Trends in incidence, primary treatment and survival in chronic myelomonocytic leukaemia: a population‐based study of 1359 patients diagnosed in the Netherlands from 1989 to 2012

Chronic myelomonocytic leukaemia (CMML) is a rare, heterogeneous haematological malignancy characterized by features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (Patnaik et al, 2014a). Most (Kantarjian et al, 2006; Fenaux et al, 2009), but not all (Braun et al, 2011), outcome data in CMML come from the few available clinical trials where CMML was grouped with MDS and only included a small number of CMML patients, which were not reported separately. In this regard, population-based studies can provide data complementary to findings from clinical trials by specifically addressing an unselected CMML population. So far, the few available population-based studies in CMML have limitations, including small sample sizes, short study and follow-up length, or registries that only partially cover the country (Osca-Gelis et al, 2012; Visser et al, 2012). Given the paucity of clinical trials and large populationbased studies in CMML, we conducted a large, nationwide population-based study to assess trends in incidence, primary treatment and survival among more than 1300 CMML patients diagnosed in the Netherlands. We selected all CMML patients aged 18 years and older, diagnosed between 1989 and 2012 (n = 1359; median age [range], 75 [22–95] years; 62% males; Table I) with followup until February 2014, from the nationwide populationbased Netherlands Cancer Registry (NCR). The NCR, which is maintained and hosted by the Comprehensive Cancer Centre the Netherlands, has a nationwide coverage of >95% of all malignancies in the Netherlands since 1989. Despite changes in classification, CMML has a separate morphology code in all editions of the International Classification of Diseases for Oncology (ICD-O) and could therefore be identified in the NCR throughout the entire study period (ICD-O1, 9893/3; ICD-O-2, 9868/3 and ICD-O-3, 9945/3). The ICDO classification does not include separate codes for CMML-1 and -2. The NCR ascertains CMML cases that were confirmed by the physician through histology and/or cytology. Data on the dates of birth, diagnosis and last known vital status (alive, death or emigration), sex, hospital of diagnosis and primary treatment (no therapy or only supportive care, chemotherapy and chemotherapy + stem cell transplantation) were available for individual patients. Based on changing classifications and age-adapted treatment approaches, we divided patients into three periods (1989–2000, 2001–2006 and 2007–2012) and four age groups (18–59, 60–69, 70–79 and ≥80 years), unless otherwise stated. Relative survival rates (RSRs) with 95% confidence intervals were calculated according to the classic cohort approach as a measure of disease-specific survival. The RSR is the ratio of the observed survival of patients to the expected survival in the general population for the same age, sex and time-period. The annual age-standardized incidence rate (ASR) of CMML increased until 2007 and thereafter remained stable at around 0 4/100 000 (Fig S1A). The proportion of patients diagnosed aged ≥70 years was 72% (Table I). Seventy-eight percent of the patients were diagnosed in non-university hospitals. Of all patients, 975 (72%), 365 (27%) and 19 (1%) received no therapy or only supportive care, chemotherapy and chemotherapy + stem cell transplantation (CT+SCT) as primary treatment, respectively. The primary treatment was similar during the three periods studied (Fig S2). Chemotherapy was given to 50%, 36%, 25% and 17% of the patients in the four age groups, respectively. CT+SCT was only applied in 13 (11%) of 119 and 6 (2%) of 273 patients aged 18–59 and 60–69 years, respectively (Fig S2). Relative survival (RS) did not improve over time, as 5-year RSRs were 16%, 20% and 20% in the three periods, respectively (Fig 1A). RS was poor among all age groups, reflected in an overall 5-year RSR of 21%, 23%, 20% and 12% for the four age groups, respectively (Fig 1B). Although limited by small numbers (n = 19), the overall 5-year RSR was 29% (95% confidence interval: 10–52%) for patients undergoing CT+SCT as primary treatment. In our large population-based study, the ASR of CMML initially increased, probably as a result of improved case ascertainment, augmented disease awareness and better classification, rather than changes in aetiological factors. The diagnosis of CMML can be challenging as it primarily relies on morphological assessment of blood and bone marrow smears, along with cytogenetic evaluation, in patients with persistent monocytosis. Despite the wellknown diagnostic challenges in CMML, the overall ASR in our cohort is comparable with recent smaller studies from other Western countries (Osca-Gelis et al, 2012; Visser et al, 2012). Our results show that RS was poor in all age groups and did not improve over the past two decades, which indicates the need to improve outcomes for CMML patients. The finding