Apl Differentiation Syndrome

The pathophysiology and treatment of RA syndrome or "APL differentiation syndrome" have recently been reviewed,45 46 and knowledge of the manifestations of this potentially fatal complication of induction therapy is essential to all clinicians who treat APL. The most common presenting symptoms47-49 are respiratory distress, fever, pulmonary infiltrates, weight gain, and pleural/pericardial effusions. Less common signs and symptoms include renal failure, cardiac failure, hypotension, and bone pain. These symptoms can develop at virtually any time after presentation (and may be present before any therapy), but the median time to development is between weeks 1 and 2 after the start of induction.47-49 The differential diagnosis includes sepsis/acute respiratory distress syndrome, as well as pulmonary hemorrhage, and the outcome can be fatal if the disorder is not recognized, diagnosed correctly, and properly treated. Treatment of RA syndrome is with corticos-teroids (given at the earliest time possible), generally dexamethasone 10 mg q 12 h, and temporary discontinuation of ATRA, at least in severe cases. ATRA can (and should) be safely restarted after the syndrome resolves, and RA syndrome is exceedingly rare in patients who receive ATRA during consolidation or maintenance phases of their treatment. Thus, there should be no hesitation in subsequent use of ATRA in patients who may have developed RA syndrome during induction. The incidence of RA syndrome seems to be lower in patients who receive combined ATRA/chemotherapy induc-tion,47 and it may be lower in patients who receive prophylactic steroids, but it is clearly not "a problem of the past" and remains a significant clinical issue in the treatment of APL.46 Finally, note that APL differentiation syndrome also occurs in patients treated with arsenic tri-oxide for newly diagnosed or relapsed APL,50 and approximately 50% of such patients develop leukocyto-sis, which can be marked. In general, the leukocytosis is self-limiting and does not require therapy, but patients with leukocytosis who develop symptoms or signs of coexistent APL differentiation syndrome require treatment with corticosteroids.50

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