What are the key differences in presentation and treatment between Chronic Myeloid Leukemia (CML) and Acute Myeloid Leukemia (AML)?

From the Guidelines

Chronic Myeloid Leukemia (CML) and Acute Myeloid Leukemia (AML) are two distinct types of leukemia with different presentations, progressions, and treatment approaches, with CML typically presenting more gradually and AML manifesting rapidly with severe symptoms. The key differences in presentation and treatment between CML and AML can be summarized as follows:

• CML typically presents with fatigue, weight loss, and splenomegaly, while AML manifests with high fever, significant bleeding, and frequent infections due to profound cytopenias.
• The hallmark of CML is the Philadelphia chromosome (BCR-ABL fusion gene), which is targeted with tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, or dasatinib as first-line treatments, as recommended by the European LeukemiaNet 2020 guidelines 1.
• In contrast, AML requires immediate, intensive chemotherapy, typically beginning with induction using cytarabine and an anthracycline like daunorubicin or idarubicin, followed by consolidation therapy, as outlined in the ESMO minimum clinical recommendations for diagnosis, treatment, and follow-up of acute myeloblastic leukemia (AML) in adult patients 1.
• AML treatment may culminate in stem cell transplantation for eligible patients, whereas CML treatment focuses on achieving a stable deep molecular response and discontinuing medication for treatment-free remission (TFR) 1.
• The different approaches reflect the diseases' underlying biology: CML involves a specific genetic abnormality driving slow proliferation of relatively mature cells, while AML represents a rapid accumulation of immature myeloid cells with diverse genetic mutations, requiring more aggressive intervention to prevent rapid progression and death. Some key points to consider in the treatment of CML and AML include:
• Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score for CML 1.
• Monitoring of response should be done by quantitative polymerase chain reaction whenever possible for CML 1.
• A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached in CML 1.
• Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML 1.
• Treatment discontinuation may be considered in patients with durable deep molecular response with the goal of achieving TFR in CML 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Presentation of CML and AML

• Chronic Myeloid Leukemia (CML) is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2, resulting in the Philadelphia chromosome 2, 3, 4.
• Acute Myeloid Leukemia (AML) is a distinct entity, with BCR-ABL-positive AML being a rare subtype, accounting for a small percentage of AML cases 5.
• CML typically presents in the chronic phase, with patients often being asymptomatic or experiencing mild symptoms, whereas AML presents acutely, with symptoms such as fatigue, weight loss, and bleeding complications.

Treatment of CML and AML

• The treatment of CML typically involves tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, bosutinib, and nilotinib, which target the BCR-ABL fusion protein 2, 3, 4.
• In AML, treatment usually involves intensive chemotherapy, with or without allogeneic stem cell transplantation, and the use of TKIs such as imatinib, dasatinib, or nilotinib may be considered in certain cases, particularly in BCR-ABL-positive AML 5.
• Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML who have failed at least two TKIs and for all patients with advanced-phase disease 2, 3, 4.

Key Differences between CML and AML

• The presence of the Philadelphia chromosome is a hallmark of CML, whereas AML is characterized by a variety of genetic abnormalities 2, 3, 4, 5.
• CML typically has a more indolent course, with a longer chronic phase, whereas AML is often aggressive and requires prompt treatment 2, 3, 4, 5.
• The treatment approaches for CML and AML differ, with CML often being managed with TKIs and AML requiring intensive chemotherapy and/or allogeneic stem cell transplantation 2, 3, 4, 5.