By Craig E. Litz, M.D.

Chronic myeloid leukemia (CML) is a chronic myeloproliferative disorder characterized by marked neutrophilia with left shift, splenomegaly and the Philadelphia chromosome. Generally, the diagnosis at presentation is morphologically conspicuous on blood smear examination. In 95% of cases, the white blood cell count (WBC) is greater than 100,000/uL (normal: 4,000-10,000/uL) with a prominent left shifted neutrophilia and basophilia. Virtually no other neoplastic or benign hematologic disease shows this pattern.

Occasionally, blood smears from patients with early CML are examined. In these instances, the diagnosis is less clear and knowledge of early blood findings in CML are helpful. Data from the Nagasaki and Hiroshima atomic bomb blast survivors collected by the Atomic Bomb Survivors Health Control Clinic in Japan provide the clearest picture of blood in early CML to date. In their classic 1978 monograph, Kamada and Uchino summarized the blood findings in bomb blast survivors that eventually developed CML. The Clinic had followed all contaminated survivors and their offspring hematologically and, eventually, cytogenetically through the 1950s and 60s. Eventually, 41 patients developed CML. Using WBC in place of time, the authors were able to construct a chronological sequence of findings in CML (Figure).

In CML patients with a mild neutrophilia, basophilia is a universal and early finding. It is so constant in CML that the lack of basophilia virtually excludes the diagnosis. Leukocyte alkaline phosphatase (LAP), an older diagnostic test of historical interest only, decreases very early in the disease course. As the neutrophilia increases past 20,000/uL a neutrophil left shift appears followed later by splenomegaly as the WBC reaches 50,000/uL. Most investigators believe the causative Philadelphia chromosome occurred at time of bomb blast in these survivors. Using this assumption, the time from Philadelphia chromosome to diagnosable disease was estimated at 8 years for CML.

 

Reference
Kamada N, Uchino H Chronologic Sequence in Appearance of Clinical and Laboratory Findings Characteristic of Chronic Myelocytic Leukemia. Blood 51:843-850, 1978.

 

The ProPath Hematopathology Team

Craig E. Litz, M.D., FCAP Director, Hematopathology
Board-certified in Anatomic and Clinical Pathology and Hematopathology by the American Board of Pathology

Dongkun Jack Chang, M.D.
Board-certified in Anatomic and Clinical Pathology and Hematopathology by the American Board of Pathology

Carrie Chenault, M.D., FCAP ProPath Medical Director
Board-certified in Anatomic and Clinical Pathology and Hematopathology by the American Board of Pathology

Crystal Montgomery-Goecker, M.D.
Board-certified in Anatomic and Clinical Pathology and Hematopathology by the American Board of Pathology

John M. Peters, M.D., Ph.D.
Board-certified in Anatomic and Clinical Pathology and Hematopathology by the American Board of Pathology

 

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