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

• Published in: Blood Vol. 123; no. 17; pp. 2645 - 2651
• Main Authors: Wang, Sa A., Hasserjian, Robert P., Fox, Patricia S., Rogers, Heesun J., Geyer, Julia T., Chabot-Richards, Devon, Weinzierl, Elizabeth, Hatem, Joseph, Jaso, Jesse, Kanagal-Shamanna, Rashmi, Stingo, Francesco C., Patel, Keyur P., Mehrotra, Meenakshi, Bueso-Ramos, Carlos, Young, Ken H., Dinardo, Courtney D., Verstovsek, Srdan, Tiu, Ramon V., Bagg, Adam, Hsi, Eric D., Arber, Daniel A., Foucar, Kathryn, Luthra, Raja, Orazi, Attilio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2014; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Blood Platelets - metabolism; Clinical Trials and Observations; DNA Mutational Analysis; Female; Follow-Up Studies; Granulocyte Precursor Cells - metabolism; Hematologic Neoplasms - classification; Hematologic Neoplasms - diagnosis; Hematologic Neoplasms - genetics; Humans; Karyotyping; L-Lactate Dehydrogenase - metabolism; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - diagnosis; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - genetics; Leukocytosis - diagnosis; Male; Middle Aged; Mutation; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - genetics; Myelodysplastic-Myeloproliferative Diseases - diagnosis; Myelodysplastic-Myeloproliferative Diseases - genetics; Prognosis; Proportional Hazards Models; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-02-553800

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. •Within MDS/MPN, the WHO 2008 criteria for aCML identify a subgroup of patients with aggressive clinical features 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.