Reading Health System, Wyomissing, PA
Ranjan Pathak , Smith Giri , Michael Gary Martin , Vijaya Raj Bhatt
Background: BCR-ABL negative chronic myeloid leukemia (CML) is uncommon without any previous largescale studies. Because of the genetic differences between BCR/ABL negative and positive CML, we compared their characteristics and outcomes in pre and post-imatinib era. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) 18 database and appropriate International Classification of Disease (ICD-O-3) histology codes to identify adult patients with BCR/ABL negative and positive CML diagnosed between 1973 and 2011. Propensity matching was performed using the MatchIt package of R v2.15.2 to create a matched dataset of BCR/ABL negative and positive CML in the pre-imatinib era (cases diagnosed before 2001) and the post-imatinib era (cases diagnosed after 2001).Kaplan Meier survival and multivariate analysis (Cox proportional hazard regression model) were done using SPSS v22.0. Results: 13,374 cases of BCR/ABL positive CML and 82 cases of BCR/ABL negative CML were identified. Patients with BCR/ABL negative CML, compared to BCR/ABL positive CML, were more likely to be older (69 vs. 60 years, p < 0.01) and diagnosed after 2001 (89% vs. 35.3%, p < 0.01). The median OS of BRC/ABL negative and positive CML was 15 months and 47 months respectively. OS was significantly lower among BRC/ABL negative CML (p < 0.01) but only during the post-imatinib era (p < 0.01). Multivariate analysis showed that OS was significantly lower among BRC/ABL negative (HR 2.15; 95% CI 1.57-2.92; p < 0.01) and with older age at diagnosis but better in more recent years. Gender and race did not influence OS. Conclusions: Our study demonstrates that the difference in OS between BRC/ABL positive and negative CML may not be the result of their intrinsic biology behavior, rather due to the powerful impact of tyrosine kinase inhibitors. Preclinical studies have indicated a possible therapeutic role of JAK inhibitors (ruxolitinib) and SRC kinase inhibitors (dasatinib) in select BRC/ABL negative CML. Identification of actionable mutations, development of novel therapies and improvement in transplant techniques have the potential to improve the outcomes of these patients.
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Abstract Disclosures
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