Background: Malignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands' strategy is associated with survival. Methods: We reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands' algorithm (indication and timing of specific treatments). Results: Twenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7-28] G/l/day vs 5.9 [3.0-6.8] G/l/day, p = 0.007). WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio < 1 were significantly associated with death (p = 0.001 and p = 0.003, respectively). Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands' strategy was associated with survival (100% vs 0%; p < 0.001, relative risk of death = 0.18, 95%-CI [0.05-0.64]). Conclusions: A fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands' strategy, with the expectation of a better survival.