Leukemoid Reaction or CML? Interpreting Neutrophilia With Toxic Changes
48-year-old woman with 3 days of fever, productive cough, and pleuritic chest pain has WBC 42 × 10^9/L with 90% neutrophils, 6% bands, 2% metamyelocytes, 1% lymphocytes, and 1% monocytes; basophils are 0.5%. Hemoglobin is 12.8 g/dL and platelets 410 × 10^9/L. The smear shows toxic granulation and Döhle bodies but no dysplastic neutrophils. She has no splenomegaly, no weight loss, and no prior abnormal CBC. Her CRP is 180 mg/L and she has a right lower lobe infiltrate. The differential includes a leukemoid reaction and chronic myeloid leukemia. The laboratory is asked to help decide whether marrow or molecular testing is needed urgently.
1. Which morphologic and clinical features favor a leukemoid reaction over CML, and which features would argue against that interpretation?
Read the worked answer
Features favoring a leukemoid reaction include an acute infection, toxic granulation, Döhle bodies, a left shift without prominent basophilia or eosinophilia, a high leukocyte alkaline phosphatase (LAP) score, and absence of splenomegaly. CML classically shows basophilia and eosinophilia, a left shift with a low LAP score, splenomegaly, and constitutional symptoms. However, these features overlap: toxic changes can occur in CML with infection, and basophilia can be subtle. The absence of basophilia does not exclude CML, and a normal platelet count does not settle the diagnosis. The key judgment is that morphology alone cannot reliably distinguish the two; the clinical context makes a reactive process more likely, but CML remains possible if leukocytosis persists or atypical features appear.
2. What test would best confirm CML, and should it be ordered before or after treating the infection?
Read the worked answer
BCR-ABL1 testing by quantitative RT-PCR or FISH is the confirmatory test for CML. In this patient, the strong clinical evidence of infection and absence of basophilia or splenomegaly make immediate testing lower yield. A reasonable approach is to treat the pneumonia and repeat the CBC in 2–4 weeks; leukocytosis should resolve if it is reactive. Order BCR-ABL1 sooner if the WBC does not fall, basophilia or eosinophilia appears, splenomegaly develops, the smear shows dysplastic features, or the patient has unexplained constitutional symptoms. Waiting for infection to resolve avoids false reassurance from a negative test done during a reactive process, but it should not delay testing when CML is genuinely suspected.
3. If BCR-ABL1 is negative, what is the next step in interpretation?
Read the worked answer
A negative BCR-ABL1 result makes CML unlikely but does not explain the leukocytosis by itself. First confirm that the test was adequate and appropriate for the clinical question. Then repeat the CBC after the infection has resolved and review the smear for persistent left shift, dysplasia, or basophilia. If the leukocytosis persists without a reactive cause, consider other myeloid neoplasms, such as atypical CML, chronic neutrophilic leukemia, or a myelodysplastic/myeloproliferative overlap, and obtain hematology consultation and marrow evaluation. In this case, the most likely explanation remains a leukemoid reaction, but the laboratory should communicate that resolution of the infection is the key follow-up test.