Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine

Abstract

In vitro studies suggest that nucleoside analogs have an antileukemic effect against chronic myelogenous leukemia (CML). We investigated the antileukemia effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at 4 mg/m² every week for 4 weeks, then every other week for four doses, and then every month as maintenance. Two patients were in late chronic phase and two in accelerated phase. All had previously failed therapy with interferon-alpha (IFN-A). Nine patients were treated with fludarabine 30 mg/m²/day for 5 days every 28 days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were in accelerated phase and four in late chronic phase. Three patients treated with DCF had normalization of WBC counts while on the weekly schedule but progressed when changed to every other week. The fourth patient had no objective response. There were no cytogenetic responses. DCF was well tolerated with only mild nausea and vomiting in all patients. Patients treated with fludarabine received a median of two courses (range 1–4). In two patients (both Ph-positive), disease progressed to blastic phase upon recovery. Two other patients died of hemorrhagic complications secondary to thrombocytopenia. In all other cases fludarabine produced a transient reduction of WBC counts, but counts recovered to levels equal to or greater than the pre-treatment values. There were no cytogenetic responses. These results, together with previous experience with 2-CDA producing only hematologic responses, suggest that nucleoside analogs may not have a significant role in the management of CML.