Management of Extreme Leukocytosis

Diagnostic Approach and Initial Management

The European Society for Medical Oncology recommends monitoring for tumor lysis syndrome with frequent laboratory tests (uric acid, potassium, phosphorus, calcium, renal function) in patients with extreme leukocytosis 1
Rasburicase may be considered for prevention of hyperuricemia and renal insufficiency, although data is insufficient for a firm recommendation 1, 2
The European Society for Medical Oncology suggests that emergency leukapheresis is indicated only if there are clinical signs of leukostasis (neurological, respiratory, or hypoxia symptoms) and should be coordinated with the initiation of chemotherapy 1, 2
The National Comprehensive Cancer Network recommends that a complete diagnostic workup, including bone marrow aspiration and biopsy, should be performed immediately if acute leukemia is suspected 1, 2

The European Society for Medical Oncology recommends induction chemotherapy with an anthracycline and cytarabine (the "3+7" regimen) once all diagnostic material has been obtained for patients with non-promyelocytic acute myeloid leukemia (AML) 1, 2, 3
The European Society for Medical Oncology suggests that the initiation of treatment can be safely delayed for several days in most patients with AML until all diagnostic material has been collected and molecular typing results are available 1, 2

The European Society for Medical Oncology recommends echocardiography and assessment of cardiac risk factors at diagnosis, especially before anthracyclines 1, 2, 3
The European Society for Medical Oncology suggests that investigation for active infection with clinical examination, CT scans, and radiologic imaging of teeth and mandibles should be performed to identify infectious foci 1, 2
The European Society for Medical Oncology recommends considering delay of chemotherapy until infection has been treated in patients with active infection planned for intensive treatment 1, 2

The European Society for Medical Oncology recommends not assuming malignancy in all cases of extreme leukocytosis, as it can be a leukemoid reaction secondary to severe infection or other conditions 1, 2
The European Society for Medical Oncology suggests that HLA typing of the patient and first- and second-degree relatives should be performed at diagnosis in patients who are candidates for allogeneic transplantation 2, 3

Smoking, obesity, and asplenia are associated with leukocytosis, according to the American Society of Hematology 4
Corticosteroids are a common cause of leukocytosis, as reported by the American College of Clinical Pharmacology 4

For hyperleukocytosis (>100,000/μL), immediate aggressive intravenous hydration (2.5-3 liters/m²/day) is recommended by the American Society of Clinical Oncology 5
Hydroxyurea (50-60 mg/kg/day) may be used to rapidly reduce white blood cell counts in cases of hyperleukocytosis, as suggested by the National Comprehensive Cancer Network 5, 6
Leukapheresis may be considered in cases of symptomatic leukostasis, except in acute promyelocytic leukemia (APL), according to the American Society of Hematology 5, 6

In patients with suspected acute leukemia, prompt initiation of definitive therapy is essential, as recommended by the European Society for Medical Oncology 6
For patients with hyperleukocytosis due to APL, leukapheresis should be avoided due to the risk of fatal hemorrhage, as warned by the International Society on Thrombosis and Haemostasis 4, 7, 6
In patients with chronic myelomonocytic leukemia (CMML), rapidly increasing WBC (>10,000/μL within ≤3 months) may indicate disease progression requiring reassessment, according to the European Hematology Association 8

The European Society for Medical Oncology recommends induction chemotherapy for chronic myeloid leukemia, typically including an anthracycline and cytarabine 9, 10
The European League Against Rheumatism notes that leucocytosis is common in adult-onset Still's disease, often with striking neutrophilia, and treatment should be directed at the underlying inflammatory condition 11

The European Society for Medical Oncology advises monitoring for tumor lysis syndrome in patients with suspected acute leukemia and hyperleukocytosis, and considers rasburicase to prevent hyperuricemia and renal failure in high-risk patients 12