REDUCTION OF PULMONARY TOXICITY BY PREDNISOLONE PROPHYLAXIS DURING ALL-TRANS-RETINOIC ACID TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA

All-trans retinoic acid (ATRA) induces complete remission (CR) in most cases of acute promyelocytic leukemia (APL) but its use is associated with potentially fatal pulmonary toxicity in approximately 25% of APL patients in the setting of a rapidly rising peripheral blood white ce ll count (WBC). The efficacy of oral corticosteroid for prophylaxis ag ainst pulmonary toxicity has been investigated in a prospective multi- center study. ATRA was administered at 45 mg/m(2)/day as single agent therapy throughout induction treatment in 19 patients with an initial WBC <10 x 10(9)/l, and prednisolone 75 mg/day was added in those 12 pa tients in whom the WBC rose above 10 x 10(9)/l. Combination chemothera py plus prednisolone was added to ATRA in six other patients on the ba sis of criteria specified in the protocol. All 19 patients who receive d ATRA without chemotherapy achieved CR without signs of pulmonary tox icity despite a rise in WBC to peak values as high as 112 x 10(9)/l. P ulmonary toxicity developed in two patients commenced on ATRA in assoc iation with an unusually rapid increment in WBC of 7.5 x 10(9)/l and 3 2.5 x 10(9)/l in the first 2 days; both were subsequently treated with chemotherapy. The low incidence of pulmonary toxicity in this study c ompared with that in previous trials suggests that prednisolone prophy laxis increases safety of ATRA therapy in APL irrespective of the peak WBC.