Characteristics and survival of BCR/ABL negative chronic myeloid leukemia: a retrospective analysis of the Surveillance, Epidemiology and End Results database.

Abstract

BCR/ABL negative or atypical chronic myeloid leukemia (CML) is a rare hematologic malignancy with an estimated incidence of 1–2% of BCR/ABL positive CML. Clinical features of BCR/ABL negative CML resembles those of BCR/ABL positive CML but does not have BCR/ABL fusion gene; rearrangement of platelet-derived growth factor receptor (PDGFR)-A, PDGFR-B or FGFR1 is also absent [Vardiman et al. 2008]. BCR/ABL negative CML, however, is associated with mutations in CSF3R (up to 40%), SETBP1 (~10%) and JAK2V617F (~5%) [Gotlib et al. 2013]. KRAS or NRAS mutations may also be common in BCR/ABL negative CML (35% in a multicenter study) [Wang et al. 2014]. In addition, a study utilizing whole-exome sequencing has revealed the presence of ETNK1 mutations in 8–13% of patients with BCR/ABL negative CML [Gambacorti-Passerini et al. 2015]. World Health Organization (WHO) criteria for the diagnosis of BCR/ABL negative CML additionally include the presence of leukocytosis ⩾13 × 109/l with circulating neutrophil precursors ⩾10%, monocytes <10% and minimal basophils (usually <2%); bone marrow hypercellularity with granulocytic proliferation and dysplasia; and blood and bone marrow blast count of <20% [Vardiman et al. 2008]. The rarity of the disease has largely precluded conduction of any prospective study to optimize treatment strategy of BCR/ABL negative CML. Similarly, the mutations associated with the disease were hitherto undiscovered, which prevented identification of therapeutic targets and drug development. Consequently, BCR/ABL negative CML has been managed with palliative therapy such as hydroxyurea, low-dose cytarabine and interferon, which results in a median overall survival (OS) of approximately 2 years in small retrospective studies [Onida et al. 2002; Breccia et al. 2006]. A recent multicenter study demonstrated that BCR/ABL negative CML is distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms and has a worse OS (12 versus 22 months) and acute myeloid leukemia-free survival (11 versus 19 months) [Wang et al. 2014]. A population-based study on the outcomes of BCR/ABL negative CML is lacking. In this population-based study, we utilized the Surveillance, Epidemiology and End Results (SEER) database to analyze the characteristics and outcomes of BCR/ABL negative CML. Such information is useful for patient education and may provide background information for clinical trials in the future.