Prophylaxis And Treatment

Prophylactic administration of prednisolone in APL patients with WBC counts rising above 10,000/ml on treatment with ATRA prevented pulmonary toxicity despite WBC counts as high as 100,000/ml.72 This is a promising strategy, but needs to be evaluated in a larger prospective trial.

In an attempt to decrease the incidence of the differentiation syndrome, several dose modifications of ATRA have been tried. ATRA at a dose of 25 mg/m2/d did not decrease the incidence of the syndrome, but appeared to have similar efficacy as the standard dosage of 45 mg/m2/d.73 In another small study, an even lower dose of ATRA at 15-20 mg/m2/d had a lower incidence of the differentiation syndrome without compromising efficacy.74 These strategies, however, need confirmation in larger trials.

Recognition of the clinical syndrome and prompt initiation of therapy with intravenous dexamethasone 10 mg every 12 hours for three days at the first sign of fever, dyspnea, unexplained weight gain, or pulmonary infiltrates is of utmost importance. Treatment with ATRA can be continued in mild cases of the differentiation syndrome with good outcomes.66 However, ATRA should be discontinued in moderate to severe cases and may be resumed once symptoms resolve. If ATRA is resumed, close monitoring is required, as the syndrome can recur despite prophylaxis with steroids. ATRA does not appear to cause the syndrome when used in the maintenance phase. With early and aggressive treatment, the mortality of RAS in most large series is about 1%.66

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