Subacute pulmonary failure complicating therapy with high-dose Ara-C in acute leukemia

Seventy-four adult patients with acute leukemia in relapse were studied. They received high-dose intravenous boluses of cytosine arabinoside (Ara-C) according to the following schedules: 3 g/m2 over 2 hours, every 12 hours for 4 to 12 consecutive doses, or a continuous infusion over 5 days at 200, 400, or 800 mg/m2/day. The patients' ages ranged from 16 to 68 years (median, 35). Subacute pulmonary failure attributable to Ara-C was observed in 16 of 72 evaluable patients (22%) and appeared 2 to 21 days (median, 6) after the first dose. None of the 28 patients who received up to six doses experienced any toxicity. With repeated courses or more than six doses in the first course there was a sharp increase in the incidence of toxicity. Thus, subacute pulmonary failure developed in 6 of 24 patients who received 9 doses and 6 of 19 patients who received 12 doses. The increase in toxicity with increasing number of doses is significant (P = 0.03). This suggests that the high-dose Ara-C regimen should be used with awareness of possible drug-induced pulmonary toxicity.