Acute toxicity

The major acute toxicity of 2-CdA is myelosuppression. In their long-term follow-up study, investigators at Scripps Clinic noted a 16% incidence of Grade 3 and a 71% incidence of Grade 4 neutropenia in the first 135 consecutive treated patients.5 Ten percent had Grade 3 and 10% had Grade 4 thrombocytopenia. Grade 3 anemia occurred in 20% and Grade 4 in 2%. Forty-two percent developed neutropenic fever, though in only 13%, was an infection documented. Of these, the most common infecting organism was Staphylococcus, usually associated with the indwelling intravenous catheter. Although there were several oral herpetic infections and acute dermatomal herpes reactivations, no fungal infections were found. This high rate of neutropenia with culture negative neutropenic fever was also noted at similar rates in other single-institution series with 2-CdA. Despite the frequency of myelosuppression, additional acute toxicities were uncommon. There were no significant rates of nausea, vomiting, alopecia, myalgias, neuropathy, or allergic reactions.

Given the high rate of febrile neutropenia following cladribine therapy for hairy cell leukemia, Saven et al. studied the efficacy of filgrastim priming, followed sequentially by 2-CdA and later by daily filgrastim at 5 ^g/kg until an ANC of >2 X 109/L for two consecutive days was achieved.17 Even though the median nadir ANC increased significantly over historical controls, and the median number of neutropenic days was 9 (compared to 22 among historical controls), no significant improvement in the percentage of febrile patients, number of febrile days, or hospitalization rates for febrile neutropenia was observed.

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