Information on cancer prevalence is of major importance for health care planning and resource allocation [41]. For Ph/BCR-ABL-positive CML, European cancer registries such as the Swedish Cancer Registry [26] and the Cancer Registry of Saarland [27], Germany, or SEER [28] from the National Cancer Institute in the USA have not yet provided any prevalence data. There, CML prevalence data are comprised in the common category of “Leukemia.”

Some information on CML prevalence is, however, available from a French epidemiological survey [24, 35]. This retrospective survey had been conducted in northern France with a population of about 4 million inhabitants. For the period of 1985–2006, 906 newly diagnosed Ph/BCR-ABL-positive CML cases could be identified and analyzed. An increasing annual prevalence of 4.1 % during 1998 (prevalence rate (p. r.) of 5.8) to 2002 (p. r. of 6.8) and of 9.3 % during 2003 (p. r. of 7.3) to 2007 (p. r. of 10.4) was observed in this population. The increasing prevalence rate was mainly due to the use of imatinib therapy positively influencing survival and life expectancy of CML patients [35, 42].

Cancer survival depends on the health care system available to the patients [24, 29, 43, 44]. For CML, economic analyses indicated a relationship between effective treatment patterns, quality of life, and health care costs [45–47]. The growing life expectancy with a consequent shift in the age-distribution of the population toward the elderly is an important influencing factor for clinical practices [45, 48]. Thus, cancer outcome appears to be a useful and effective indicator for monitoring a country’s performance in cancer management [44].

In 2006, the European LeukemiaNet (ELN) (http://www.leukemia-net.org) developed recommendations for the medical management of patients of all ages with CML in daily clinical practice [24, 49]. These recommendations were reviewed and updated in 2009 [50–52]. Thus, CML patients should be treated under the guidance of an experienced center with appropriate facilities for cytogenetic and molecular monitoring [49, 53, 54]. Furthermore, the centers should offer and ask patients to be registered in clinical studies [49]. A careful and close monitoring of treatment response and of prognostic factors is required, first to identify development of first-line therapy (imatinib) resistance, intolerance, noncompliance, or progression to advanced-phase disease. Subsequently, the treatment benefits of second-line therapies (dasatinib or nilotinib) or other second-generation tyrosine kinase inhibitors have to be monitored [49–52, 55, 56].

In routine clinical practice, however, a survey of 956 physicians in the USA and in Europe suggests that treatment practices in some areas of CML management are not in line with ELN recommendations [24, 57]. This study using an internet-based questionnaire with 26 multiple choice questions was conducted between November 2005 and January 2006. Problematic areas were optimal timing of treatment decisions under monitoring, and lack of awareness of new molecular monitoring techniques and of the potential benefit of new tyrosine kinase inhibitors [57].

These results were confirmed by two other international studies [24]. First, the “Unmet Needs in Chronic Leukemia” (UNIC) study [58–60] observed therapy response of CML patients after imatinib treatment. This study had been conducted in eight European countries during the period of September 2006 to March 2007 with retrospective chart review of currently treated CML or Ph-positive acute ­lymphatic leukemia patients. Data from 1,551 CML patients could be analyzed. Imatinib resistance occurred in these patients 16 % more often than expected based from results of investigational clinical trials. Only 39 % of all patients received one cytogenetic diagnostic during their imatinib treatment. Further, molecular monitoring recommended by the ELN to be done every 3 months was conducted for every fourth CML patient only. Finally, a mutation analysis in case of imatinib resistance was done only in 43 % of all patients [58].

Second, within the “It’s best to test” study [61],¹ 584 physicians and hematological specialists from 11 European countries were interviewed between November 2007 and February 2008. Knowledge- and practical-based gaps occurred and according to the authors impaired the implementation of the ELN recommendations in the daily management of patients with CML. Although nine of ten physicians in this study claimed to know the ELN guidelines, nearly half of the physicians did not comply with them because of cost, lack of time, and lack of facilities to conduct essential monitoring tests. Some physicians believed that molecular and mutational testing would have no clinical benefit for patients and that cytogenetic and hematological testing would be adequate (see footnote 1) [61].

The increasing patients’ age, as mentioned previously, is also an important factor influencing decisions in daily clinical practice [24]. Although there is in principle equal access to medical care for all patients across Europe [44], the patient’s age seems to be used as a selection criterion for treatment management. An epidemiological survey in the Southeast of Germany [34] observed that only 59 % of the CML patients (median age of 64 years, no inclusion in investigational studies) received imatinib alone, 10.2 % imatinib in combination with hydroxyurea or interferon alpha, 25.8 % hydroxyurea, and 7.6 % interferon alpha. This study had used the database of the Bavarian association of statutory health insurance accredited physicians covering 83.5 % of all outpatients treated in Bavaria with 10.4 million people in 2006 [34].

The use of pre-imatinib era treatment strategies like hydroxyurea, ara-C, or interferon alpha by some physicians as salvage treatment after imatinib failure and unsuitability of SCT still occurs despite the growing availability of newer tyrosine kinase inhibitors [57]. It has been shown that age is no longer a risk factor for worse outcome since the introduction of imatinib as target therapy [62, 63]. With imatinib therapy older age appears to have lost much of its prognostic relevance, suggesting that poor prognosis previously observed with older age was rather related to treatment-associated factors than to the disease biology of CML in older patients [62]. As the long-term outcome is similar to that of younger patients [63], there is no reason to deprive older patients of the treatment with imatinib or newer tyrosine kinase inhibitors [24].

Few data are available on the proportion of patients recruited to clinical trials and on the extent to which the study patients are representative of the whole patient population. A Scottish study [31] indicates that 52 % of CML patients were enrolled in investigational trials, and German studies report an inclusion rate of about 10 % in 1994 [64] and of 64 % between 1998 and 2000 [33]. However, elderly CML patients are underrepresented in investigational clinical trials as a comparison between multicenter trials and population-based registries shows [24]: The median age in multicenter trials [40, 64–79] (Table 2.2B) is reported around 48/49 years, even in studies without age limitation as an inclusion criterion [64, 72, 78], in contrast to a median age between 64 and 67 years in population-based registries [28, 30, 65] (Table 2.2A), concluding that data of clinical studies underestimate the true age of the CML population.

A German survey [33] showed a significant age difference between Ph/BCR-ABL-positive CML patients treated within or outside a clinical study. Patients participating (median age 54.1 years) were on average 10.7 years younger than those who did not participate (median age 64.8 years). The chance for a Ph/BCR-ABL-positive CML patient <65 years to be enrolled in a clinical study was 3.8 times higher than for a CML patient ≥65 years [33].

Furthermore, patient management by a hospital is also a significant positive factor for participation in clinical trials as results from epidemiological observations suggest [24, 33, 43]. CML patients treated in hospitals have a sixfold higher chance to be included in clinical trials than patients treated outside a hospital [33]. Results of a population-based evaluation in the USA indicated a low treatment rate and a substantial mortality among elderly CML patients [45]. Younger CML patients are more likely to be treated in university hospitals or specialized cancer treatment centers [43, 45] where study infrastructure for patient safety and data management are easily available. This patient group has in general a better prognosis and is likely to be a candidate for participation in clinical trials and for bone marrow transplantation [43, 78]. In contrast, elderly patients are mainly taken care of in general hospitals or in specialty practices with a reduced access to investigational therapies [43]. Reasons for noninclusion of elderly patients in trials might also be in some cases immobility and comorbidities of the patients and in others the reluctance of physicians to admit elderly patients [33]. Regarding gender as an influencing factor for participation in clinical trials, relatively more male CML patients are included in clinical trials than females [33], corresponding to the observation that men accept experimental therapies more readily than women [78, 80]. The place of residence (urban or rural) as a demographic factor did not influence participation in clinical studies [24, 33].