While chronic myeloid leukemia may affect thousands each year, the death rate has plummeted by two-thirds since 2000, making it one of modern medicine's most profound success stories.
Key Takeaways
- The age-standardized incidence rate of chronic myeloid leukemia (CML) in the United States for 2017-2021 was 2.0 per 100,000 persons per year
- Globally, CML accounts for approximately 15% of all leukemias in adults, with an estimated 35,000 new cases worldwide in 2020
- In Europe, the annual incidence of CML is 1.0-1.5 cases per 100,000 population, varying by country with higher rates in Northern Europe
- CML is diagnosed more frequently in males (1.6:1 male:female ratio globally)
- Median age at CML diagnosis in Europe is 59 years, with 60% over 55
- In US, 11% of CML patients are under 45 years old at diagnosis
- Imatinib first-line therapy achieves major cytogenetic response (MCyR) in 82% of chronic phase CML patients at 12 months
- Dasatinib 100mg daily yields complete cytogenetic response (CCyR) in 91% of newly diagnosed CML-CP patients by 12 months
- Nilotinib 300mg BID achieves MMR in 73% of CML-CP patients at 24 months in ENESTnd trial
- Overall survival with TKIs in CP-CML >90% at 10 years
- 10-year OS for imatinib-treated CML-CP: 83.3% (IRIS trial update)
- CML-CP landmark OS at 8 years: 94% for optimal responders, 89% suboptimal
- Philadelphia chromosome BCR-ABL1 detected in 95% of CML cases
- BCR-ABL1 p210 transcript in 99% adult CML, rare variants e1a2 1-2%
- Additional cytogenetic abnormalities (ACA) at diagnosis in 5-10% CP-CML
CML rates are stable worldwide and survival rates have dramatically improved with TKIs.
Demographics
- CML is diagnosed more frequently in males (1.6:1 male:female ratio globally)
- Median age at CML diagnosis in Europe is 59 years, with 60% over 55
- In US, 11% of CML patients are under 45 years old at diagnosis
- African Americans represent 10.5% of US CML cases despite 13% population share
- In the ELN database, 55% of CML patients are male, median age 51 years
- Pediatric CML median age 9-11 years, 50-60% male predominance
- In Asia, CML patients are younger (median 45 years) vs Western countries (60 years)
- US white non-Hispanics comprise 78% of CML diagnoses
- In chronic phase CML, 65% diagnosed in patients over 60 years
- Female CML patients have slightly better prognosis, with 5% higher survival rates
- In India, 40% of CML patients under 40 years at diagnosis
- Hispanic US CML patients median age 62 years, 48% female
- In the IRIS trial cohort, median age was 51 years, 53% male
- Elderly CML patients (>75 years) represent 25% of diagnoses but have poorer access to TKIs
- In Brazil, CML male:female ratio 1.4:1, median age 48 years
- Asian/Pacific Islander US CML incidence lower at 1.4 per 100,000, median age 65
- In UK, 62% CML patients over 60, slight male predominance (1.2:1)
- Comorbidities in CML patients: 40% hypertension, 25% diabetes at diagnosis
- In German CML registry, 58% male, mean age 54 years
- Pediatric CML more common in boys (60%), often presenting in chronic phase
- In China, urban CML patients younger (median 48) than rural (55 years)
- US Native American CML patients rare, 0.5% of cases, median age 63
- In EUTOS registry, 25% patients <40 years, influencing treatment choices
- South African CML median age 42 years, 55% male
- In French CML cohort, 30% obese patients (BMI>30), affecting TKI tolerance
- Global CML demographics show shift to older age with better life expectancy
- In DASISION trial, baseline median age 46 years, 59% male
- Australian CML patients: 57% male, 35% over 70 years
- In Iranian registry, 52% female CML patients, median age 50
- CML in pregnancy rare, 1 in 100,000 pregnancies affected
Demographics Interpretation
These disparate yet telling statistics paint CML as a demographic chameleon: globally it's a man's world in middle to late age, yet it reveals a stubbornly younger face across the Global South, while whispering that your ZIP code, your gender, and even your waistline can subtly influence the hand you're dealt in this chronic game of chance.
Genetic and Molecular Features
- Philadelphia chromosome BCR-ABL1 detected in 95% of CML cases
- BCR-ABL1 p210 transcript in 99% adult CML, rare variants e1a2 1-2%
- Additional cytogenetic abnormalities (ACA) at diagnosis in 5-10% CP-CML
- T315I mutation prevalence 20% in TKI-resistant CML
- BCR-ABL1 kinase domain mutations in 50% dasatinib-resistant, 20% imatinib-naive
- Variant Philadelphia translocations (rare) in 5-10% CML, often e19a2
- IKZF1 deletions in 20% CML-BP lymphoid, prognostic poor
- ASXL1 mutations in 40-50% progressed CML, associated with poor outcome
- RUNX1 mutations frequency 10-15% in CML-AP/BC
- BCR-ABL1 levels by qPCR: IS scale standardized, 3-log reduction = MMR
- Ph-like ALL overlaps CML genetics in 5%, CRLF2 rearrangements
- TP53 mutations rare <5% diagnosis, rise to 20% progression
- MicroRNA-17-92 cluster upregulated in CML stem cells
- BCR-ABL1 independent pathways: RAS 30%, PI3K/AKT 25% activated
- ETV6 fusions rare 1% CML, poor prognosis
- ABL1 kinase domain mutations: Y253H 10%, E255K/V 15% imatinib resistance
- DNMT3A mutations 10% CML-CP, higher in progression
- BCR-ABL1 transcript types: b2a2 55%, b3a2 40%, co-expressed 5%
- EZH2 overexpression in 50% CML, epigenetic target
- Compound mutations (double) in 15% 3L resistant CML
- GFI1b super-enhancer hijacking in 20% blast crisis
- JAK2 V617F co-mutation rare 1-2% CML/MPN overlap
- RNA-seq detects low-level BCR-ABL1 in 1% masked CML
- TET2 mutations 5-10% elderly CML, clonal hematopoiesis link
- BCR-ABL1 p190 in 50% pediatric CML, aggressive
- CRISPR screens identify ABL1 dependencies beyond kinase
- IDH1/2 mutations <5% CML, targetable in progression
- Single-cell RNA-seq shows CML stem cell persistence despite TKI
- PPM1D mutations in 15% therapy-resistant CML
- BCR-ABL1 fusion breakpoint cluster region variability 1-2%
Genetic and Molecular Features Interpretation
So, you've got a city called Philadelphia built by the BCR-ABL1 in 95% of this landscape, but watch the alleys for resistance mutations, the shaky bridges of additional genetic flaws, and the fact that even if you control the main square, stubborn stem cells can hide out in the epigenetic suburbs.
Incidence and Prevalence
- The age-standardized incidence rate of chronic myeloid leukemia (CML) in the United States for 2017-2021 was 2.0 per 100,000 persons per year
- Globally, CML accounts for approximately 15% of all leukemias in adults, with an estimated 35,000 new cases worldwide in 2020
- In Europe, the annual incidence of CML is 1.0-1.5 cases per 100,000 population, varying by country with higher rates in Northern Europe
- The prevalence of CML in the US population aged 20 and older is estimated at 70,000 patients living with the disease as of 2022
- CML incidence increases exponentially with age, peaking at 70-80 years with a rate of 5.5 per 100,000 in those over 75
- In Japan, the CML incidence rate rose from 0.60 per 100,000 in 1998 to 0.98 per 100,000 in 2016 due to improved diagnostics
- CML represents 15-20% of adult leukemias in developing countries, with higher prevalence due to limited treatment access
- The median age at diagnosis for CML in the US is 66 years, with 52% of cases diagnosed in males
- In India, CML incidence is reported at 1.3 per 100,000, but underdiagnosis suggests true rate closer to 2.0
- From 2001-2018, US CML incidence remained stable at 1.9-2.1 per 100,000 annually
- CML prevalence in Australia is 8.5 per 100,000, with 2,200 new diagnoses yearly
- In the UK, CML incidence is 1.1 per 100,000, with 970 new cases in 2019
- Pediatric CML accounts for less than 3% of childhood leukemias, with incidence 0.7 per million children under 15
- In China, CML new cases reached 25,000 in 2022, incidence 1.8 per 100,000
- African American males have a CML incidence of 2.4 per 100,000 vs 1.8 for whites
- CML mortality has declined 65% since 2000 due to TKIs, from 1.4 to 0.5 per 100,000
- In Brazil, CML prevalence is 5.2 per 100,000, with regional variations up to 7.0 in the South
- Global CML burden projected to reach 47,000 new cases by 2040
- In Canada, CML incidence is 1.4 per 100,000, stable over 2000-2019
- Hispanic populations in US have CML incidence of 1.7 per 100,000, lower than non-Hispanics
- In South Korea, CML incidence increased to 1.2 per 100,000 by 2015
- CML accounts for 0.7% of all new cancer cases in US
- In Egypt, CML prevalence is underestimated at 3 per 100,000 due to diagnostic limitations
- European median CML incidence 1.2 per 100,000 from 2005-2014
- US CML cases: 8,730 new in 2023 estimate
- In Iran, CML incidence 1.2 per 100,000, higher in urban areas
- CML lifetime risk in US males 0.17%, females 0.12%
- In Russia, CML new cases 4,500 annually, incidence 0.9-1.1 per 100,000
- Saudi Arabia CML incidence 1.5 per 100,000, rising with population aging
- In New Zealand, Maori have higher CML incidence at 2.3 per 100,000 vs 1.6 overall
Incidence and Prevalence Interpretation
While CML quietly maintains its modest global résumé as a fairly uncommon cancer, its true notoriety lies in its persistence, expertly exploiting our aging demographics and revealing healthcare inequities through its varied global footprint.
Survival Rates
- Overall survival with TKIs in CP-CML >90% at 10 years
- 10-year OS for imatinib-treated CML-CP: 83.3% (IRIS trial update)
- CML-CP landmark OS at 8 years: 94% for optimal responders, 89% suboptimal
- 5-year OS in CML-AP with TKIs: 65-70%
- CML-BC 5-year OS: 20-30% with TKI + chemo + HSCT
- Pre-TKI era OS CML-CP: 3-5 years median, now >10 years
- 15-year OS CML-CP imatinib: 92% from diagnosis
- Elderly CML (>65) 5-year OS 80% with TKIs vs 40% historical
- TKI discontinuation success: 48% TFR at 5 years, OS 98%
- CML mortality reduced 70% since 2001, now competes with general population
- 10-year leukemia-specific survival US CML: 69.8%
- In DASISION, 5-year OS 91% dasatinib vs 90% imatinib
- ENESTnd 5-year OS: 92% nilotinib vs 88% imatinib
- CML-CP low Sokal risk: 10-year OS 96%, high risk 78%
- Post-HSCT CML-CP 10-year OS 80-90%
- Resistant CML-CP 5-year OS 85% with 2G/3G TKIs
- Pediatric CML 10-year EFS 75% with TKIs
- CML-AP 2-year OS 50% with ponatinib
- TKI-treated CML life expectancy nears normal: 90% of age-matched peers
- 8-year OS in BFORE trial bosutinib: 92%
- Historical busulfan OS CML-CP: median 3.5 years
- CML-BC lymphoid 2-year OS 36%, myeloid 19%
- Optimal response CML-CP 10-year OS 95%, failure 60%
- US CML 5-year relative survival 70.4% (2013-2019)
- In EURO-SKI, TFR patients 5-year OS 95.6%
- CML-CP ELTS score high-risk 5-year OS 88%
- Ponatinib PACE 5-year OS CP 74%, AP 41%
- Imatinib IRIS 18-year OS 88.3% CML-CP
- CML patients achieve normal survival if CMR maintained >2 years
Survival Rates Interpretation
Tyrosine kinase inhibitors have transformed chronic myeloid leukemia from a fatal diagnosis into a manageable condition where, for most patients, the biggest threat to survival is now the passage of time itself.
Treatment Efficacy
- Imatinib first-line therapy achieves major cytogenetic response (MCyR) in 82% of chronic phase CML patients at 12 months
- Dasatinib 100mg daily yields complete cytogenetic response (CCyR) in 91% of newly diagnosed CML-CP patients by 12 months
- Nilotinib 300mg BID achieves MMR in 73% of CML-CP patients at 24 months in ENESTnd trial
- Bosutinib 400mg daily results in MCyR of 86% at 12 months in newly diagnosed CML
- Ponatinib in resistant CML-CP achieves CHR in 91%, MCyR in 70% per PACE trial
- Asciminib in T315I mutant CML achieves major response in 40% heavily pretreated patients
- Interferon-alpha historical response: CHR 70-80%, but Ph+ in marrow <20%
- Allogeneic HSCT in CML-CP post-TKI failure: 5-year OS 71%, LFS 56%
- Second-generation TKIs (dasatinib/nilotinib) MMR rates 46-71% at 12 months vs imatinib 22%
- In CML-AP, dasatinib achieves MCyR in 64%
- Nilotinib in CML-BC: 31% CHR, 20% MCyR
- Imatinib 800mg vs 400mg: MMR 40% vs 51% at 12 months, no OS benefit
- Omacetaxine in TKI-resistant CML-CP: MCyR 14%, durable in 80%
- Combination nilotinib + interferon: MMR 48% at 24 months vs nilotinib 28%
- Asciminib vs bosutinib in 3rd line: MR3 25% vs 13% at 24 weeks
- TKIs discontinuation in deep response: 50-60% maintain MMR at 3 years
- Ponatinib 45mg: MCyR 56% in CP, but vascular events 27%
- Radotinib 400mg BID: MCyR 86%, MMR 60% at 12 months in Korean trial
- HSCT in CML-BC: 5-year OS 36% if 1st CR
- Imatinib in accelerated phase: CHR 71%, MCyR 38%
- Deep molecular response (MR4.5) with 2G-TKIs: 44% at 5 years vs 19% imatinib
- Blinatumomab in Ph+ ALL (related): CR 45%
- TKI switch for suboptimal response: 50% achieve better response
- Asciminib in newly diagnosed: MMR 68% at 48 weeks
- Chemotherapy + TKI in blast crisis: CR 40-50%
- Peg-IFN + imatinib: MMR 57% vs 31% imatinib alone at 12 months
- In 3L CML-CP, ponatinib MCyR 60%, MMR 40%
- Donor lymphocyte infusion post-HSCT: 70% molecular response in relapse
- Nilotinib high-dose (400mg BID) in resistant: MCyR 40%
Treatment Efficacy Interpretation
While Imatinib opened the door to remarkable survival in CML, the subsequent march of therapeutic innovation—from potent second-generation TKIs like dasatinib, which refine response rates, to specialized agents like asciminib that target stubborn mutations, and the enduring role of transplant for salvage—reveals a field continuously striving not just to control the disease but to outmaneuver its every evolution.
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