We present the course of three patients suffering from chronic myelomonocytic leukemia (CMML), who presented with a markedly increase of their WBC (>200 G/l). All patients were started on chemotherapy consisting of ARA-C given as continuous infusion. Due to acute respiratory insufficiency, all patients were treated in the ICCU with ventilation support. Respiratory insufficiency was most likely due to pulmonary leukostasis since pulmonary infection or edema were excluded by X-ray in all patients. Therapeutic leukapheresis was therefore initiated and resulted in a dramatic improvement in one patient. Two patients died due to multiorganic failure despite effective leukocyte depletion (>40%) and maximum supportive care. At the onset of symptoms, two patients had markedly elevated serum lactate levels most likely due to microcirculatory failure. Both patients died because of deteriorating sequelae of pulmonary leukostasis, however, the patient with marginally elevated serum lactate levels survived. Leukapheresis is an established therapeutic approach in patients with hyperleukocytosis and leukostasis, which improves the prognosis of high-risk patients. In our opinion, patients presenting with asymptomatic hyperleukocytosis may benefit from early leukapheresis, particularly when increasing serum lactate levels indicate the early onset of microcirculatory failure.