Complications Of Induction Therapy

The vast majority of APL patients who fail induction do so not because of resistant disease, but because of fatal hemorrhage [usually central nervous system (CNS)], retinoic acid (RA) syndrome (also called "APL differentiation syndrome"), or infection. Rates of early death are, at least historically, much higher in patients with high WBC counts,29'32'36 as high as 24% in some studies. The Spanish Group has reported an early death rate of 8.4% in 642 patients treated with simultaneous ATRA and idarubicin (AIDA) between 1996 and 2003 in two successive studies36; 58% of the early deaths were due to hemorrhage, 31% due to infection, and 10% due to RA syndrome.36 The rate of early death did not decrease in the more recent LPA99 study, despite the prophylactic use of prednisone (to prevent RA syndrome) and tranexamic acid (to improve the coagulopathy). Renal dysfunction (creatinine >1.4 mg/dL) and high WBC count (>10,000) were the only independent predictors of early death. It is

Table 6.1

Outcomes of therapy for APL in the "ATRA era"

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