently results in high drop-out rates because of toxicity [1].IFNadministered through the oromucosal route at doses ranging between 37.5 and 150 IU thrice daily [2,3] has resulted in significant responses with minimal toxicity in patients with Sjo ¨gren's syndrome [2] and hepatitis B [3].We designed a pilot trial to evaluate the efficacy and tolerability of oral IFN-for patients with essential thrombocythemia (ET) or polycythemia vera (PV).Patients were eligible if they refused to take, had failed, or were intolerant to standard medications.Failure to respond to standard medications was defined as, for ET, inability to reduce platelets to normal levels after a minimum of 6 months of therapy with hydroxyurea and/or anagrelide, and for PV, as inability to reduce by at least 50% the frequency of phlebotomy or splenomegaly after a minimum of 6 months of therapy with hydroxyurea.Prior IFN-exposure was not allowed.Oral IFN-was administered at 150 IU thrice daily as a lozenge to 14 patients (8 PV and 6 ET).Median age was 57 years (range, 32-79), time from PV/ET diagnosis to oral IFN-therapy was 2 months (range, 0-32), hemoglobin 14.2 gm/dL (range 11.2-15.4),white blood cells 9.75 Â 10 9 /L (range 5.6-17.3),and platelets 812 Â 10 9 /L (range, 360-1,389).Five patients previously received hydroxyurea, four anagrelide, and three imatinib mesylate.Six PV patients had received phlebotomies and two had marked splenomegaly.JAK2 V617F mutation was detected in 10 (91%) of 11 assessable patients; 2 (14%) of 14 had abnormal cytogenetics.A total of 16 cycles were administered.The median duration of therapy was 3 months (range, 2.5-6).Thirteen patients discontinued therapy because of lack of a response, and one due to disease progression.Tolerance of oral IFN-was excellent.All reported toxicities were Grade 1: headache in two, and paresthesias in one patient.IFN-is a protein and, therefore, it is not considered to be orally bioavailable owing to rapid denaturation upon contact with gastric secretions [4].To bypass this hindrance, patients were required to keep the lozenges in the mouth until they completely dissolved to maximize oral absorption.The actual absorption of oral IFN-in humans, however, is questionable, since no IFN-receptor has been isolated in the buccal mucosa [4].Furthermore, studies in different animals and healthy human volunteers have shown that IFN-administered orally was extremely rarely detected in the blood [5].Yet, the administration of IFN-via the oromucosal route has been shown to exert significant systemic antitumoral and immunomodulatory effects through the activation of gene transcription in the lymphoid tissue of the oropharyngeal cavity [5].The dose of oral IFN-used in our study was deemed optimal based on prior reports [2,5].In conclusion, oral IFN-at 150 IU thrice daily for patients with PV or ET is very safe but renders no appreciable clinical benefit.