Outcome of Acute Myeloid Leukemia Patients with Hyperleukocytosis in Brazil.

Acute myeloid leukemia (AML) with a high white blood cell (WBC) count at presentation has been associated with an increase early mortality rate, usually secondary to leukostasis. However, the level at which an elevated WBC count has prognostic significance in AML remains unknown. The efficiency of supportive treatments to reduce early death (ED) is also unclear. We only found few references in literature regarding hyperleukocytosis as prognostic factor in AML, and all of them concerning European and North American populations. In Brazil, we did not find any study correlating hyperleukocytosis with early death or overall survival.

We reviewed the data of 187 consecutive patients with AML treated at our institution between January 1998 and June 2008. Patients with acute promyelocytic leukemia, blastic crisis in chronic myelocytic leukemia or pediatric patients (age under 15) were excluded from the analysis.

There were 97 (52%) men and 90 (48%) women with a median age of 51 years (range 15-86). The overall survival (OS) of the total population was 115 days (range 0-2,627). The outcome of 40 patients with WBC above 50 × 10⁹L⁻¹ (hyperleukocytosis) was compared to 147 patients with a leukocyte count lower than 50 × 10⁹L⁻¹. The group with hyperleukocytosis when compared with the other group showed a significantly shorter OS, 30 (range 0-1,425) versus 150 (range 1-2,627) days (p<0.0001) and a higher rate of ED (defined as death within the first 7 days of diagnosis), 10 (25%) versus 8 (5.4%) (p=0.0008), respectively. It was noticed that when the ED data was removed from analysis, we continued observing a shorter OS in patients with hyperleukocytosis (p=0.0049), which suggests that high WBC count influences long-term survival, and not only ED. We also observed higher LDH and creatinine levels in the group of patients with hyperleukocytosis (p=0.0003 and 0.0406, respectively). The presence of liver/spleen enlargement and CNS involvement were also more frequent in the group with hyperleukocytosis (p=0.0259 and 0.0356, respectively). Besides considering all the patients with ED, we could observe higher levels of lactic dehydrogenase, a serum creatinine and nitrogen urea (p=0.0056, p=0.0008 and p<0.0001, respectively). Pulmonary involvement was more frequent in patients with ED (p=0.0277). There was no difference in frequency of hyperleukocytosis when we divided the population of patients into 2 groups according to age, about 60 years (p=0.7278).

In this study we showed that hyperleukocytosis, corresponding to more than 20% of AML patients at presentation, is an important predictive factor of ED in AML, even considering the finding that OS at our institution is poorer than previously reported by others. Among our patients with hyperleukocytosis, 25% died within the first 7 days with a suggestive clinical picture of leukostasis. Furthermore, removing the data of all ED patients from the analysis, the OS remained significantly shorter in the group with hyperleukocytosis. This fact indicates that high leukocyte count is a biological marker of somber prognosis irrespective of early complications as leukostasis. Other biological variables were associated with elevated WBC count and poorer prognosis, such as hepatosplenomegaly, CNS involvement, higher levels of lactic dehydrogenase and impaired renal function. Considering all these findings we believe that it is important to improve risk stratification for AML patients in order to develop more accurate treatment strategies.

No relevant conflicts of interest to declare.