A Quantitative Assessment of Heterogeneity in Age at Diagnosis among Patients with Chronic Myeloid Leukemia
Open AccessPurpose: Etiological factors for the development of chronic myeloid leukemia (CML) are largely unknown. Previous reports suggest inconsistent relationships between age at diagnosis, race and geography. Given that age at diagnosis is an important risk factor for cancer, we designed a series of descriptive studies to develop a better understanding of the impact that race, socioeconomic status and geography have on the distribution of age at diagnosis and incidence of CML. Clues to etiological factors may be hypothesized from age-specific differences.Methods: Data from 33,985 patients treated with Imatinib as part of the Glivec® International Patient Assistance Program (GIPAP) were described to test for regional variations in age at diagnosis and overall survival (OS). The second study utilized incidence data from the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program for diagnoses of CML between 1977 and 2011 (18,817 cases). Standard descriptive analyses were complemented with age-period-cohort (APC) models adjusting for year of diagnosis and year of birth effects to compare blacks versus whites. The third study compared age at diagnosis and incidence by geographic region and income status using population-based data from the International Agency for Research on Cancer's (IARC) Cancer Incidence in Five Continents (1998-2002). Results: The mean age at diagnosis for GIPAP was 38.5 years (9.4% <20 years and 4.7% >65 years). Asians were youngest (38.3 years). The 3-year OS probability was 89.4% (95% CI, 88.9-89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p<0.0001), time from diagnosis to treatment >1-year (p<0.0001), diagnoses in accelerated or blast crisis (p<0.0001), initial dose of Imatinib >400mg (p<0.0001) and among Latin Americans and Africans (p<0.0001). In the SEER analysis, black males developed CML approximately 9 years earlier than white males with markedly different distribution of age at diagnosis. An interaction between race and age was observed; age-specific incidence rates were higher among blacks diagnosed between the ages of 25 and 49 after which rates were higher for whites. The incidence rate cross-over between blacks and whites was robust to adjustment for calendar period and birth cohort effects (black vs. white female: p=0.0025; black vs. white male: p=0.0042). In the IARC series, a significant interaction (p<0.0001) between age and region exists; no significant differences were seen in age-specific incidence of CML in the <50 age group while significant differences by region exist in the >50 age group. Conclusion: The three descriptive studies achieved the goals of describing the epidemiology of CML in various populations. Differences in age at diagnosis and OS exist within and between regions in low and middle income countries. In the United States, we observed that race is an age-specific effect modifier for CML consistent with etiologic heterogeneity for early- and late-onset CML. International Population based estimates suggest that the median age at diagnosis and incidence varies by region. Results from these three studies provide the foundation for designing analytical studies aimed at addressing biological, geographical and socioeconomic factors for the development of CML.
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Mendizabal_gwu_0075A_12440.pdf | 2018-01-16 | Open Access |
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