2 Chlorodeoxyadenosine (2-CdA) and Cytarabine (ara-C) Combination Is Effective and Safe in Idiopathic Hypereosinophilic Syndrome (HES).

Hypereosinophilic syndrome (HES) is rare, disabling, and incurable disease. In a pilot study, the combination of 2-CdA and ara-C chemotherapy has been evaluated in 9 patients. The median time from diagnosis to therapy was 25 months. All patients had signs and symptoms of end-organ involvement. Seven patients received prior therapies. The median eosinophil count at presentation was 14 x10⁹/L (0.3–110 x10⁹/L) and the median percent eosinophilic bone marrow infiltration was 23% (6%–43%). Ara-C (1g/m²) was given intravenously over 2 hours at hours 0, 48, 72, 96, and 120; 2-CdA (12 mg/m²/day) was given as continuous infusion intravenously over 5 days starting at 24 hours. A second course at the same level was administered for patients who achieved complete remission (CR) and for patients who had >50% reduction in eosinophilic infiltration. Two patients studied for pharmacokinetics of ara-CTP (active metabolite of ara-C) in the circulating blood cells accumulated either similar or higher levels of ara-CTP after infusion of 2-CdA. Five patients (55%) achieved CR, one requiring 2 cycles. Elimination of eosinophilia was accompanied by the resolution of symptoms. The median disease free survival was 26 months; 1 patient remains disease free (after allogeneic transplantation) at 42 months. The median overall survival from diagnosis for CR patients was 44 mo. Treatment was well tolerated. Febrile neutropenia occurred in 28% of the 14 cycles given. The median time to recovery from neutropenia and thrombocytopenia was 17 and 39 days, respectively. There was one death related to disease progression. We conclude that 2-CdA + ara-C combination regimen is safe alternative therapy for HES. The addition of consolidation therapy or imatinib may improve the results.