What Are the WHO, ICC, and ELN CML Phase Definitions?

When you are diagnosed with Philadelphia-positive chronic myeloid leukemia (CML), your doctor will determine the “phase” of your disease. However, medical experts use three different classification systems to define these phases: the World Health Organization (WHO) 5th edition, the International Consensus Classification (ICC), and the European LeukemiaNet (ELN). The main difference between these systems is how they define the accelerated phase and the exact percentage of leukemia cells (blasts) required to diagnose the blast phase ^[1][2]. Because these guidelines place the boundaries at different percentages, a patient might be classified as being in the accelerated phase under one system, but in the chronic or blast phase under another ^[1][2].

Why Are There Different Systems?

The three systems were created for slightly different purposes, which explains why their definitions differ:

• WHO (5th Edition, 2022): This is a pathology and disease classification system. It focuses heavily on the biology of the leukemia cells and recently shifted to a simplified framework ^[3].
• ELN (2020): This is a clinical management framework designed by leukemia specialists to guide treatment decisions based on how the disease behaves in a patient over time ^[4].
• ICC (2022): This system attempts to bridge the gap between strict pathology rules and clinical treatment guidelines ^[5].

The Accelerated Phase Debate

Traditionally, CML has been divided into three phases: chronic, accelerated, and blast. Today, the systems disagree on whether the accelerated phase is still a useful label:

• WHO completely eliminated the accelerated phase in its 2022 update ^[3][1]. Instead of grouping patients with 10-19% blasts into an accelerated category, the WHO classifies them as being in the chronic phase but requires doctors to document high-risk features so that the patient’s individual risk can be assessed ^[3][1]. The WHO now recognizes only two phases: chronic and blast ^[1].
• ICC retains the accelerated phase, defining it primarily by a blast count of 10% to 19% in the blood or bone marrow ^[5][2].
• ELN also retains the traditional accelerated phase, but sets the threshold slightly higher, requiring 15% to 29% blasts ^[2][4].

Defining the Blast Phase

The blast phase (often called blast crisis) is the most advanced stage of CML, where immature leukemia cells rapidly multiply.

• Blast Thresholds: Both the WHO and the ICC define the blast phase as having 20% or more blasts in the blood or bone marrow ^[2][1]. The ELN guidelines, however, use a higher threshold of 30% or more blasts ^[4][2].
• Extramedullary Disease: All three systems agree that if there is a confirmed proliferation of blasts forming tumors outside of the bone marrow (such as in the skin or lymph nodes)—a condition known as extramedullary blast proliferation—the disease is classified as blast phase, regardless of the blast percentage in the marrow itself ^[6][4][3]. Note that this requires a confirmed blast tumor, not just an enlarged spleen.

Other Signs of Advanced Disease

In addition to counting blasts, the ICC and ELN systems use other markers to identify accelerated or advanced disease ^[2][4]:

• Basophils: Having 20% or more basophils (a specific type of white blood cell) in the blood is considered a sign of accelerated phase under both ICC and ELN ^[2][4].
• Platelets: Persistent platelet counts that are abnormally low (under 100,000) and not caused by treatment, or persistently high (over 1,000,000) and unresponsive to treatment, are criteria for the accelerated phase in both the ICC and ELN frameworks ^[2][4].
• Additional Chromosome Changes (ACAs): As CML progresses, the leukemia cells can acquire extra chromosomal abnormalities (cytogenetic changes) alongside the original Philadelphia chromosome—a process called clonal evolution ^[7][4]. This is different from a gene mutation. The ICC and ELN use the presence of clonal evolution (acquiring these ACAs) as a criterion for the accelerated phase ^[5][4]. High-risk ACAs (such as an extra chromosome 8, a second Philadelphia chromosome, or a complex karyotype) are warning signs of aggressive disease ^[7][4].

What This Means for Your Care

If your blast count falls in the “gray zone” between definitions, the label you receive will depend on the system your clinic uses. For example, assuming no other advanced features (like platelet issues or ACAs) are present:

• A patient with 12% blasts is in the accelerated phase under ICC, but in the chronic phase under ELN. The WHO would classify this as chronic phase, while noting the 12% blasts for risk assessment ^[2][1][3].
• A patient with 25% blasts is in the blast phase under WHO and ICC, but still in the accelerated phase under ELN ^[2][4][1].

While phase labels are important for determining prognosis, urgency, and clinical trial eligibility, the label alone does not dictate your entire care plan ^[1]. Your treatment is heavily guided by the biological behavior of your disease—such as specific cytogenetic findings, whether you have BCR::ABL1 mutations, and how well you respond to tyrosine kinase inhibitors (TKIs) ^[1][8]. Because these phase labels can be confusing, clinicians are encouraged to clearly document your exact blast percentage, basophil count, cytogenetic changes, and treatment response ^[1][9]. High-risk or progressing disease requires urgent expert review and an adjusted treatment strategy, which may include combination therapy or preparing for a stem cell transplant, regardless of the classification system used ^[4][1].