REVIEWARTICLE

Epidemiology of chronic myeloid leukaemia: an update

Martin Hglund & Fredrik Sandin & Bengt Simonsson

Received: 18 July 2014 /Accepted: 23 October 2014# Springer-Verlag Berlin Heidelberg 2015

Abstract National and regional population-based registriesare, provided diagnostic accuracy and full coverage of thetarget population, indispensible tools for epidemiological re-search. Chronic myeloid leukaemia (CML) registries withmore comprehensive reporting may also provide complemen-tary data on treatment outcome to those obtained from clinicaltrials. Reports from several European CML registries consis-tently show a crude annual incidence of 0.71.0/100,000, amedian age at diagnosis of 5760 years and a male/femaleratio of 1.21.7. The incidence of CML has been stable overtime. Worldwide, variations in the reported incidence of CMLmay be due to methodological issues, but a true differencebetween different geographical areas and/or ethnical sub-groups cannot be excluded. The prevalence of CML is notwell known but has been estimated to be 1012/100,000 in-habitants with a steady increase due to the dramatic improve-ment in survival of these patients. In recent population-basedstudies, CML patients have an overall survival that is compa-rable to that shown in large clinical trials, though relativesurvival in patients >70 years is still decreased. The impor-tance of socio-economic factors and health-care setting foroutcome and the possible increased risk of secondary cancerin CML are areas of ongoing research.

Keywords Epidemiology . Chronicmyeloid leukaemia(CML) . Incidence . Prevalence . Population-based registries

Population-based registries

Important data on cancer epidemiology (i.e. incidence, mor-tality, age and sex distribution, overall survival) are obtainedfrom cancer registries covering either the entire population ofa nation [1, 2] or selected regions with well-characterised pop-ulations [3]. The National Cancer Registry in Sweden wasformed already in 1958. All pathologists, cytologists and cli-nicians are obliged by law to report each occurrence of cancerthat they diagnose or treat to this centralised, nationwide reg-istry [4]. The Surveillance, Epidemiology, and End Results(SEER) registry collects data on all newly diagnosed cancersfrom US hospitals, including patient demographics form 17tumour registries covering approximately 25 % of the USpopulation [5].

More recently, population-based registries aiming to collectmore detailed data on demographics, baseline patient charac-teristics as well as treatment and outcome in chronic myeloidleukaemia (CML) or other haematological cancers have beeninitiated at the regional or national levels [69]. Examples arethe British Haematological Malignancy Research Network(HMRN), established in 2004 and operating across 14 hospi-tals using a single haematopathology laboratory [3], and thenational Swedish CML Registry, founded in 2002 and cover-ing >95 % of all newly diagnosed cases of CML [8]. At theinternational level, the European Treatment and OutcomeStudy (EUTOS) for CML has collected detailed population-based data on patients with CML diagnosed in 20082012, in27 European countries [10]. Reliability of data from registriesclaiming to be population based presupposes completereporting, diagnostic accuracy, correct coding classificationand a well-characterised background population of the regis-try catchment area(s).

Results from more detailed population-based registrieswith full coverage of the target population are not only usefulsources for epidemiological studies. By reducing the impact of

M. Hglund :B. SimonssonDepartment of Medical Science, Uppsala University Hospital,Uppsala, Sweden

F. SandinRegional Cancer Centre, Uppsala-rebro, Sweden

M. Hglund (*) :B. SimonssonDivision of Hematology (50C), Uppsala University Hospital, 75185 Uppsala, Swedene-mail: martin.hoglund@medsci.uu.se

Ann Hematol (2015) 94(Suppl 2):S241S247DOI 10.1007/s00277-015-2314-2

selection on outcome, they may also provide important com-plementary data on treatment outcome to those obtained fromclinical trials [11]. In addition, further information could beobtained by cross-linking to other population-based databases[12, 13]. Using real-time data from more detailed disease-specific registries may also be helpful in evaluating adherenceto guidelines and in improving the quality of care, includingroutines for diagnostics and follow-up [14]. However, delayedreporting, less stringent monitoring (as compared to clinicaltrials) and no detailed information on treatments are obviouslimitations of population-based registries.

Incidence

Incidence of CML in the total adult population

Published data on the annual incidence of CML varies from aslow as 0.4/100,000 persons in some non-Western countries to1.75/100,000 in the USA [79, 1519]. As the incidence ofCML increases by age, some of these variations are due tosignificant differences in the age distributions of the investi-gated populations (e.g. Western vs several non-Western coun-tries). However, also figures on age-adjusted incidence varyconsiderably (0.71.8/100,000) between different studies(Table 1) [8, 20].

Methodological factors may, at least partly, explain thesediscrepancies. In particular, the inclusion of patients withBCR-ABL-negative myeloproliferative disorders may accountfor the higher incidence of CML in some registries, such asSEER reporting an incidence of 1.75/100,000, varying from1.4 to 2.0 between different regions within the USA [17].Moreover, incorrectly including referral patients in regionalBpopulation-based^ registries leads to an overestimation ofthe incidence. On the other hand, incomplete reporting of

new CML cases will result in too low figures. Several CMLregistries have therefore made considerable efforts to pick upall newly diagnosed cases of CML including those diagnosedat smaller hospitals [8, 9]. Notably, reports from the CMLregistries in UK, Germany and Sweden consistently show anage-adjusted incidence of 0.71.0/100,000 [8, 9, 20, 21].

Although we hypothesise that the divergence in CML in-cidence reported so far is mainly due tomethodological issues,a true difference between different geographical areas and/orethnical subgroups cannot be excluded. Indeed, such differ-ences have been shown in other haematological cancers suchas chronic lymphocytic leukaemia and acute promyelocyticleukaemia [22, 23]. In CML, several reports suggest that theincidence of CML is lower in some Asian countries [16, 24].Thus, Chen et al., analysing the incidence of CML in differentethnical subgroups within the USA, showed a lower incidenceof CML in Asians as compared to Caucasians [17].

Of interest, a recent preliminary report from the EUTOSregistry, based on population-based epidemiological data from2956 patients in 20 countries with cytogenetically confirmedCML diagnosed in 20082012, showed that the raw incidenceof CML varied from 0.76 (UK) to 1.96 (Finland) per 100,000persons [25]. These surprisingly large differences cannot beexplained solely by differences in the age distributions of theparticipating countries and need to be further analysed beforemaking any firm conclusions about possible variations inCML incidence within Europe.

Age and sex differences

The incidence in CML increases by age, at least up to 7580 years (Fig. 1). In Europe, the median age at diagnosis ofCML, as estimated from population-based registries, is 5760 years (Table 1) [9, 20]. Importantly, this is about 10 yearsabove the median age typically seen in clinical trials [19]. In

Table 1 CML incidence of eight different population-based registries or surveys

Registry Time ofobservation

No. ofpatients

Median age Crudeincidence

Age-standardisedincidence

Reference

US (SEERS) 19752009 13,869 66 1.75a Chen et al. [17]

NW France 19852006 906 56 0.8b Corm et al. [29]

Europe (RARECARE project) 19952002 1047 n.d. 1.2 Visser et al. [21]

Taiwan 19972007 2672 n.d. 0.7 Chang et al. [16]

SW Germany 19982000 218 57 0.62 Rohrbacher et al. [19]

Sw. CML registry 20022010 779 60 0.9 Hglund et al. [8]

UK (HMRN) 20042011 242 59 0.97 0.7b Smith et al. [9]

EUTOS 20082012 2956 57 1.0 Hoffman et al. [25]

n.d. no dataa American-standardised populationbWorld-standardised population

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children, CML is a very rare disease with an incidence of 0.61.2 million children/year [26].

CML is more common in males than in females with male-to-female ratio varying between 1.2 and 1.7 in different stud-ies [8, 20, 27]. The gender difference in incidence is lessprominent in younger age groups (Fig. 1).

Has the incidence of CML increased over time?

In several countries, cancer statistics are available since the1970s. Data from SEERS and the Swedish Cancer Registry(Fig. 2) give no clear evidence of a change in incidence ofCML over time [17, 28]. However, changes in the classifica-tion system, as well as the development of more accuratediagnostics by the centralization of haematopathology to more

specialised units and the introduction of cytogenetics, make itvery difficult to compare present figures on incidence withdata from the mid 1980s and earlier.

Prevalence

Reliable data on the exact prevalence of CML are still scarce.Based on results from the Surveillance of Rare Cancer in Eu-rope (RARECARE) project, Visser et al. estimated the preva-lence of CML in 2008 to 5.6/100,000 [21]. In an epidemiolog-ical survey from northern France, Corm et al. reported a prev-alence for 1998, 2003 and 2007, respectively, of 5.8, 6.8 and7.3 per 100,000 inhabitants [29]. Due to the dramatic improve-ment in survival, following the introduction of imatinib andother tyrosine kinase inhibitors, as well as the increasing lifeexpectancy in the general population, one may anticipate thatthe prevalence continues to increase. Thus, based on an excessannual mortality in CML of 1.53, and an annual incidence ofapproximately 1/100,000, Huang et al. estimated that the prev-alence of CML in USA will increase from approximately 70,000 in 2010 (corresponding to a prevalence of approximately11.6/100,000) to reach a near plateau 35 times the annual inci-dence in 2050 (Fig. 3) [30]. Obviously, this trend has profoundpharmaco-economic consequences [31].

Risk factors for developing CML

The aetiology of CML is essentially unknown. Ionising radia-tion is the only established risk factor, having been linked toCML in atomic bomb survivors [32]. Results from a recentpopulation-based case-control study suggested a weak associ-ation between smoking and CML, but this has not yet been

Fig. 1 Annual incidence per100,000 inhabitants in differentage groups of CML patients (n=1039) diagnosed in 20022012(adjusted to the World StandardPopulation, WSP). Data areobtained from the SwedishCancer Registry (www.socialstyrelsen.se/register/halsodataregister/cancerregistret/inenglish)

1970

1975

1980

1985

1990

1995

2000

2005

2010

0

0.5

1

1.5

Age

sta

ndardis

ed* incid

ence p

er 1

00 0

00 inhabitants

Men

Women

* standardised according to the standard world population

Fig. 2 Age-standardised annual incidence (adjusted to WSP) of CMLdiagnosed in 19702010 (n=4393). Data are obtained from the SwedishCancer Registry (www.socialstyrelsen.se/register/halsodataregister/cancerregistret/inenglish). Note that data from 1970s to 1980s may beimprecise due to decentralised haematopathology and no cytogenetics

Ann Hematol (2015) 94(Suppl 2):S241S247 S243

confirmed by other studies [33]. In a study based on the Swed-ish Cancer Registry andMultigenerational Registry, Bjorkholmet al. found no significant familial aggregation of CML [13].

Survival rates and non-disease-related prognostic factors

Overall and relative survival in the population-based setting

Results from a number of population-based studies have con-firmed the dramatic improvement in survival in patients withCML diagnosed since the introduction of tyrosine kinase in-hibitors (TKIs) at the turn of the century [17, 28]. Further-more, studying 832 consecutive patients in CCgR after 2 yearsof treatment with imatinib, Gambacorti-Passerini et al. report-ed that CML-related deaths were uncommon and survival wasnot significantly different from the general population [34].

Previous studies suggest that the survival rate in patientstreated within clinical trials, or in large referral centres, wassignificantly better than that of all patients with CML [35].However, results from at least two large population-basedstudies have shown almost equal figures on survival with thatobtained from the more selected materials, with an estimated5-year overall survival of 85 % for patients diagnosed in achronic phase with no difference between males and females[8, 9]. Relative survival (RS), which might be a more relevantmeasure in an elderly population, was 90 % or higher in pa-tients up to 7580 years. Thus, in countries where TKIs areeasily available, most patients with CML seem to have a lifeexpectancy close to that of the normal population.

Age and co-morbidity

Apart from disease-related pretreatment factors (e.g. stage,Sokal, Hasford and EUTOS score, aberrant cytogenetics),

which are beyond the scope of this overview, several non-disease-related factors might have an impact on the prognosisof CML. A number of studies indicate that, even after theintroduction of imatinib in 20012002, elderly CML patients(>6070 years) have an inferior survival than younger ones[28, 3638], although recent reports fromUK and the GermanCML Study IV concluded that the relative survival was almostidentical for patients under and over 60 (65)years [9, 39].Possibly, the underuse of imatinib (or other TKIs) in the el-derly CML patient populations during the first years after itsintroduction explains the inferior results in the very elderlypopulation as reported in some population-based studies [8].

Do elderly patients respond differently to treatment withTKIs? Previous reports suggest that older patients respondequally well as younger to treatment with imatinib [40], al-though tolerance might be less good [41]. Nevertheless,Proetel et al. showed that older patients (65 years) respondedmore slowly to standard dose imatinib (400 mg/day) thanyounger, but equally well to a higher dose (800 mg/day).Grade 3 and 4 adverse events were similar in both age groups[39]. Clinical implications of these findings are unclear, al-though the authors suggest that the optimal dose of imatinibfor older patients may be higher than 400 mg/day.

In another publication based on patients participating in theGerman CML Study IV, co-morbidity, as measured using theCharlson index [42] and separated from age in the analysis,expectedly was associated with worse survival but had nonegative impact on response to imatinib [43].

Socio-economy and health-care setting

Even in economically more developed countries, socio-economic factors may have an impact on the prognosis inpatients with haematological cancers [15]. In CML, in a recentpopulation-based study from the UK (HMRN), the

Fig. 3 Estimated prevalence ofchronic myeloid leukaemia in theUSA by calendar year, fromHuang et al. [30] (published bythe permission of the authors)

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investigators found that patients living in more deprived areashad poorer outcome in terms of relative survival as well as alower chance to obtain MMR despite treatment with a TKI[9]. Although, the mechanism(s) behind these findings re-mains to be elucidated, the authors speculate that non-adherence to TKI therapy may be the most important factor.Further studies on this subject are warranted.

Previous publications suggested that centralised care ofpatients with CML is important for achieving results compa-rable with those of clinical trials [35, 44]. More recently,Lauseker et al., analysing the outcome of 1491 patients includ-ed in the German CML Study IV, observed a survival advan-tage for patients treated initially at a teaching hospital com-pared to those treated in municipal hospitals and by office-based physicians, respectively [45]. The difference remainedwhen adjusted for age, performance status and EUTOS score.On the other hand, a report from the Swedish CML Registry,based on 779 patients, was not able to find any difference insurvival between patients living in university versus non-university catchment areas [8]. Apart from methodologicalissues, it may well be that the relative importance ofcentralised care in CML differs between countries due to dif-ferences in their health-care resources and organisation.

Do CML patients have an increased risk to develop othercancers?

Studies on the risk of developing subsequent malignancies (oth-er than MDS or acute leukaemia) after the diagnosis of CMLhave yielded somewhat conflicting results. Thus, in a studybased on 1026 patients with CML, diagnosed in 19772008and identified in the Danish Cancer Registry, Fredriksen et al.observed a 1.6-fold increased risk of developing a secondarymalignancy as compared to the expected rate in the backgroundpopulation [46]. In a recent study from the Swedish CML Reg-istry, based on a cohort of 868 patients with CMLCP diagnosedin 20022011, Gunnarsson et al. reported that CML patientshad a 1.5-fold increased risk of developing a secondary canceras compared to the background population (matched by age,sex, health-care region and calendar year at diagnosis) [47].Other investigators, analysing different kinds of study popula-tions, have found that patients with CML have only a slight orborderline increase of secondary cancers [48, 49]. Notably,Verma et al., analysing a large cohort of CML patients treatedbetween 1998 and 2010 at MD Anderson Cancer Center, con-cluded that the number of patients developing invasive malig-nancies were indeed smaller than expected [50]. Differences inpatient numbers, selection, follow-up time and definition ofBsecondary cancer^might explain these contradictory findings.Clearly, the question whether CML patients, nowadays mostlyliving an almost normal lifespan, have an increased risk ofdeveloping other cancers needs to be further investigated.

Acknowledgments The authors appreciate the work of all cliniciansreporting all newly diagnosed cases of CML to the Swedish CMLRegistry.

Conflict of interest Nothing to disclose

References

1. Socialstyrelsen (2009) Cancer incidence in Sweden. www.socialstyrelsense/publikationer1999/1999-42-8

2. StormHH,Michelsen EV, Clemmensen IH, Pihl J (1997) The DanishCancer Registryhistory, content, quality and use. Dan Med Bull44(5):535539

3. Smith A, Roman E, Howell D, Jones R, Patmore R, Jack A,Haemato logica l Mal ignancy Research N (2010) TheHaematological Malignancy Research Network (HMRN): a new in-formation strategy for population based epidemiology and healthservice research. Br J Haematol 148(5):739753. doi:10.1111/j.1365-2141.2009.08010.x

4. Turesson I, Linet MS, Bjorkholm M, Kristinsson SY, Goldin LR,Caporaso NE, Landgren O (2007) Ascertainment and diagnostic ac-curacy for hematopoietic lymphoproliferative malignancies inSweden 1964-2003. Int J Cancer 121(10):22602266. doi:10.1002/ijc.22912

5. http://seer.cancer.gov (2014) SEER. Cancer statistics review 1975-2011.

6. Corm S, Roche L, Micol JB, Coiteux V, Bossard N, Nicolini FE,Iwaz J, Preudhomme C, Roche-Lestienne C, Facon T, Remontet L(2011) Changes in the dynamics of the excess mortality rate in chron-ic phase-chronic myeloid leukemia over 1990-2007: a populationstudy. Blood 118(16):43314337. doi:10.1182/blood-2011-01-330332

7. Harrison SJ, Johnson PR, Holyoake TL (2004) The ScotlandLeukaemia Registry audit of incidence, diagnosis and clinical man-agement of new patients with chronicmyeloid leukaemia in 1999 and2000. Scott Med J 49(3):8790

8. Hglund M, Sandin F, Hellstrom K, Bjoreman M, Bjorkholm M,Brune M, Dreimane A, Ekblom M, Lehmann S, Ljungman P,Malm C, Markevarn B, Myhr-Eriksson K, Ohm L, Olsson-Stromberg U, Sjalander A, Wadenvik H, Simonsson B, Stenke L,Richter J (2013) Tyrosine kinase inhibitor usage, treatment outcome,and prognostic scores in CML: report from the population-basedSwedish CML registry. Blood 122(7):12841292. doi:10.1182/blood-2013-04-495598

9. Smith AG, Painter D, Howell DA, Evans P, Smith G, Patmore R,Jack A, Roman E (2014) Determinants of survival in patients withchronic myeloid leukaemia treated in the new era of oral therapy:findings from a UK population-based patient cohort. BMJ Open4(1):e004266. doi:10.1136/bmjopen-2013-004266

10. Lindoerfer D, Pfirrmann M, Saussele S, Hochhaus A, Engel J,Guilhot J, Rosti G, Mayer J, Indrak K, Castagnetti F, Turkina A,Zaritskey A, Steegmann JL, Hellmann A, Thielen N, Cervantes F,Simonsson B, Colita A, Clark RE, Almeida A, Labar B, Marin D,Ossenkoppele GJ, Bogdanovic A, Dyagil I, Porkka K, OBrien S,Griskevicius L, Panagiotidis P, Thaler J, Zupan I, Lejniece S, EverausH, Masszi T, Melanthiou F, Hehlmann R, Hasford J, Baccarani M(2013) CML patients in clinical trials represent fairly well the generalpopulation of CML patients: a comparative analysis of 5803 patientsfrom the EUTOS Registry, vol 122. vol 21

11. Juliusson G, Lazarevic V, Horstedt AS, Hagberg O, Hoglund M(2012) Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 119(17):38903899. doi:10.1182/blood-2011-12-379008

Ann Hematol (2015) 94(Suppl 2):S241S247 S245

12. Berglund A, Holmberg L, Tishelman C, Wagenius G, Eaker S,Lambe M (2010) Social inequalities in non-small cell lung cancermanagement and survival: a population-based study in centralSweden. Thorax 65(4):327333. doi:10.1136/thx.2009.125914

13. Bjorkholm M, Kristinsson SY, Landgren O, Goldin LR (2013) Nofamilial aggregation in chronic myeloid leukemia. Blood 122(3):460461. doi:10.1182/blood-2013-05-501312

14. Carlhed R, Bojestig M,Wallentin L, LindstromG, Peterson A, AbergC, Lindahl B (2006) Improved adherence to Swedish national guide-lines for acute myocardial infarction: the Quality Improvement inCoronary Care (QUICC) study. Am Heart J 152(6):11751181. doi:10.1016/j.ahj.2006.07.028

15. Bhayat F, Das-Gupta E, Smith C, McKeever T, Hubbard R (2009)The incidence of and mortality from leukaemias in the UK: a generalpopulation-based study. BMC Cancer 9:252. doi:10.1186/1471-2407-9-252

16. Chang CS, Lee K, Yang YH, Lin MT, Hsu CN (2011) Estimation ofCML incidence: disagreement between national cancer registry andhealth claims data system in Taiwan. Leuk Res 35(5):e53e54. doi:10.1016/j.leukres.2010.12.034

17. Chen Y, Wang H, Kantarjian H, Cortes J (2013) Trends in chronicmyeloid leukemia incidence and survival in the United States from1975 to 2009. Leuk Lymphoma 54(7):14111417. doi:10.3109/10428194.2012.745525

18. Hasford J, Tauscher M, Hochhaus A (2007) Incidence, comorbidityand treatment survey of chronic myeloid leukemia in Germany. ASHAnn Meet Abstr 110(11):2964

19. Rohrbacher M, Berger U, Hochhaus A, Metzgeroth G, Adam K,Lahaye T, Saussele S, Muller MC, Hasford J, Heimpel H,Hehlmann R (2009) Clinical trials underestimate the age of chronicmyeloid leukemia (CML) patients. Incidence and median age of Ph/BCR-ABL-positive CML and other chronic myeloproliferative dis-orders in a representative area in Germany. Leukemia 23(3):602604.doi:10.1038/leu.2008.245

20. Rohrbacher M, Hasford J (2009) Epidemiology of chronic myeloidleukaemia (CML). Best Pract Res Clin Haematol 22(3):295302.doi:10.1016/j.beha.2009.07.007

21. Visser O, Trama A, Maynadie M, Stiller C, Marcos-Gragera R, DeAngelis R, Mallone S, Tereanu C, Allemani C, Ricardi U, SchoutenHC, GroupRW (2012) Incidence, survival and prevalence ofmyeloidmalignancies in Europe. Eur J Cancer 48(17):32573266. doi:10.1016/j.ejca.2012.05.024

22. Gale RP, Cozen W, Goodman MT, Wang FF, Bernstein L (2000)Decreased chronic lymphocytic leukemia incidence in Asians inLos Angeles County. Leuk Res 24(8):665669

23. Matasar MJ, Ritchie EK, Consedine N, Magai C, Neugut AI (2006)Incidence rates of acute promyelocytic leukemia among Hispanics,blacks, Asians, and non-Hispanic whites in the United States. Eur JCancer Prev 15(4):367370

24. Kim DW, Banavali SD, Bunworasate U, Goh YT, Ganly P, Huang H,Irving I, Jootar S, Goh HG, Koh LP, Li W, Naoe T, Ng SC,Purushotaman V, Reksodiputro H, Shih LY, Tang JL, Tojo A, WangJ, Wong R (2010) Chronic myeloid leukemia in the Asia-Pacificregion: current practice, challenges and opportunities in the targetedtherapy era. Leuk Res 34(11):14591471. doi:10.1016/j.leukres.2010.03.033

25. HoffmannV, Lindoerfer D, Thaler J, Labar B,Melanthiou F,Mayer J,Everaus H, Porkka K, Guilhot F, Schubert-Fritschle G, Castagnetti F,Lejniece S, Griskevicius L, Thielen N, Hellmann A, Turkina A,Zaritskey A, Bogdanovic A, Indrak K, Zupan I, Casado L-F,Simonsson B, Clark RE, Hehlmann R, Hasford J, Baccarani M(2014) The EUTOS population based registryincidences of CMLacross Europe. European Hematology Association Annual Meeting2014

26. de la Fuente J, Baruchel A, Biondi A, de Bont E, Dresse MF, SuttorpM, Millot F, International BFMGSGCMLC (2014) Managing

children with chronic myeloid leukaemia (CML): recommendationsfor the management of CML in children and young people up to theage of 18 years. Br J Haematol 167(1):3347. doi:10.1111/bjh.12977

27. Berger U, Maywald O, Pfirrmann M, Lahaye T, Hochhaus A, ReiterA, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, Loffler H, Pralle H,Queisser W, Hehlmann R (2005) Gender aspects in chronic myeloidleukemia: long-term results from randomized studies. Leukemia19(6):984989. doi:10.1038/sj.leu.2403756

28. BjorkholmM, OhmL, Eloranta S, Derolf A, HultcrantzM, Sjoberg J,Andersson T, Hoglund M, Richter J, Landgren O, Kristinsson SY,Dickman PW (2011) Success story of targeted therapy in chronicmyeloid leukemia: a population-based study of patients diagnosedin Sweden from 1973 to 2008. J Clin Oncol 29(18):25142520.doi:10.1200/JCO.2011.34.7146

29. Corm S, Micol JB, Leroyer A, Daudignon A, Preudhomme C,Poulain B, Bregman B, Oukessou A, Lai J, Facon T (2008) Kineticof chronic myeloid leukemia (CML) prevalence in Northern Francesince the introduction of imatinib. J Clin Oncol (Suppl) 26(15S):7088

30. Huang X, Cortes J, Kantarjian H (2012) Estimations of the increasingprevalence and plateau prevalence of chronic myeloid leukemia inthe era of tyrosine kinase inhibitor therapy. Cancer 118(12):31233127. doi:10.1002/cncr.26679

31. Ohm L, Lundqvist A, Dickman P, Hoglund M, Persson U, Stenke L,Steen Carlsson K, Bjorkholm M (2014) Real-world cost-effective-ness in chronic myeloid leukaemia: the price of success during fourdecades of development from non-targeted treatment to imatinib.Leuk Lymphoma 116. doi:10.3109/10428194.2014.953141

32. Heyssel R, Brill AB, Woodbury LA, Nishimura ET, Ghose T,Hoshino T, Yamasaki M (1960) Leukemia in Hiroshima atomicbomb survivors. Blood 15:313331

33. Musselman JR, Blair CK, Cerhan JR, Nguyen P, Hirsch B, Ross JA(2013) Risk of adult acute and chronic myeloid leukemia with ciga-rette smoking and cessation. Cancer Epidemiol 37(4):410416. doi:10.1016/j.canep.2013.03.012

34. Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, DeiningerM, Fava C, Nagler A, Della Casa CM, Morra E, Abruzzese E,DEmilio A, Stagno F, le Coutre P, Hurtado-Monroy R, Santini V,Martino B, Pane F, Piccin A, Giraldo P, Assouline S, DurosinmiMA, Leeksma O, Pogliani EM, Puttini M, Jang E, Reiffers J,Valsecchi MG, Kim DW (2011) Multicenter independent assessmentof outcomes in chronic myeloid leukemia patients treated with imatin-ib. J Natl Cancer Inst 103(7):553561. doi:10.1093/jnci/djr060

35. Pulte D, Gondos A, Redaniel MT, Brenner H (2011) Survival ofpatients with chronic myelocytic leukemia: comparisons of estimatesfrom clinical trial settings and population-based cancer registries.Oncologist 16(5):663671. doi:10.1634/theoncologist. 2010-0393

36. Brunner AM, Campigotto F, Sadrzadeh H, Drapkin BJ, Chen YB,Neuberg DS, Fathi AT (2013) Trends in all-cause mortality amongpatients with chronic myeloid leukemia: a Surveillance,Epidemiology, and End Results database analysis. Cancer 119(14):26202629. doi:10.1002/cncr.28106

37. Shah BK, Ghimire KB (2013) Chronic myeloid leukemia survival inolder population in the United States. Leuk Lymphoma. doi:10.3109/10428194.2013.775435

38. Wiggins CL, Harlan LC, Nelson HE, Stevens JL,Willman CL, LibbyEN, Hromas RA (2010) Age disparity in the dissemination of ima-tinib for treating chronic myeloid leukemia. Am J Med 123(8):764e761-769. doi:10.1016/j.amjmed.2010.03.018

39. Proetel U, Pletsch N, Lauseker M, Muller MC, Hanfstein B, KrauseSW, Kalmanti L, Schreiber A, Heim D, Baerlocher GM, HofmannWK, Lange E, Einsele H, Wernli M, Kremers S, Schlag R, Muller L,Hanel M, Link H, Hertenstein B, Pfirrman M, Hochhaus A, HasfordJ, Hehlmann R, Saussele S, German Chronic Myeloid LeukemiaStudy G, Schweizerische Arbeitsgemeinschaft fur Klinische K(2014) Older patients with chronic myeloid leukemia (65 years)profit more from higher imatinib doses than younger patients: a

S246 Ann Hematol (2015) 94(Suppl 2):S241S247

subanalysis of the randomized CML-Study IV. Ann Hematol 93(7):11671176. doi:10.1007/s00277-014-2041-0

40. Gugliotta G, Castagnetti F, Palandri F, Breccia M, Intermesoli T,Capucci A, Martino B, Pregno P, Rupoli S, Ferrero D, GherlinzoniF, Montefusco E, Bocchia M, Tiribelli M, Pierri I, Grifoni F,Marzocchi G, Amabile M, Testoni N, Martinelli G, Alimena G,Pane F, Saglio G, Baccarani M, Rosti G (2011) Frontline imatinibtreatment of chronic myeloid leukemia: no impact of age on outcome,a survey by the GIMEMA CML Working Party. Blood 117(21):55915599. doi:10.1182/blood-2010-12-324228

41. Breccia M, Alimena G (2013) The role of comorbidities in chronicmyeloid leukemia. Leuk Res 37(7):729730. doi:10.1016/j.leukres.2013.04.001

42. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A newmethod of classifying prognostic comorbidity in longitudinal studies:development and validation. J Chron Dis 40(5):373383

43. Krauss MP, Lauseker M, Hehlmann R, Proetel U, Schreiber A,Kalmanti L, Hanfstein B, Einsele H, Falge C, Kanz L, Neubauer A,Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, BaerlocherGM, Heim D, Krause SW, Hofmann WK, Hasford J, Hochhaus A,Pfirrmann M, Mller MC (2013) Comorbidity, measured by theCharlson index, has no negative impact on remission in patients withchronic myeloid leukemia: results of the randomized CML-Study IV,vol 122. vol 21.

44. Faber E, Muzik J, Koza V, Demeckova E, Voglova J, DemitrovicovaL, Chudej J, Markuljak I, Cmunt E, Kozak T, Tothova E, JarosovaM,Dusek L, Indrak K (2011) Treatment of consecutive patients withchronic myeloid leukaemia in the cooperating centres from theCzech Republic and the whole of Slovakia after 2000a report fromthe population-based CAMELIA Registry. Eur J Haematol 87(2):157168. doi:10.1111/j.1600-0609.2011.01637.x

45. Lauseker M, Hasford J, Pfirrmann M, Hehlmann R, GermanCMLSG (2014) The impact of health care settings on survival timeof patients with chronic myeloid leukemia. Blood 123(16):24942496. doi:10.1182/blood-2013-11-539742

46. Frederiksen H, Farkas DK, Christiansen CF, Hasselbalch HC,Sorensen HT (2011) Chronic myeloproliferative neoplasmsand subsequent cancer risk: a Danish population-based cohortstudy. Blood 118(25):65156520. doi:10.1182/blood-2011-04-348755

47. Gunnarsson N, Stenke L, Hglund M, Sandin F, Bjrkholm M,Dreimane A, Lambe M, Markevrn B, Olsson-Strmberg U, RicherJ, Wadenvik H, Wallvik J, Sjlander A (2014) Second malignanciesfollowing treatment of chronic myeloid leukemia in the tyrosine ki-nase inhibitor era. ASH Annual Meeting Abstracts 2014, abstract no154. Br. J. Haematol. doi:10.1111/bjh.13346

48. Rebora P, Czene K, Antolini L, Gambacorti Passerini C, Reilly M,Valsecchi MG (2010) Are chronic myeloid leukemia patients more atrisk for second malignancies? A population-based study. Am JEpidemiol 172(9):10281033. doi:10.1093/aje/kwq262

49. Voglova J, Muzik J, Faber E, Zackova D, Klamova H, Steinerova K,Michalovicova Z, Demitrovicova L, Cmunt E, Novakova L, TothovaE, Belohlavkova P, Mayer J, Indrak K (2011) Incidence of secondmalignancies during treatment of chronic myeloid leukemia withtyrosine kinase inhibitors in the Czech Republic and Slovakia.Neoplasma 58(3):256262

50. Verma D, Kantarjian H, Strom SS, Rios MB, Jabbour E, Quintas-Cardama A, Verstovsek S, Ravandi F, OBrien S, Cortes J (2011)Malignancies occurring during therapy with tyrosine kinase inhibi-tors (TKIs) for chronic myeloid leukemia (CML) and other hemato-logic malignancies. Blood 118(16):43534358. doi:10.1182/blood-2011-06-362889

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Epidemiology of chronic myeloid leukaemia: an updateAbstractPopulation-based registriesIncidenceIncidence of CML in the total adult populationAge and sex differencesHas the incidence of CML increased over time?

PrevalenceRisk factors for developing CMLSurvival rates and non-disease-related prognostic factorsOverall and relative survival in the population-based settingAge and co-morbiditySocio-economy and health-care setting

Do CML patients have an increased risk to develop other cancers?References