The use of interferon-alfa and allogeneic-stem cell transplantation, and more recently of tyrosine-kinase inhibitors (TKIs) has improved the outcome of patients with chronic myeloid leukemia (CML). The purpose of this large scale population-based study is to provide comprehensive, up-to- date analysis of the short- and long-term RS of patients with CML over different treatment eras, with particular focus on the era of TKI targeted therapy.
Data from SEER 9 registries database were selected for the present study. The 9 registries covered about 10% of the US population. A total of 13,871 patients with an initial diagnosis of CML between1975–2009 were reported to the SEER 9 registries. Two patients were excluded from this study because of unknown ages. The remaining 13,869 patients with CML were included for the incidence rate calculations. In 1740 reported cases, CML was not the first primary cancer, 188 cases were diagnosed by autopsy or reported by death certificate, and 52 cases were without active follow-up, leaving 11,888 cases for the survival analysis. Patients were grouped into 3 calendar periods according to year of diagnosis: 1975–1989, 1990–2000, and 2001–2009, representing the three main eras in the history for CML therapy: the era of cytotoxic therapy (busulfan and hydroxyurea), the era of interferon-alfa and allo-SCT; and the TKIs era. Patients were grouped into six age groups. Age-adjusted incidence rate was expressed per 100,000 persons per year. We analyzed relative survival (RS) using the Kaplan-Meier method.
Among 13,869 patients with CML, 7941 were male (57%) with a median age at diagnosis of 66 years (range, 0 to 108 years); 85 % of patients were Caucasians. The incidence of CML was 1.75 cases/100,000 persons per-year, and was essentially stable during the study periods. The incidence increased with age from a rate of 0.09/100,000 among those ≤15 years old to 7.88/100,000 among those ≥75 years old with a relative risk of 85. The male to female ratio was 1.7. There were ethnic and geographic differences in the incidence on CML. The incidence was lowest among American Indian/Alaska Native and Asians/Pacific populations and was highest in Detroit (P<0.05).
Overall, 1-year, 5-year and 10-year RS after diagnosis was 0.74, 0.36 and 0.21, respectively. There were no significant differences in RS between male and female, and Caucasian and African-American patients, but the 10-year RS ratios were considerably higher among Asians compared to Caucasian and African-American patients (P<0.05). The cumulative RS for all patients with CML under study improved significantly with each study period, with the greatest improvement among patients diagnosed during the 2001–2009 period. The 5-year RS ratios were 0.26 for the calendar period 1975–1989, 0.36 for the calendar period 1990–2000, and 0.56 for the calendar period 2001–2009. The cumulative RS were significantly higher in the 2005–2009 calendar period compared with the 2001–2004 calendar period corresponding to the introduction of second generation of TKIs.
As expected, age was a strong predictor of survival through all 3 calendar periods. The 5-year and 10-year RS ratios decreased rapidly for patients age greater than 64 years old. Patients diagnosed in 2001–2009 had the highest RS among all age groups. Of note, the1-year and 5-year RS ratios in all calendar periods were highest in AYA. In the last two calendar periods under study, the 5-year RS ratios improved significantly for all groups (P<.05) except for the group aged <15 years (P>.05). The increases were: from 0.56 to 0.70 for patients aged <15 years, from 0.56 to 0.86 for patients aged 15–29 years, from 0.53 to 0.84 for patients aged 30–49 years, from 0.45 to 0.70 for patients aged 50–64 years, from 0.29 to 0.47 for patients aged 65–74 years and 0.16 to 0.25 for patients aged ≥ 75 years. 1-year and 10-year RS ratios showed similar trends.
The incidence of CML was stable over time; there are ethnic and geographic variations in the incidence of CML. The RS of patients with CML increased with each treatment eras, with the greatest improvement occurring in 2001–2009 for all age groups, presumably because of increasing use of TKIs. Future research should focus on methods to identify and to eliminate residual dormant CML stem cells that cure relapse, so we can achieve the ultimate goal of cure in CML.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.