Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms

Abstract

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.

Figure 1

Subclassification of aCML and MDS/MPN by the presence of leukocytosis (≥13 × 10⁹/L), PB myeloid precursors (≥10%), and dysgranulopoiesis (≥10%). Of all 134 patients, 65 (49%) patients fulfilled all 3 criteria for aCML, and the remaining 69 patients were placed under MDS/MPN-U. Of the latter group, 1 patient (arrow) had leukocytosis, no dysgranulopoiesis, and no information on blood myeloid precursors; 5 patients (arrowhead) had neither leukocytosis nor dysgranulopoiesis but did have thrombocytosis.

Figure 2

A case of aCML. (Left) BM biopsy (hematoxylin and eosin, ×500) reveals a hypercellularity (100%) with markedly increased myeloid:erythroid ratio (26:1). Dysplastic megakaryocytes are indicated by arrows; (right) PB smear (Wright Giemsa, ×1000) shows marked leukocytosis with many myeloid precursors (promyelocytes, myelocytes, and metamyelocytes, 23%). Neutrophils show peculiar abnormal nuclear segmentation. (Microscope: Olympus, Tokyo, Japan; camera and software: Q-Capture, Surrey, Canada.)

Figure 3

Survival rates. Compared with MDS/MPN-U, patients with aCML showed a significant inferior OS (12.4 months, 95% CI [9.0-16.1] vs 21.8 months, 95% CI [17.6-28.8]) and ACL-free survival (11.2 months, 95% CI [7.0-13.5] vs 18.9 months, 95% CI [12.3-26.3]).