Reduction of pulmonary toxicity by prednisolone prophylaxis during all-trans retinoic acid treatment of acute promyelocytic leukemia. Australian Leukaemia Study Group.
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 cell count (WBC). The efficacy of oral corticosteroid for prophylaxis against pulmonary toxicity has been investigated in a prospective multi-center study. ATRA was administered at 45 mg/m2/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 patients in whom the WBC rose above 10 x 10(9)/l. Combination chemotherapy plus prednisolone was added to ATRA in six other patients on the basis of criteria specified in the protocol. All 19 patients who received ATRA without chemotherapy achieved CR without signs of pulmonary toxicity despite a rise in WBC to peak values as high as 112 x 10(9)/l. Pulmonary toxicity developed in two patients commenced on ATRA in association with an unusually rapid increment in WBC of 7.5 x 10(9)/l and 32.5 x 10(9)/l in the first 2 days; both were subsequently treated with chemotherapy. The low incidence of pulmonary toxicity in this study compared with that in previous trials suggests that prednisolone prophylaxis increases safety of ATRA therapy in APL irrespective of the peak WBC.
Wiley
J S
JS
ALSG Trial Centre, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia.
Firkin
F C
FC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007958:Leukocyte Count / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012074:Remission Induction; D014212:Tretinoin / Q000009:adverse effects* / Q000627:therapeutic use*
D014212:Tretinoin; D011239:Prednisolone