2-Chlorodeoxyadenosine (cladribine)-related eosinophilia in patients with lymphoproliferative diseases

Abstract

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.