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Acute promyelocytic leukemia (APL) is generally held to have favorable risk, but we have observed a high incidence of early deaths caused by fatal bleeding and differentiation syndrome (DS). We retrospectively analyzed 259 APL patients from 2002 to 2014 who all received all-trans retinoic acid (ATRA) with the support of sufficient transfusions, followed by 4 days of idarubicin. High-risk status was determined as a diagnostic leukocyte count (WBCdx) >10 × 10 9 /L (Sanz criteria). For patients with hyperleukocytosis, we sometimes conducted leukapheresis and also used hydroxyurea and prophylactic dexamethasone. Because we frequently observed patient fatalities from progressive hyperleukocytosis, we also checked the maximum leukocyte count (WBCmax) and stratified patients by their incremental ratios. The 8-week cumulative incidence of early death and DS was 13.5% and 17.8%, respectively. We found that WBCmax correlated better with early death and DS, even in the low-risk group, than WBCdx. Among the patients with WBCdx <10 × 10 9 /L, a WBCmax >43 × 10 9 /L correlated with early death (26.7%) and DS (40.0%). Also, having a WBCdx of 10 to 43 × 10 9 /La that increased to a WBCmax >43 × 10 9 /L correlated with increased early death (33.3%). The multivariate analysis revealed that a WBCmax >43 × 10 9 /L correlated significantly with both early death and DS.

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Progressive hyperleukocytosis is a relevant predictive marker for differentiation syndrome, early death, and subsequent relapse in acute promyelocytic leukemia