Trends in Chronic Myeloid Leukemia Survival in the United States From 1975–2009

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3780-3780
Author(s):  
Yiming Chen ◽  
Haijun Wang ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian

Abstract Abstract 3780 Background: 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. Patients and methods: 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. Results: 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. Conclusions: 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. Disclosures: No relevant conflicts of interest to declare.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17005-e17005
Author(s):  
Rakesh Mandal ◽  
Binay Kumar Shah

e17005 Background: Information on trend of Chronic Myeloid Leukemia (CML) incidence rate is scant. This study was conducted to evaluate the time trends of CML incidence rates among Caucasians in the U.S. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to extract annual age-adjusted incidence rates of CML from 1973-2008 for <60yr and >60yr age groups classified by gender. Trends of incidence rates were evaluated using the National Cancer Institute’s Joinpoint Regression Program (v 3.5.2). The maximum number of joinpoints used was 4. The annual percentage change (APC %) for the final selected joinpoint model for each cohort is shown in the table. Results: The annual age-adjusted CML incidence rates for 1973 vs. 2008 were 0.72/0.67, 5.67/4.47, 0.93/0.67, and 10.5/8.5 per 100,000 population for the 4 cohorts: women (<60yr, >60yr) and men (<60yr, >60yr), respectively. Among Caucasian women (>60yr), the incidence rate decreased significantly from 5.58/100,000 in 2001 to 4.47/100,000 in 2008 (APC= -3.08, CI -5.8 to -0.3, p = 0.004). The incidence trend from 1973-2001 was stable for this cohort (APC=0.1, CI -0.3 to 0.5). The incidence trends among women <60yr, men <60yr, and men >60yr were stable from 1973-2008. Conclusions: The annual age-adjusted incidence rates of chronic myeloid leukemia among older (>60 year) Caucasian women has declined sharply from 2001-2008. The rate change is unexplained. It may help generate hypotheses regarding risk factors for CML. [Table: see text]


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4798-4798 ◽  
Author(s):  
Selim Corm ◽  
Ariane Leroyer ◽  
Mathieu Wemeau ◽  
Bruno Bregman ◽  
Abderrahim Oukessou ◽  
...  

Abstract Purpose: To assess the incidence of chronic myeloid leukemia (CML) in the Nord-Pas de Calais Region in Northern France (~ 4 millions inhabitants) and to describe the patients (pts) characteristics and evolution. Methods: A retrospective study was conducted to record all confirmed diagnosis of CML that occurred during the period 1985–2004. All pts were actually living in the region at the diagnosis. CML was diagnosed by cytogenetic and molecular tests (Philadelphia chromosome and/or BCR-ABL fusion gene). Pts were screened through the results of the two cytogenetic and molecular laboratories of the region. The possibility of pts diagnosed outside the region is negligible and under study. Age-standardized incidence rate calculation was based on the standard world population. Results: 783 pts with confirmed diagnosis of CML were included. Age-standardized incidence rate is 0.82/100,000 people during the 1990–2004 period, with a raw incidence rate of 1.02/100,000 people during the same period. In the whole 20 years cohort, 55.7% of the pts are of male gender and the median age at diagnosis is 55.3 years (5.4–93.4). Haematological status at diagnosis was available for 83.5% of pts: chronic phase (CP) for 623 pts (95.3%), accelerated phase (AP) for 21 pts (3.2%), and blastic crisis (BC) for 10 pts (1.5%). Sokal index was available for 67% of pts, and was low for 40.5%, intermediate for 35.9%, and high for 23.6% of them. At December 31th 2004, 331 (42.3%) pts were still alive, 370 (47.2%) were deceased and 82 (10.5%) of unknown status. Taking into account the patients who have left the region, the raw prevalence rate is 8.1/100,000 people at this date. During the follow-up, an advanced phase was documented for 206 pts (26.5%) of the whole cohort and 189 (48.5%) of deceased patients. Allogeneic bone marrow transplantation was performed in 140 (17.9%) pts with a 5-years overall survival rate of 60%. 354 pts (45.2%) received interferon alfa (IFN) (median treatment duration 13.5 Mo (0.5–157.1)) with 24.6% pts achieving a major cytogenetic response (MCyR). 302 pts (38.6%) were treated by imatinib mesylate (IM) (median treatment duration 31.3 Mo (0.5–72.3)) with a rate of MCyR of 75.2% for pts in CP at IM initiation (206 informative pts). The overall median survival of the whole cohort was 72 months. For the diagnosis periods 1985–1989, 1990–1994, 1995–1999, and 2000–2004, the 5-years overall survival rates were respectively 41.6%, 51%, 57.5%, and 78.5% (p&lt;0.0001). Conclusion: our findings in a well defined region corroborate the results of other cancer registries for the CML incidence. The prognosis of this disease has been modified by bone marrow transplantation and the use of interferon alfa but the major survival improvement seems related to the large use of tyrosine kinase inhibitors since 2000–2001, suggesting a great increase of CML prevalence in the future. Overall Survival According to year diagnosis Overall Survival According to year diagnosis


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4432-4432
Author(s):  
Kudrat Abdulkadyrov ◽  
Elza Lomaia ◽  
Natalia Lazorko ◽  
Vasiliy Shuvaev ◽  
Alla Abdulkadyrova ◽  
...  

Abstract Abstract 4432 Background: The incidence of chronic myeloid leukemia (CML), reported from some population based registries, varies significantly. CML is known as age-dependent disease, so population age structure may strongly influent on the data. For international comparisons several systems for age-standardization are using in epidemiological studies. We conducted our retrospective study to reveal differences in CML incidence rates on the basis of calculation – crude or age-adjusted according to different population standards in St. Petersburg and Leningrad region. Methods: In 2005 the database of Ph- and/or bcr-abl- positive CML patients (pts) was conducted in St. Petersburg and Leningrad region. Since then the data from all newly diagnosed CML patients were included prospectively on population basis. The database was updated at least bi-annually. The data were obtained from hematologists, as general practitioners and private physicians are not licensed to treat oncohematological disorders. The data were double checked from the list of Imatinib distribution (the only drug reimbursed for first line treatment). To calculate crude CML incidence rate we use the data of the general census of the population in Russia in 2010 (the whole population of our region is 6596434 with population in age 15 and above 5821133). For age-adjusted CML incidence rate we use three of currently existing standards: The Segi (“World”), The Scandinavian (“European”) and the WHO standard (based on world average population between 2000–2025). Results: There are 258 (242 in chronic, 9 in accelerated and 7 in blastic phases) CML adult (15 years and above) pts, registered during 2006–2011. The median age is 53 years (48,5 and 55,5 years for men and women respectively). Sokal score was evaluable in 209 pts. It is low in 37%, intermediate in 35% and high in 28% pts. The crude CML incidence rate is slightly higher in men than in women with ratio 1,2:1. Mean annual crude CML incidence rate was 0,65 per 100 000 whole population of Saint Petersburg and Leningrad region, but it was 0,74 in adult population (15 years old and above). Mean annual CML incidence rates in the same age groups were slightly higher in all three standardized systems: 0,94 in Segi, 0,84 in Scandinavian and 0,88 in WHO standard populations. CML incidence rates in all age groups are presented in the table 1. CML incidence rate was lowest in young pts. It was unexpectedly very low in senior pts. CML incidence rates nearly for all age groups were slightly higher in St. Petersburg than in the Leningrad region. The majority of pts (98%) were treated with Imatinib (93% first or second line) or other tyrosine kinase inhibitors (5% first line-in international clinical trials, 18% after Imatinib failure or intolerance). Stem cell transplantation was performed only in 8/258 (3%) pts. Only 25235 (7,5%) evaluable pts progressed from chronic to advanced phases. Only 29/258 (11%) pts dead mostly due to CML (21 CML related deaths were reported). Estimated 5 years overall survival is 91,5%. Mean annual overall CML pts death rate was 1,9% (mean annual death rate between 2006–2010 in whole population of our region was 1,6%). Mean pts accumulated very fast - annual CML prevalence increasing rate between 2005–2011 was more than 14% (Picture 1). Conclusions: CML incidence both crude and age-adjusted in our population based registry is nearly the same in young and middle age, but much lower in senior (65 years and above) pts groups in comparison with published data from other registries which probably represents peculiarities of health system rather than real incidence. In the tyrosine kinase inhibitors era CML patients death rate is very low (nearly the same as in whole population) and CML pts is accumulated very fast in our region. Disclosures: No relevant conflicts of interest to declare.


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Andreas Hochhaus

Abstract Elucidation of the pathogenesis of chronic myeloid leukemia (CML) and the introduction of tyrosine kinase inhibitors (TKIs) has transformed this disease from being invariably fatal to being the type of leukemia with the best prognosis. Median survival associated with CML is estimated at > 20 years. Nevertheless, blast crisis occurs at an incidence of 1%-2% per year, and once this has occurred, treatment options are limited and survival is short. Due to the overall therapeutic success, the prevalence of CML is gradually increasing. The optimal management of this disease includes access to modern therapies and standardized surveillance methods for all patients, which will certainly create challenges. Furthermore, all available TKIs show mild but frequent side effects that may require symptomatic therapy. Adherence to therapy is the key prerequisite for efficacy of the drugs and for long-term success. Comprehensive information on the nature of the disease and the need for the continuous treatment using the appropriate dosages and timely information on efficacy data are key factors for optimal compliance. Standardized laboratory methods are required to provide optimal surveillance according to current recommendations. CML occurs in all age groups. Despite a median age of 55-60 years, particular challenges are the management of the disease in children, young women with the wish to get pregnant, and older patients. The main challenges in the long-term management of CML patients are discussed in this review.


2014 ◽  
Vol 61 (10) ◽  
pp. 1774-1778 ◽  
Author(s):  
Karim Thomas Sadak ◽  
Kara Fultz ◽  
Adam Mendizabal ◽  
Gregory Reaman ◽  
Pat Garcia-Gonzalez ◽  
...  

2003 ◽  
Vol 21 (8) ◽  
pp. 1472-1479 ◽  
Author(s):  
Jose Roman-Gomez ◽  
Juan A. Castillejo ◽  
Antonio Jimenez ◽  
Francisco Cervantes ◽  
Concepcion Boque ◽  
...  

Purpose: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene. Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease. Patients and Methods: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR. Results: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P < .0001). Advanced-stage samples (n = 52) showed concordant methylation results with their corresponding CP tumors, indicating that CDH13 methylation was not acquired during the course of the disease. Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P = .01) and was also independently associated with a shorter median progression-free survival time (P = .03) and poor cytogenetic response to interferon alfa treatment (P = .0001). Conclusion: Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.


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