Hyperleukocytosis

Definitions ✍️

• Leukemoid Reaction: absolute WBC count >50,000 cells/µL (ie >50.0 cells x 1000/µL), majority of those cells being mature neutrophils & often accompanied by prominent left shift

• Hyperleukocytosis: absolute WBC count >100,000 cells/µL (ie >100.0 cells x 1000/µL) seen in patients with leukemia

Hyperleukocytosis → Clinical Manifestations 🔴

• Leukostasis (↑ Blasts → ↑ Viscosity + Microvascular Occlusion): CNS involvement in ~40% (global encephalopathy 2/2 diffuse ischemia, FND 2/2 focal occlusion, headache 2/2 post-ischemic ICH), pulmonary involvement in ~30% (diffuse parenchymal lung disease → dyspnea +/- hypoxemia), & less frequently GI (microvascular mesenteric ischemia), renal (AKI), cardiac (MINOCA), & other (priapism)

• Tumor Lysis Syndrome: release of large quantities of cellular contents (i.e. K, Phos, nucleic acids) → hyperkalemia (arrhythmias), hyperphosphatemia (hypocalcemic seizures, nephrocalcinosis), hyperuricemia (uric acid nephropathy)

• DIC (↑ Tissue Factor) : ↑ PT/PTT, ↑ d-dimer, ↓ fibrinogen (often false ⊖ 2/2 inflammation)

• Lysis: pseudohyperkalemia

• Consumption: pseudohypoxemia (Normal SpO2 oximetry, ↓ PaO2), pseudohypokalemia, pseudohypoglycemia

Diagnostic Algorithm 🧠

• Step 1 = Smear: blasts (AML > ALL) vs. full myeloid spectrum (CML) vs. full myloid spectrum + blasts (CML in Blast phase) vs. lymphocytes + smudge cells (CLL) vs. neutrophilia with left shift (extreme leukemoid reactions)

• Step 2 = Confirm + Study: flow cytometry (lineage), cytogenetics (translocation)

• Step 3 = Complications: TLS + DIC labs, lung + brain imaging if clinical concerns

Leukostasis, Treatment 👇

• Leukostasis is exceedingly rare in ALL, CML, & CLL, thus the diagnosis should be questioned in these patients with organ dysfunction (e.g. pulmonary infiltrates)

• On the other hand, if the patient has known AML, the decision tree is based on patient’s readiness to undergo intensive induction chemotherapy (e.g. cytarabine + anthracycline) vs. lack of readiness (apharesis + hydryxourea)

• Additionally, CML in Blast phase should be started on TKI, as per usual CML management

⚪ If the patient is presenting for the first time & there is additional concern for associated DIC, all-trans retinoic acid (ATRA) should be given for potential APML prior to the results of “molecular proof” of APML

⚪ Additionally, if the patient is ultimately found to have CML in the Blast phase, the patient will ultimately need a bone marrow transplant for durable survival, because median survival is still < 1 year despite TKIs often stabilizing the patient

Asymptomatic Hyperleukocytosis 👇

• Intensive cytoreduction (AML) vs. hydroxyurea

Hydroxyurea 🌈

• Inhibits ribonucleotide reductase → ↓ DNA synthesis -> ↓ rapid cell proliferation → cytoreduction + bystander effects (myelosuppression → post-treatment cytopenias, mucocutaneous ulcers)

• Major idiosyncratic drug reaction = hepatotoxicity

• Hyperleukocytosis and leukostasis in hematologic malignancies (UpToDate)

• How I treat CML blast crisis (Blood)

• Hyperleukocytosis and Leukostasis (Critical Care Medicine)

• Sudden death due to leukostasis in a subject with undiagnosed chronic lymphocytic leukemia