Unifying Concepts

Accelerated Phase Criteria for Chronic Myeloid Leukemia (CML)

The chronic myeloid leukemia (CML) is classically staged into chronic phase (CP, most patients at presentation), accelerated phase (AP) and blast phase (BP). Many definitions have been used for these stages, but all the data generated from the tyrosine kinase inhibitor (TKI) studies has used the historically standard definition where AP is defined by the presence of one or more of the following: ≥15% blasts in PB/BM, ≥20% basophils in PB, platelets <100,000/µL unrelated to treatment or the development of cytogenetic evolution. Blast phase is defined by the presence of ≥30% blasts in the peripheral blood or bone marrow, the presence of clusters of blasts in marrow or the presence of extramedullary disease with immature cells (i.e., a myeloid sarcoma).

With regard to chronic myeloid leukemia (CML), BCR-ABL1+, most cases of CML in chronic phase can be diagnosed from peripheral blood (PB) findings combined with detection of t(9;22)(q34.1;q11.2) or, more specifically, BCR-ABL1 by molecular genetic techniques. However, a bone marrow (BM) aspirate is essential to ensure sufficient material for a complete karyotype and for morphologic evaluation to confirm the phase of disease. In the era of tyrosine-kinase inhibitor (TKI) therapy, newly diagnosed patients may have a nearly normal lifespan, but regular monitoring for BCR-ABL1 burden and for evidence of genetic evolution and development of resistance to TKI therapy is essential to detect disease progression. Although the accelerated phase (AP) of CML is becoming less common in the era of TKI therapy, there are no universally accepted criteria for its definition. The criteria for AP in the revised WHO classification include hematologic, morphologic, and cytogenetic parameters which are supplemented by additional parameters usually attributed to genetic evolution, and manifested by evidence of resistance to TKIs. These latter “response to TKI therapy” criteria for AP are considered as “provisional” until further supported by additional data. Diagnosis of blast phase (BP) still requires either at least 20% blasts in the blood or BM or the presence of an extramedullary accumulation of blasts. However, because the onset of lymphoid BP may be quite sudden, the detection of any bona fide lymphoblasts in the blood or marrow should raise concern for a possible impending lymphoid BP, and prompt additional laboratory and genetic studies to exclude this possibility.


Criteria for CML, accelerated phase

Any 1 or more of the following hematologic/cytogenetic criteria or response-to-tyrosine-kinase inhibitor (TKI) criteria:

  • Persistent or increasing WBC (>10 x 109/L), unresponsive to therapy
  • Persistent or increasing splenomegaly, unresponsive to therapy
  • Persistent thrombocytosis (>1000 x 109/L), unresponsive to therapy
  • Persistent thrombocytopenia (<100 x 109/L) unrelated to therapy
  • 20% or more basophils in the PB
  • 10%-19% blasts† in the PB and/or BM
  • Additional clonal chromosomal abnormalities in Ph+ cells at diagnosis that include “major route” abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype, or abnormalities of 3q26.2
  • Any new clonal chromosomal abnormality in Ph+ cells that occurs during therapy

“Provisional” response-to-TKI criteria

  • Hematologic resistance to the first TKI (or failure to achieve a complete hematologic response* to the first TKI) or
  • Any hematological, cytogenetic, or molecular indications of resistance to 2 sequential TKIs or
  • Occurrence of 2 or more mutations in BCR-ABL1 during TKI therapy

Large clusters or sheets of small, abnormal megakaryocytes, associated with marked reticulin or collagen fibrosis in biopsy specimens may be considered as presumptive evidence of AP, although these findings are usually associated with 1 or more of the criteria listed above.
*Complete hematologic response: WBC, <10 x 109/L; platelet count, <450 x 109/L, no immature granulocytes in the differential, and spleen nonpalpable.
†The finding of bona fide lymphoblasts in the blood or marrow, even if <10%, should prompt concern that lymphoblastic transformation may be imminent and warrants further clinical and genetic investigation; 20% or more blasts in blood or BM, or an infiltrative proliferation of blasts in an extramedullary site is CML, blast phase.



  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. [Medline]
  2. Morita K, Sasaki K. Current status and novel strategy of CML. Int J Hematol. 2021 Mar 29. [Medline]


Created Apr 15, 2021

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