Marked Leukocytosis With Basophilia and a Low LAP Score
A 55-year-old man reports fatigue and early satiety. The spleen is 6 cm below the costal margin. CBC: WBC 68 ×10^9/L, Hb 10.5 g/dL, platelets 450 ×10^9/L. Differential: neutrophils 60%, bands 8%, metamyelocytes 10%, myelocytes 8%, promyelocytes 2%, basophils 4%, eosinophils 2%, lymphocytes 6%. Leukocyte alkaline phosphatase score is low. He has no fever and no lymphadenopathy. The referring physician asks whether to start hydroxyurea tonight or wait for molecular testing.
1. What is the leading diagnosis, and which test should be ordered first?
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The leading diagnosis is chronic myeloid leukemia (CML) in chronic phase. The combination of marked leukocytosis, left shift, basophilia, splenomegaly, and a low leukocyte alkaline phosphatase score is classic. Order BCR-ABL1 testing by quantitative PCR or FISH on peripheral blood. A bone marrow biopsy is not required to start treatment when the blood findings and BCR-ABL1 are diagnostic. Hydroxyurea can be used for symptomatic hyperleukocytosis or very high counts, but with a WBC of 68 ×10^9/L and no leukostasis, it is reasonable to wait briefly for BCR-ABL1.
2. If BCR-ABL1 is negative, what alternative diagnoses should be considered and what tests help?
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Consider atypical CML, chronic neutrophilic leukemia, chronic myelomonocytic leukemia, leukemoid reaction, and other myeloproliferative neoplasms. Reassess the differential for monocytosis and dysplasia, and review the marrow morphology and cytogenetics. CSF3R mutation testing helps evaluate chronic neutrophilic leukemia. A leukemoid reaction may show toxic granulation, Döhle bodies, and an elevated LAP score, often with infection or tumor. Bone marrow biopsy with karyotype and targeted sequencing is useful when BCR-ABL1 is absent and the picture is not clearly reactive.
3. Once BCR-ABL1 is positive, what monitoring schedule and counseling points matter?
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Start a tyrosine kinase inhibitor such as imatinib or a second-generation agent. Obtain a baseline quantitative BCR-ABL1, then monitor at 3, 6, and 12 months and periodically thereafter. Key milestones include BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, and ≤0.1% at 12 months. Emphasize adherence, drug interactions, and avoidance of pregnancy because TKIs are teratogenic. Rising transcript levels should prompt adherence review and mutation analysis for resistance. The patient should understand that treatment is long-term and that splenomegaly and blood counts usually improve.