Chronic myelogenous leukemia (CML) is a type of blood cancer characterized by uncontrolled growth of myeloid cells in the bone marrow. Symptoms of CML may include fatigue, weakness, weight loss, night sweats, fever, abdominal discomfort from an enlarged spleen, and easy bruising or bleeding. Diagnosis typically involves blood tests, including a complete blood cell count to detect abnormal white blood cell, red blood cell, and platelet counts, as well as genetic testing to identify the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene), which is characteristic of CML. Bone marrow biopsy also may be performed for confirmation.
Individuals diagnosed with CML should receive thorough evaluation and appropriate management. Significant advancements in the management of CML have led to a life expectancy similar to that of the general population for persons treated early with currently recommended therapies.
Here are five things to know about CML.
1. CML treatment aims to achieve durable remission, manage symptoms, and improve quality of life.
Pharmacological agents such as the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, nilotinib, and bosutinib are standard first-line therapies. Eventual toxicity or resistance pathways has led to the development of novel medications like ponatinib and asciminib that have improved outcomes for patients resistant to or intolerant of first- and second-generation TKIs. Combination therapy, including TKI combinations or TKIs with immunotherapy, may enhance treatment efficacy.
Transplantation options such as bone marrow or hematopoietic stem cell transplantation are considered for eligible patients, offering potential cure but with associated risks. Treatment-free remission allows some patients to discontinue TKI therapy under close monitoring, with psychological effects being an important consideration. Emerging treatments include monoclonal antibodies, CAR T-cell therapy, drugs targeting resistance mutations, and epigenetic modifications, as well as personalized genomic sequencing and novel drug delivery systems. These advancements offer hope for improved outcomes and personalized care in CML management.
2. Complications from CML and its treatments can significantly affect patients' quality of life and overall prognosis.
CML and associated therapeutic interventions can lead to various complications that affect patients' well-being and disease outlook. Secondary treatment-related cancers, arising from chemotherapy or radiation therapy, present long-term risks for individuals undergoing CML treatment. The psychosocial impact of chronic illness, encompassing stress and anxiety linked to treatment adverse effects and long-term prognosis, can significantly amplify patient distress and diminish quality of life. Moreover, CML-related complications such as hepatomegaly, splenomegaly, worsening anemia, platelet count changes leading to clotting or bleeding complications, recurrent infections, bone pain, and fever can substantially compromise physical health and functional status. Adverse effects from drugs used in CML treatment, notably TKIs, may manifest as gastrointestinal symptoms, fatigue, rash, and musculoskeletal pain, necessitating vigilant monitoring and management. Early and comprehensive management of treatment complications, including meticulous monitoring of blood cell counts during initial therapy, is of paramount importance to optimizing outcomes and mitigating risks in individuals with CML.
3. CML accounts for approximately 15% of adult leukemia cases, with an estimated annual incidence of 1-2 cases per 100,000 individuals worldwide.
CML is a blood cancer characterized by uncontrolled growth of myeloid cells in the bone marrow. Although CML can affect individuals of any age, the median age at diagnosis is approximately 60 years, with a wide range of presentation from childhood to older adulthood. Despite its occurrence across diverse demographics, certain patterns emerge in its epidemiology.
In developed countries, such as the United States and those in Europe, CML prevalence is higher than in developing regions. This may be attributed to better access to healthcare services, leading to more frequent diagnosis and detection of the disease. Additionally, advancements in medical technology and awareness of CML among healthcare professionals in developed regions may contribute to the higher prevalence rates.
The introduction of TKI therapy has revolutionized the treatment landscape for CML, significantly improving survival rates. With TKIs, the 5-year survival rate for CML now exceeds 80%, marking a substantial increase from previous decades. This improvement underscores the importance of early detection, prompt treatment initiation, and ongoing management in enhancing patient outcomes.
Sex disparities exist in CML incidence, with a slightly higher prevalence observed in males than in females. Although the reasons for this discrepancy are not fully understood, hormonal differences and genetic factors may play a role in predisposing males to CML development. Race also influences CML prevalence, with individuals of European descent having a higher incidence compared with other racial groups. However, CML can affect individuals of any race, indicating the need for awareness and access to diagnostic and treatment resources across diverse populations.
Sociodemographic factors such as access to healthcare, socioeconomic status, and geographical location can affect disease incidence, diagnosis, and treatment outcomes in patients with CML. Disparities in healthcare access and resources may contribute to delayed diagnosis, inadequate treatment, and poorer prognosis in certain demographic groups. Overall, understanding the epidemiology of CML helps guide public health strategies, resource allocation, and efforts to improve access to care for all individuals affected by this disease. By addressing disparities and promoting early detection and effective treatment, healthcare systems can continue to advance outcomes and quality of life for patients with CML worldwide.
4. Diagnosing CML involves a comprehensive evaluation of clinical signs, laboratory tests, and molecular studies.
Patients may present with nonspecific symptoms such as fatigue, weakness, weight loss, night sweats, and abdominal discomfort due to splenomegaly resulting from increased production of abnormal myeloid cells. Hypermetabolism-related symptoms, including fever and unintentional weight loss, also may be observed. Initial diagnostic tests typically include a complete blood cell count with differential, which may reveal an elevated white blood cell count, anemia, and thrombocytosis. A peripheral blood smear allows visual examination of blood cells, revealing the presence of immature myeloid cells and characteristic morphologic changes.
Confirmation of CML diagnosis often requires bone marrow analysis, including bone marrow aspiration and biopsy. Histopathologic examination of bone marrow samples helps to assess cell morphology, proliferation, and differentiation. Molecular studies, such as fluorescence in situ hybridization or polymerase chain reaction, are essential for detecting the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene), a hallmark genetic abnormality in CML. Identification of the Philadelphia chromosome confirms the diagnosis of CML and helps guide treatment decisions, including the use of TKIs as frontline therapy.
5. Managing CML during pregnancy poses unique challenges owing to concerns about the potential effects of treatment on both the mother and the developing fetus.
Pregnancy outcomes in women with CML may be influenced by factors such as disease stage, overall health, and treatments received. Preterm birth, low birth weight, and preeclampsia are potential risks, necessitating close monitoring by a multidisciplinary team consisting of hematologists, obstetricians, and maternal-fetal medicine specialists.
The effects of CML treatments, particularly TKIs, on the fetus are a significant concern. Although less effective treatments may be considered to minimize fetal exposure, they also carry risks for disease progression in the mother. In some cases, treatment may be deferred until after delivery, especially if the CML is in the chronic phase and inactive or in remission, to reduce potential harm to the fetus. Breastfeeding also may pose complications owing to the potential transfer of medications to the infant through breast milk. Overall, managing CML during pregnancy requires careful consideration of risks and benefits, close monitoring, and individualized treatment decisions to optimize outcomes for both the mother and the baby.
COMMENTARY
Chronic Myelogenous Leukemia (CML): 5 Things to Know
Adam Braun, MD
DISCLOSURES
| April 23, 2024Chronic myelogenous leukemia (CML) is a type of blood cancer characterized by uncontrolled growth of myeloid cells in the bone marrow. Symptoms of CML may include fatigue, weakness, weight loss, night sweats, fever, abdominal discomfort from an enlarged spleen, and easy bruising or bleeding. Diagnosis typically involves blood tests, including a complete blood cell count to detect abnormal white blood cell, red blood cell, and platelet counts, as well as genetic testing to identify the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene), which is characteristic of CML. Bone marrow biopsy also may be performed for confirmation.
Individuals diagnosed with CML should receive thorough evaluation and appropriate management. Significant advancements in the management of CML have led to a life expectancy similar to that of the general population for persons treated early with currently recommended therapies.
Here are five things to know about CML.
1. CML treatment aims to achieve durable remission, manage symptoms, and improve quality of life.
Pharmacological agents such as the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, nilotinib, and bosutinib are standard first-line therapies. Eventual toxicity or resistance pathways has led to the development of novel medications like ponatinib and asciminib that have improved outcomes for patients resistant to or intolerant of first- and second-generation TKIs. Combination therapy, including TKI combinations or TKIs with immunotherapy, may enhance treatment efficacy.
Transplantation options such as bone marrow or hematopoietic stem cell transplantation are considered for eligible patients, offering potential cure but with associated risks. Treatment-free remission allows some patients to discontinue TKI therapy under close monitoring, with psychological effects being an important consideration. Emerging treatments include monoclonal antibodies, CAR T-cell therapy, drugs targeting resistance mutations, and epigenetic modifications, as well as personalized genomic sequencing and novel drug delivery systems. These advancements offer hope for improved outcomes and personalized care in CML management.
2. Complications from CML and its treatments can significantly affect patients' quality of life and overall prognosis.
CML and associated therapeutic interventions can lead to various complications that affect patients' well-being and disease outlook. Secondary treatment-related cancers, arising from chemotherapy or radiation therapy, present long-term risks for individuals undergoing CML treatment. The psychosocial impact of chronic illness, encompassing stress and anxiety linked to treatment adverse effects and long-term prognosis, can significantly amplify patient distress and diminish quality of life. Moreover, CML-related complications such as hepatomegaly, splenomegaly, worsening anemia, platelet count changes leading to clotting or bleeding complications, recurrent infections, bone pain, and fever can substantially compromise physical health and functional status. Adverse effects from drugs used in CML treatment, notably TKIs, may manifest as gastrointestinal symptoms, fatigue, rash, and musculoskeletal pain, necessitating vigilant monitoring and management. Early and comprehensive management of treatment complications, including meticulous monitoring of blood cell counts during initial therapy, is of paramount importance to optimizing outcomes and mitigating risks in individuals with CML.
3. CML accounts for approximately 15% of adult leukemia cases, with an estimated annual incidence of 1-2 cases per 100,000 individuals worldwide.
CML is a blood cancer characterized by uncontrolled growth of myeloid cells in the bone marrow. Although CML can affect individuals of any age, the median age at diagnosis is approximately 60 years, with a wide range of presentation from childhood to older adulthood. Despite its occurrence across diverse demographics, certain patterns emerge in its epidemiology.
In developed countries, such as the United States and those in Europe, CML prevalence is higher than in developing regions. This may be attributed to better access to healthcare services, leading to more frequent diagnosis and detection of the disease. Additionally, advancements in medical technology and awareness of CML among healthcare professionals in developed regions may contribute to the higher prevalence rates.
The introduction of TKI therapy has revolutionized the treatment landscape for CML, significantly improving survival rates. With TKIs, the 5-year survival rate for CML now exceeds 80%, marking a substantial increase from previous decades. This improvement underscores the importance of early detection, prompt treatment initiation, and ongoing management in enhancing patient outcomes.
Sex disparities exist in CML incidence, with a slightly higher prevalence observed in males than in females. Although the reasons for this discrepancy are not fully understood, hormonal differences and genetic factors may play a role in predisposing males to CML development. Race also influences CML prevalence, with individuals of European descent having a higher incidence compared with other racial groups. However, CML can affect individuals of any race, indicating the need for awareness and access to diagnostic and treatment resources across diverse populations.
Sociodemographic factors such as access to healthcare, socioeconomic status, and geographical location can affect disease incidence, diagnosis, and treatment outcomes in patients with CML. Disparities in healthcare access and resources may contribute to delayed diagnosis, inadequate treatment, and poorer prognosis in certain demographic groups. Overall, understanding the epidemiology of CML helps guide public health strategies, resource allocation, and efforts to improve access to care for all individuals affected by this disease. By addressing disparities and promoting early detection and effective treatment, healthcare systems can continue to advance outcomes and quality of life for patients with CML worldwide.
4. Diagnosing CML involves a comprehensive evaluation of clinical signs, laboratory tests, and molecular studies.
Patients may present with nonspecific symptoms such as fatigue, weakness, weight loss, night sweats, and abdominal discomfort due to splenomegaly resulting from increased production of abnormal myeloid cells. Hypermetabolism-related symptoms, including fever and unintentional weight loss, also may be observed. Initial diagnostic tests typically include a complete blood cell count with differential, which may reveal an elevated white blood cell count, anemia, and thrombocytosis. A peripheral blood smear allows visual examination of blood cells, revealing the presence of immature myeloid cells and characteristic morphologic changes.
Confirmation of CML diagnosis often requires bone marrow analysis, including bone marrow aspiration and biopsy. Histopathologic examination of bone marrow samples helps to assess cell morphology, proliferation, and differentiation. Molecular studies, such as fluorescence in situ hybridization or polymerase chain reaction, are essential for detecting the presence of the Philadelphia chromosome (BCR-ABL1 fusion gene), a hallmark genetic abnormality in CML. Identification of the Philadelphia chromosome confirms the diagnosis of CML and helps guide treatment decisions, including the use of TKIs as frontline therapy.
5. Managing CML during pregnancy poses unique challenges owing to concerns about the potential effects of treatment on both the mother and the developing fetus.
Pregnancy outcomes in women with CML may be influenced by factors such as disease stage, overall health, and treatments received. Preterm birth, low birth weight, and preeclampsia are potential risks, necessitating close monitoring by a multidisciplinary team consisting of hematologists, obstetricians, and maternal-fetal medicine specialists.
The effects of CML treatments, particularly TKIs, on the fetus are a significant concern. Although less effective treatments may be considered to minimize fetal exposure, they also carry risks for disease progression in the mother. In some cases, treatment may be deferred until after delivery, especially if the CML is in the chronic phase and inactive or in remission, to reduce potential harm to the fetus. Breastfeeding also may pose complications owing to the potential transfer of medications to the infant through breast milk. Overall, managing CML during pregnancy requires careful consideration of risks and benefits, close monitoring, and individualized treatment decisions to optimize outcomes for both the mother and the baby.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
TOP PICKS FOR YOU