Name

Chronic myeloid leukemia, BCR-ABL1-positive

ICD-O-2 Morphology

9863/3: Chronic myeloid leukemia, NOS

ICD-O-3 Morphology

9875/3: Chronic myelogenous leukemia, BCR/ABL1 positive
Effective 2001 and later

Reportable

for cases diagnosed 2001 and later

Primary Site(s)

C421
Primary site must be bone marrow (C421)

Grade

Not Applicable

Module Rule

None

Alternate Names

Chronic granulocytic leukemia, BCR/ABL1
Chronic granulocytic leukemia, BCR-ABL [OBS]
Chronic granulocytic leukemia, Philadelphia chromosome, (Ph+) positive [OBS]
Chronic granulocytic leukemia, t(9;22)(q34;q11)
Chronic myelogenous leukemia, BCR-ABL1 positive
Chronic myelogenous leukemia, Philadelphia chromosome, (Ph+) positive [OBS]
Chronic myelogenous leukemia, Philadelphia chromosome, t(9;22)(q34;q11), BCR-ABL positive [OBS]
Chronic myelogenous leukemia, t(9;22)(q34;q11) [OBS]
Chronic myelogenous leukemia, t(9;22)(q34;q11.2) [OBS]
Chronic myeloid leukemia-Accelerated phase
CML, Accelerated phase (AP)
CML, BCR-ABL1+
CML, Blast Phase (BP)
CML, Chronic Phase (CP)

Definition

Chronic myeloid leukemia (CML), BCR-ABL1-positive, is a myeloproliferative neoplasm (MPN) in which granulocytes are the major proliferative component. It arises in a hematopoietic stem cell and is characterized by the chromosomal translocation t(9;22)(q34.1;q11.2), which results in the formation of the Philadelphia (Ph) chromosome, containing the BCR-ABL1 fusion gene.

CML has four phases:
1. Accelerated phase - can last weeks to months.
2. Chronic phase - involvement is usually limited to blood, bone marrow and spleen, although the liver may be infiltrated.
3. Blastic phase - lymph nodes and tissue may be involved. The blastic phase is a progression from the chronic phase. It remains the same histology: Chronic myelogenous leukemia.
4. Terminal phase - last phase and survival is usually only weeks or months

Criteria for CML, accelerated phase:
CML, accelerated phase criteria
Any 1 or more of the following hematologic/cytogenetic criteria or response-to-TKI criteria:
• Persistent or increasing WBC (.10 3 109/L), unresponsive to therapy “Provisional” response-to-TKI criteria
• Persistent or increasing splenomegaly, unresponsive to therapy
• Hematologic resistance to the first TKI (or failure to
achieve a complete hematologic response* to the first
TKI) or
• Persistent thrombocytosis (.1000 3 109/L), unresponsive to therapy • Any hematological, cytogenetic, or molecular indications
of resistance to 2 sequential TKIs or
• Persistent thrombocytopenia (,100 3 109/L) unrelated to therapy • Occurrence of 2 or more mutations in BCR-ABL1 during
TKI therapy
• 20% or more basophils in the PB
• 10%-19% blasts† in the PB and/or BM
• Additional clonal chromosomal abnormalities in Ph1 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 Ph1 cells that occurs during therapy

Abstractor Notes

Diagnosis of this neoplasm is usually incidental (85% are asymptomatic when diagnosed) when the patient has a CBC and/or peripheral blood smear. If the results of the WBC are abnormal (elevated) the physician will order a bone marrow aspiration.

Treatment information:
Chronic phase:
Tyrosine kinase inhibitor; high-dose chemotherapy with donor cell transplant; BRM (interferon) with or without chemotherapy. May also have single or multi-agent chemotherapy and splenectomy.

Accelerated phase:
Donor stem cell transplant; tyrosine kinase inhibitor; BRM (interferon) with or without chemotherapy.

Blast phase:
Tyrosine kinase inhibitor; single or multi-drug chemotherapy; donor stem cell transplant.

Surgery includes splenectomy.

Aspirin was previously documented as treatment for this disease. This was found to be incorrect. Treatment has been updated based on the NCI website (updated 6/12/15)

Definitive Diagnostic Methods

Bone marrow biopsy
FISH
Genetic testing
Polymerase chain reaction (PCR)

Genetics Data

9q34.1
22q11.2
BCR-ABL1
Ph chromosome, del(22) t(9;22)
t(9;22)(q34.1;q11.2)

Immunophenotyping

CD2, CD3, CD4, CD5, CD7, CD8 (T-cell related antigens)
CD10, CD19, CD79a, PAX50 (B-cell related antigens)
CD11b expression lacking
CD11c expression
CD13 expression
CD14 expression
CD15 expression
CD33 expression
CD34 positive
CD41 expression
CD56 expression lacking
CD61 expression
Glycophorin A and C expression
KIT (CD117) expression

Treatments

Chemotherapy
Hematologic Transplant and/or Endocrine Procedures
Immunotherapy
Surgery

Transformations from

None

Corresponding ICD-9 Codes

205.1 Chronic myeloid leukemia

Corresponding ICD-10 Codes

C92.1 Chronic myeloid leukemia

Corresponding ICD-10-CM Codes (U.S. only)

C92.1 Chronic myeloid leukemia, BCR/ABL-positive (effective October 01, 2015)

Signs and Symptoms

Abnormal white blood count
Bleeding complications/thrombotic
Destructive bone lesions/bone pain
Night sweats
Progressive leukocytosis
Thrombocytosis
Weight loss

Progression and Transformation

Progression to the acute and blast phases

Epidemiology and Mortality

Age: 50-60 years median age
Incidence: 1-2 cases per 100,000 population
Sex: Slight male predominance
Survival: 2-3 years (median), 4 years with conventional chemotherapy

Sources

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition)
IARC: Lyon 2017
Section: Myeloproliferative neoplasms
Pages: 30-36

International Classification of Diseases for Oncology, Third Edition, First Revision. Geneva: World Health Organization, 2013.
Section: ICD-O-3.1 (2011) Morphological Codes
Pages: http://codes.iarc.fr/codegroup/2

National Cancer Institute
Section: General Information About Myeloproliferative Neoplasms
Pages: https://www.cancer.gov/types/myeloproliferative/hp/mds-mpd-treatment-pdq
Glossary