Real-world data of MDS and CMML in Japan: results of JALSG clinical observational study-11 (JALSG-CS-11).

We conducted a multicenter, prospective observational study of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML) in Japan. From August 2011 to January 2016, we enrolled 6568 patients. Herein, we report the results for MDS (n = 2747) and CMML (n = 182). The percentage of patients aged 65 years or older was 79.5% for MDS and 79.7% for CMML. The estimated overall survival (OS) rate and cumulative incidence of AML evolution at 5 years were 32.3% (95% confidence interval: 30.2-34.5%) and 25.7% (23.9-27.6%) for MDS, and 15.0% (8.9-22.7%) and 39.4% (31.1-47.6%) for CMML. Both diseases were more common in men. The most common treatment for MDS was azacitidine, which was used in 45.4% of higher-risk and 12.7% of lower-risk MDS patients. The 5-year OS rate after treatment with azacitidine was 12.1% (9.5-15.1%) for of higher-risk MDS patients and 33.9% (25.6-42.4%) for lower-risk patients. The second most common treatment was erythropoiesis-stimulating agents, given to just 20% of lower-risk patients. This is the first paper presenting large-scale, Japanese data on survival and clinical characteristics in patients with MDS and CMML.

Temporal trend in survival for chronic myelomonocytic leukemia in the US: a population-based study.

Outcomes for chronic myelomonocytic leukemia (CMML) are insufficiently characterized at the population level. We analyzed epidemiological trends for patients between 2001 and 2017, focusing on age, sex, race, and long-term survivors. Using the Surveillance, Epidemiology, and End Results Program, we studied 3929 patients, in four time-period (tp) cohorts, based on year of diagnosis [2001-2004 (tp1); 2005-2009 (tp2); 2010-2013 (tp3); 2014-2017 (tp4)]. Stable incidence overall, male predominance, and higher incidence for White versus Black and 'Other' races were noted. Three-year relative survival (RS) increased from 27.9% to 36.9% between tp1 and tp4. The most pronounced increase occurred between tp1 and tp2. All subgroups generally experienced RS improvements over time, except notably Black patients. Improvements for patients aged 85+ (3-year RS 8.4-23.6% between tp1 and tp4) and increases in long-term survivors (5-year OS from 13.2-22.3%) were observed. Additional study is warranted to explore these associations, particularly for Black patients.

Incidence and predisposing factors of infection in patients treated with hypomethylating agents.

OBJECTIVE: Hypomethylating agents may have adverse effects such as cytopenias, cytopenia associated infections and fatality due to infections despite their favorable effects in the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The infection prophylaxis approach is based on expert opinions and real-life experiences. Hence, we aimed to reveal the frequence of infections, predisposing factors of infection and to analyse infection attributable mortality in patients with high-risk MDS, CMML and AML who received hypomethylating agents in our center where routine infection prophylaxis is not applied. MATERIAL-METHOD: 43 adult patients with AML or high-risk MDS or CMML who received HMA ≥ 2 consecutive cycles from January 2014 to December 2020 were enrolled in the study. RESULTS: 43 patients and 173 treatment cycles were analyzed. The median age was 72 years and 61.3 % of patients were males. The distribution of the patients' diagnoses was; AML in 15 patients (34.9 %), high risk MDS in 20 patients (46.5 %), AML with myelodysplasia-related changes in 5 patients (11.6 %) and CMML in 3 patients (7 %). 38 infection events (21.9 %) occurred in 173 treatment cycles. 86.9 % (33 cycles) and 2.6 % (1 cycle) of infected cycles were bacterial and viral infections, respectively and 10.5 % (4 cycles) were bacterial and fungal concurrently. The most common origin of the infection was respiratory system. Hemoglobin count was lower and CRP level was higher at the beginning of the infected cycles significantly (p values were 0.002 and 0.012, respectively). Requirement of red blood cell and platelet transfusions were found to be significantly increased in the infected cycles (p values were 0.000 and 0.001, respectively). While > 4 cycles of treatment and increased platelet count were found to be protective against infection, > 6 points of Charlson Comorbidity Index (CCI) were found to increase the risk of infection. The median survival was 7.8 months in non-infected cycles while 6.83 months in infected cycles. This difference was not statistically significant (p value was 0.077). DISCUSSION: The prevention and management of infections and infection-related deaths in patients treated with HMAs is crucial. Therefore, patients with a lower platelet count or a CCI score of > 6 may be candidates for infection prophylaxis when exposed to HMAs.

Significance of cardiovascular comorbidity in patients with chronic myelomonocytic leukemia.

In a retrospective study, we analyzed the prevalence of common cardiovascular comorbidities in 310 patients with chronic myelomonocytic leukemia (CMML), their potential prognostic impact, and potential correlations with laboratory and molecular features. 115 (36%) patients had a documented cardiovascular comorbidity. In these patients, coronary heart disease 41/115 (36%), atrial fibrillation 34/115 (29%), and hypertension 75/115 (64%) were documented. None of these conditions had a significant impact on survival. Unexpectedly, patients with cardiovascular comorbidity had a lower number of circulating blasts and a lower prevalence of EZH2 mutations. Moreover, time to transformation was significantly longer in these patients. Cardiovascular comorbidity does not seem to have a major impact on prognosis in CMML patients. The unexpected lower transformation rate in these patients needs to be further investigated.

Venous thromboembolism during systemic inflammatory and autoimmune diseases associated with myelodysplastic syndromes, chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasms: a French multicentre retrospective case-control study.

OBJECTIVES: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE. METHODS: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders. RESULTS: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83). CONCLUSIONS: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real-life study.

Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of <50 × 109 /l in a 'real-life' situation. Platelet response occurred in 47 (77%) patients. The median (range) duration of response was 8 (0-69) months. None of the eight still responders who discontinued ELT had relapsed, at a median (range) of 16 (6-23) months after ELT discontinuation. Although 36% of the patients were anti-coagulated or anti-aggregated only 10% of patients had Grade ≥3 bleeding events. Thrombotic events were observed in six (10%) patients, who all but one had a medical history of arterial or venous thrombosis. Progression to acute myeloid leukaemia occurred in four (7%) patients. In this first 'real-life' study, ELT was effective and generally well tolerated in patients with MDS/CMML without excess blasts.

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia.

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age-related groups: <60 years, 60-79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4-year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low-risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML.

Prognostic assessment for chronic myelomonocytic leukemia in the context of the World Health Organization 2016 proposal: a multicenter study of 280 patients.

Knowledge on chronic myelomonocytic leukemia (CMML) patients from Argentina and Brazil is limited. Our series of 280 patients depicted an older age at diagnosis (median 72 years old), 26% of aberrant karyotypes, and a prevalence of myelodysplastic (60%) and CMML-0 subtypes (56%). The median overall survival (OS) was 48.2 months for patients in CMML-0 (Ref.), 24.7 months for those in CMML-1 (HR = 2.0, p = 0.001), and 8.8 months for patients in CMML-2 (HR = 4.6, p < 0.001). In the CMML-0 category, median OS were different between myelodysplastic and myeloproliferative subtypes (63.7 vs 21.2 months, p < 0.001); however, no differences were observed within CMML-1 and CMML-2 subtypes (24.7 vs 23.7 months, p = 0.540, and 9.1 vs 8.2 months, p = 0.160). The prognostic impact of 24 variables and 7 prognostic systems was adjusted to the WHO 2016 after validating their usefulness. Multivariate analysis were performed, and the final model revealed Hb ≥ 8 -< 10g/dL (HR 1.7), Hb < 8g/dL (HR 2.8), poor karyotypes (HR 2.1), WHO 2016-CMML-1 (HR 2.1), and CMML-2 (HR 3.5) as independent adverse clinical parameters in our cohort with a borderline influence of platelets count < 50 × 109/L (HR 1.4). We could validate several scoring systems, the WHO 2016 proposal and its prognostic capability, along with accessible covariates, on predicting the outcome in our series of CMML patients from Latin America.

Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.

The investigational NEDD8-activating enzyme inhibitor pevonedistat is being evaluated in combination with azacitidine versus single-agent azacitidine in patients with higher-risk myelodysplastic syndrome (higher-risk MDS), higher-risk chronic myelomonocytic leukemia (higher-risk CMML), or low-blast acute myeloid leukemia (AML) in a Phase 3 trial PANTHER. To support Asia-inclusive global development, we applied multiregional clinical trial (MRCT) principles of the International Conference on Harmonisation E17 guidelines by evaluating similarity in drug-related and disease-related intrinsic and extrinsic factors. A PubMed literature review (January 2000-November 2019) supported similarity in epidemiology of higher-risk MDS, AML, and CMML in Western and East Asian populations. Furthermore, the treatment of MDS/AML was similar in both East Asian and Western regions, with the same dose of azacitidine being the standard of care. Median overall survival in MDS following azacitidine treatment was generally comparable across regions, and the types and frequencies of molecular alterations in AML and MDS were comparable. Dose-escalation studies established the same maximum tolerated dose of pevonedistat in combination with azacitidine in Western and East Asian populations. Pevonedistat clearance was similar across races. Taken together, conservation of drug-related and disease-related intrinsic and extrinsic factors supported design of an Asia-inclusive Phase 3 trial and a pooled East Asian region. A sample size of ~ 30 East Asian patients (of ~ 450 randomized) was estimated as needed to demonstrate consistency in efficacy relative to the global population. This analysis is presented as an exemplar to illustrate application of clinical pharmacology and translational science principles in designing Asia-inclusive MRCTs. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Azacitidine is the standard of care for myelodysplastic syndromes/low-blast acute myeloid leukemia (AML) across Western and East Asian patients. The first-in-class small-molecule inhibitor of NEDD8-activating enzyme, pevonedistat, has been investigated as a single agent in multiple studies of hematologic and nonhematologic malignancies and in combination with azacitidine in elderly patients with untreated AML. WHAT QUESTION DID THIS STUDY ADDRESS? By applying clinical pharmacology and translational science and International Conference on Harmonisation E17 principles, this study designed an East Asian-inclusive global pivotal Phase 3 trial of pevonedistat, taking into consideration drug-related and disease-related intrinsic and extrinsic factors. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? These analyses provide scientific rationale for Asia-inclusive globalization of the pivotal, Phase 3 PANTHER trial and for pooling clinical data across the East Asian region for assessing consistency in efficacy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? We developed a framework to facilitate efficient global clinical development of investigational therapies for rare cancers and orphan diseases in Asia-inclusive multiregional clinical trials.

Prognostic scoring systems and comorbidities in chronic myelomonocytic leukaemia: a nationwide population-based study.

Outcomes in chronic myelomonocytic leukaemia (CMML) are highly variable and may be affected by comorbidity. Therefore, prognostic models and comorbidity indices are important tools to estimate survival and to guide clinicians in individualising treatment. In this nationwide population-based study, we assess comorbidities and for the first time validate comorbidity indices in CMML. We also compare the prognostic power of: the revised International Prognostic Scoring System (IPSS-R), CMML-specific prognostic scoring system (CPSS), MD Anderson Prognostic Scoring System (MDAPS) and Mayo score. In this cohort of 337 patients with CMML, diagnosed between 2009 and 2015, the median overall survival was 21·3 months. Autoimmune conditions were present in 25% of the patients, with polymyalgia rheumatica and Hashimoto's thyroiditis being most common. Of the tested comorbidity indices: the Charlson Comorbidity Index (CCI), Haematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) and Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI), CCI had the highest C-index (0·62) and was the only comorbidity index independently associated with survival in multivariable analyses. When comparing the prognostic power of the scoring systems, the CPSS had the highest C-index (0·69). In conclusion, using 'real-world' data we found that the CCI and CPSS have the best prognostic power and that autoimmune conditions are overrepresented in CMML.

Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study.

INTRODUCTION: Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) PATIENTS AND METHODS: Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features. RESULTS: Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behçet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1-162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank <0.05). CONCLUSION: This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.

Trends of incidence and survival of patients with chronic myelomonocytic leukemia between 1999 and 2014: A comparison between Swiss and American population-based cancer registries.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic malignancy. Treatment with hypomethylating agents (HMA) was introduced between 2004 and 2006 but its impact on population-based survival remains controversial. The aim of this study was to investigate epidemiological characteristics and survival before and after introduction of HMA treatment. METHODS: We performed a population-based analysis of CMML cases reported to the Cantonal Cancer Registries in Switzerland (SWISS) and the Surveillance, Epidemiology, and End Results (SEER) Program from the United States for 1999-2006 (before HMA) and 2007-2014 (after HMA). Time trends were compared for these two time periods. RESULTS: 423 and 4144 new CMML cases were reported to the SWISS and SEER registries, respectively. We observed an increasing proportion of older patients ≥75 years in the SWISS (50.3%-62.3%) compared to a decreasing one in the SEER population (59.1%-55.1%). Age standardized incidence-rates were similar and remained stable in both countries (0.32-0.38 per 100'000 py). Relative survival (RS) improved significantly in the SEER (3 years 27%-37%; 5 years 19%-23%; p < 0.001 for both) but remained stable in the SWISS population (3 years 48% to 40%; 5 years 34% to 26%; n.s. for both). CONCLUSIONS: With the exception of opposing age-trends, epidemiologic characteristics are similar in both countries and comparable to other population-based registries. RS remains poor and different time trends of population-based survival cannot be faithfully explained by HMA but most likely by changes in diagnostic accuracy within prognostically distinct age-groups.

Autoimmune disorders are common in myelodysplastic syndrome patients and confer an adverse impact on outcomes.

The coexistence of autoimmune disorders (AD) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely recognized, although with distinct results regarding their prevalence and impact on the outcomes of the underlying hematological process. This study was aimed to analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both the presence of clinical symptoms or compatible serological tests. In total, 48% patients were diagnosed as having AD, being hypothyroidism the most commonly reported clinical AD (8%) and antinuclear antibodies the most frequent serological parameter identified (23.2%). The presence of AD was associated with female gender, lower hemoglobin levels, and higher IPSS-R. Overall survival for patients with AD was inferior to those with no AD (69 vs. 88% at 30 months; HR 2.75, P = 0.008). Notably, clinical but not isolated immune serological parameters had an impact on the outcomes of patients with AD. Finally, in a multivariate analysis, the presence of AD (HR 2.26) along with disease risk categories (very low and low vs. intermediate, high, and very high IPSS-R; HR 4.62) retained their independent prognostic value (P < 0.001). In conclusion, AD are prevalent in MDS and CMML patients and have prognostic implications, especially in lower-risk MDS patients.

Blastic Transformation in Mexican Population With Chronic Myelomonocytic Leukemia.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is the most aggressive of chronic leukemias, with short overall survival and a high transformation rate to acute leukemia. We investigated the factors related to blastic transformation in a Mexican population treated at a tertiary referral center. PATIENTS AND METHODS: The records of patients with a diagnosis of CMML from 2000 to 2015 were reviewed. A total of 54 patients were included, with a median age of 71 years and an overall survival of 16 months. The patients with incomplete data were excluded. IBM SPSS Statistics, version 21.0, software was used to perform the statistical analysis. RESULTS: The rate of blastic transformation was 33% (18 patients), and the interval time to progression was 9 months (range, 0-87 months). Comparing the patients who did not undergo blastic transformation to those who did, those with progression to acute leukemia tended to be younger (age, 58 vs. 71 years; P = .001), to have a greater peripheral blood blast count (≥ 2% vs. 0%; P = .003), and were more likely to have immature myeloid precursors circulating in the peripheral blood (94% vs. 64%; P = .02). On multivariate analysis, younger age continued to be a statistically significant factor for progression (hazard ratio, 0.97; 95% confidence interval, 0.929-0.987). CONCLUSION: Mexican patients with CMML that progressed to overt acute leukemia were considerably younger, with a higher tumor burden and short overall survival. In this population, it is important to consider more aggressive treatment at diagnosis, focusing on high-dose chemotherapy and hematopoietic stem cell transplantation within a short period.

Cytogenetics and comorbidity predict outcomes in older myelodysplastic syndrome patients after allogeneic stem cell transplantation using reduced intensity conditioning.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with a curative potential for myelodysplastic syndrome (MDS) patients. Allo-HSCT has substantial risks, particularly in the elderly, and its role for older MDS patients has yet to be defined. METHODS: We analyzed 88 MDS patients aged ≥ 60 years with allo-HSCT after reduced intensity conditioning regimens over the last decade. The study cohort had high risk features; 47 of 88 (53.4%) patients were > 65 years of age, 24 (27%) patients had cytogenetic abnormalities consistent with monosomal karyotype (MKpos), 33 (38%) patients had histological subtype of RAEB-1 and RAEB-2 at diagnosis, and 45 (51%) patients had a hematopoietic cell transplantation-comorbidity index (HCT-CI) of ≥ 3. RESULTS: The 3-year incidence of progression, transplant-related mortality (TRM), and overall survival (OS) were 26% (95% confidence interval [CI], 18%-37%), 35% (95% CI, 26%-47%), and 41% (95% CI, 30%-52%), respectively. MKpos was the only prognostic factor that increased the risk of disease progression compared with good-risk cytogenetics (hazard ratio [HR] = 9.5, P = .003) as well as MKneg (HR = 3.3, P = .01). For TRM, HCT-CI ≥ 3, but not age >65 years, was associated with worse outcomes (HR = 3.1, P = .007). Cytogenetics and HCT-CI enabled us to identify prognostic groups for OS. MKpos patients had the worst 3-year OS (17%), whereas patients with good-risk cytogenetics and HCT-CI < 3 had the best OS (92%). CONCLUSION: Our results confirm that allo-HSCT can provide long-term survival in older MDS patients. Cytogenetics and HCT-CI identify prognostic risk groups and guide selection of older MDS patients who are candidates for allo-HSCT. Cancer 2017;123:2661-70. © 2017 American Cancer Society.

Asthma and risk of myelodysplastic syndromes: a population-based cohort study.

BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS: We undertook this nationwide population-based cohort study on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML). RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis. Seventy-eight patients subsequently developed MDS and nine patients developed CMML during 402 892 person-years. The cumulative risks of developing MDS/CMML among asthma patients were 0.02% (95% CI: 0.01-0.04%) and 0.07% (95% CI: 0.05-0.09%) during the first year and the first five years of follow-up, respectively. The standardised incidence ratio of MDS/CMML among asthma patients overall was 1.6 (95% CI: 1.3-2.0) with little variation across subgroups. CONCLUSIONS: Asthma may be a risk factor for the development of MDS/CMML.

Incidence and survival outcomes of chronic myelomonocytic leukemia in the United States.

Chronic myelomonocytic leukemia (CMML) is an aggressive neoplasm with sparse data on outcomes at a population level. Using Surveillance Epidemiology and End Results (SEER) database, we identified 2238 patients with CMML diagnosed in the period 2003-2013. We found that the disease incidence was significantly higher with advancing age and lower in females, Blacks, and Asian/pacific islanders. Median OS declined significantly with increasing age (age 20-39 - 25 months, age 40-59 - 20 months, age 60-79 - 18 months, and age ≥80 - 11 months, p < .01), but did not vary by gender or race. Median OS has improved in the period 2007-2013 as compared with 2003-2006 (17 months vs. 14 months, p < .01). In spite of advances in CMML biology and therapeutics, in general, the survival of CMML patients remains dismal. More effective therapies are needed to improve the outcomes of CMML.

Chronic inflammation and autoimmunity as risk factors for the development of chronic myelomonocytic leukemia?

In this study, we investigate if chronic inflammation and autoimmunity might be related to the development of chronic myelomonocytic leukemia (CMML). Conducting a case-control study, we included 112 CMML subjects diagnosed at three hematological departments in Denmark between 2003 and 2013. Controls were 231 unmatched chronic lymphatic leukemia (CLL) subjects diagnosed at one of the departments between 2003 and 2012. Subjects with a history of chronic inflammation or autoimmune disorders were retrieved and odds ratios (ORs) calculated. 16.1% of CMML subjects and 6.5% of CLL subjects presented with a history of chronic inflammatory or autoimmune conditions. This was significantly associated with an increased risk of CMML (adjusted OR 3.24, 95% CI: 1.5-7.0). At individual levels, this association was statistically significant for polymyalgia rheumatica and ITP (p values < 0.01 and 0.03, respectively). We found an association of CMML and smoking status (OR 1.42, 95% CI: 1.06-1.90) with more "former smokers" in the CMML group.