Clinical Features, Complications, and Early Treatment Outcome of Pediatric Acute Myeloid Leukemia with Hyperleukocytosis.

Patients with acute myeloid leukemia (AML) and hyperleukocytosis are at increased risk of early death from neurological and pulmonary complications due to leukostasis. Although leukapheresis is often used for rapid cytoreduction in these patients, a recent adult study showed no difference in the rate of early mortality between patients who underwent leukapheresis and historical controls. The scarcity of information about leukapheresis in childhood AML led us review our experience of 106 children with AML and hyperleukocytosis (i.e., initial leukocyte count ≥ 100 × 109/L) treated between 1968 and 2002. The presenting clinical features, early complications, and clinical outcomes during the first 2 weeks of remission induction therapy were analyzed according to two treatment eras: early (1968–1982) vs. recent (1983–2002), when leukapheresis was available. The entire cohort had a median age of 9.7 years (range, 0–19.9 years); initial leukocyte count of 161 × 109/L (100 to 1,600); hemoglobin concentration of 8.2 g/dL (2.9–15.4); and platelet count of 38.5 × 109/L (0 to 300). The presenting features were comparable between patients treated in the two eras with the exception of higher hemoglobin concentrations among those treated in the recent era (p=0.03). Platelet transfusion prior to chemotherapy was used more often in the recent era (p=0.001). Half of the cases (53 of 106) had FAB M4 or M5 subtypes. Twenty-one patients (19.8%) had grade 3 or 4 neurological, respiratory, and/or renal complications (according to NCI common criteria) at initial presentation, and 35 patients (33%) had one or more of these complications during the first 2 weeks after diagnosis (17 neurological; 20 respiratory; 16 renal). The frequency of the complications did not differ significantly between patients treated in the two eras. Patients with FAB M4/M5 AML were significantly more prone than others to respiratory (p=0.005) and renal (p=0.0002) complications during the first two weeks of therapy. Seventeen patients (16%) died during the first 2 weeks after diagnosis. The rate of early death was significantly higher in the early era than in the recent era (16/70 vs. 1/36, p=0.01). The time between admission and initiation of chemotherapy was significantly shorter (20.2 vs. 33.6 hours, p<0.0001), and the reduction of leukocyte count before chemotherapy was significantly less (−3 × 109/L vs. −77.1 × 109/L, p<0.0001) in patients treated in the early era, as compared to those from the recent era. Among patients treated in the recent era, the 20 who underwent leukapheresis had a higher initial leukocyte count (205.9 × 109/L vs. 115.5 × 109/L, p<0.0001) than the 16 who did not undergo the procedure. Although the incidence of acute complications did not differ between the two eras, the rate of early death was markedly decreased in the recent era (from 23% to 2.8%), suggesting that leukapheresis/exchange transfusion might have prevented some early deaths. Our results suggest that improved supportive care, including the use of leukapheresis, decreases early mortality caused by leukostasis, especially in patients with M4 or M5 subtypes of AML.