Atypical CML Distinct From Related Myelodysplastic/Myeloproliferative Disorders

A rare subtype of disease known as atypical chronic myeloid leukemia (aCML) has been shown to be clinically distinct from a related condition known as unclassifiable myelodysplastic/myeloproliferative neoplasm (MDS/MPN-U). Several clinical and genetic factors seem to differentiate these diseases.

In a 2008 World Health Organization attempt at classifying diseases falling under the MDS/MPN umbrella, aCML was defined by persistent leukocytosis, marked dysgranulopoiesis, and minimal or no monocytosis or basophilia. The presence of BCR-ABL1 or several other genetic rearrangements precludes an aCML diagnosis. For this study, led by Sa A. Wang, MD, of MD Anderson Cancer Center in Houston, researchers analyzed patient archives for 134 patients at 7 large medical centers; results were published in the April 24 issue of Blood.

All patients were confirmed to lack BCR-ABL1. Of the full cohort, 65 cases (49%) fulfilled the three main aCML criteria of persistent leukocytosis, “marked” dysgranulopoiesis (the authors used a ≥ 10% granulocytes cutoff, lacking a specific measure in the WHO guidelines), and greater than 10% myeloid precursors. Those cases were assigned a diagnosis of aCML, while the remaining 69 were diagnosed as MDS/MPN-U.

“Notably, substantial overlapping features between MDS/MPN-U and aCML were observed,” the authors wrote. About 31% of the cohort fulfilled two of the three of those main criteria. Also, though the other WHO criterion of “no basophilia (often ≤ 2% basophils)” was not used for exclusion, the cases that were defined as aCML had a median basophil percentage of 0% and only two patients had greater than 2% basophils.

The researchers found a number of clinical and histological differences between the two groups of patients. Compared with MDS/MPN-U patients, aCML patients had “more frequently increased LDH, organomegaly, worse anemia, thrombocytopenia, higher circulating blasts, and a lower basophil percentage.” The median white blood cell count was significantly higher for aCML patients, at 40.8 × 10⁹ vs 19.4 × 10⁹ (P < .0001).

Treatments given to the two groups were similar. Those with aCML had a median overall survival of 12.4 months and an acute myeloid leukemia (AML)-free survival of 11.2 months; both were significantly worse than with the MDS/MPN-U patients, who had an overall survival of 21.8 months and an AML-free survival of 18.9 months (P = .004 and .003, respectively).

Genotyping showed some differences that did not reach significance, including slightly more mutated RAS with aCML (35% vs 14%), and less JAK2p.V617F (7% vs 19%).

“In summary, we showed that the WHO definition for aCML identifies within the MDS/MPN category a distinct subgroup of patients with a number of adverse clinical features as well as inferior outcomes,” the authors concluded.