Clinical Reference
Blood Disorder Information
Comprehensive clinical information authored by Dr. Suparno Chakrabarti and Dr. Mahak Agarwal.
Chronic Myeloid Leukemia (CML)
Pediatric BMT — Dr. Mahak Agarwal
Chronic Myeloid Leukemia (CML) in Children
A slowly progressing disease in which too many white blood cells (not lymphocytes) are made in the bone marrow. Chronic Myeloid Leukemia was the first disease where the molecular abnormality leading to cancer was deciphered. A unique translocation between chromosomes 9 and 22 leads to the formation of BCR-ABL fusion protein which results in uncontrolled proliferation of white blood cells.
Phases of Chronic Myeloid Leukemia
- Chronic phase: elevated blood counts with enlarged spleen. Patients are asymptomatic or mildly symptomatic.
- Accelerated Phase: The disease starts getting out of hand. The spleen gets bigger despite treatment. The blasts in the blood and marrow start to increase (10 to 19%).
- Blast Crisis: This is when the disease develops to a full blown leukaemia with marrow blasts more than 20%.
What Causes Chronic Myeloid Leukaemia?
This is largely unknown as in most cases of leukaemia. Risk factors: More common in males; More common in the elderly with a median age at diagnosis of 65 years; Exposure to ionising radiation; Low Immunity; Inflammatory bowel conditions, such as ulcerative colitis or Crohn's disease; Using pesticides at work.
How is CML in Children different from that in Adults?
- CML is less common in children
- Long term outcome of TKI therapy is not known in children. We are not talking of 10 or 20 years of treatment but for 50 to 60 years or more.
- BMT should still be considered in children as first line therapy if the right donor is identified.
In most patients there are no symptoms, 25% of the patients are detected when the disease has progressed to accelerated or blast phase. Common symptoms include: Frequent Infections; Weight loss; Tiredness and looking pale; Swollen lymph glands; Abnormal bruising or bleeding; Abdominal discomfort due to an enlarged spleen; Poor appetite; Sweating at night; Headaches; Bone pain.
Diagnosis
Complete Blood Count: high white blood cell count with low haemoglobin and high platelet count. Bone Marrow Examination: necessary for confirmation; in chronic phase, blast count is less than 5%. Flow Cytometry: to confirm type of transformation. Cytogenetics: essential for confirmation of diagnosis. Karyotyping: establishes classic translocation between chromosomes 9 and 22. PCR: a test done on the DNA and establishes the amount of BCR/ABL product.
Treatment
Targeted therapy; Chemotherapy; Biologic therapy; High-dose chemotherapy with Bone Marrow Transplant.
BMT was the treatment of choice for Chronic Myeloid Leukemia until Tyrosine Kinase Inhibitors (TKI) were developed.
When is BMT needed?
- When patients stop responding to Tyrosine Kinase Inhibitors (TKI)
- When Chronic Myeloid Leukemia is in Accelerated Phase or Blast Crisis.
Conditioning
High to Moderate dose of chemotherapy is generally used in conditioning for BMT in younger patients.
Who can be a donor?
Although, a matched family donor is preferred, a Half matched (Haploidentical) family donor or an unrelated donor can also be used. However a Haploidentical (Half Matched) Donor who has Natural Killer Cell mismatch with the patient is an ideal donor for CML as it reduces the risk of relapse.
Results of BMT in CML
BMT remains the only curative treatment for Chronic Myeloid Leukemia.
- Chronic Phase: 90% are cured
- Accelerated Phase: 40-60% are cured
- Blast Crisis: 20-40% are cured
Adult BMT — Dr. Suparno Chakrabarti
Chronic Myeloid Leukemia (CML) in Adults
A slowly progressing disease in which too many white blood cells (not lymphocytes) are made in the bone marrow which is also called Chronic Granulocytic Leukemia, Chronic Myelogenous Leukemia or Chronic Myeloid Leukemia. Chronic Myeloid Leukemia is more common in adults than in children. This arises from abnormality in Blood Stem Cells resulting in proliferation of both mature and immature white blood cells as well as platelets.
Chronic Myeloid Leukemia was the first disease where the molecular abnormality leading to cancer was deciphered. A unique translocation between chromosomes 9 and 22 results in formation of a protein which stimulates the enzyme Tyrosine Kinase leading to uncontrolled proliferation of white blood cells. This abnormality was called the PHILADELPHIA CHROMOSOME. The molecular basis for this was later established as the translocation of BCR gene to the ABL gene.
Phases of Chronic Myeloid Leukemia
- Chronic phase: elevated blood counts with enlarged spleen. Patients are asymptomatic or mildly symptomatic.
- Accelerated Phase: The disease starts getting out of hand. The spleen gets bigger despite treatment. The blasts in the blood and marrow start to increase (10 to 19%).
- Blast Crisis: This is when the disease develops to a full blown leukaemia with marrow blasts more than 20%.
Risk factors: More common in males; More common in the elderly with a median age at diagnosis of 65 years; Exposure to ionising radiation; Low Immunity; Inflammatory bowel conditions; Using pesticides at work.
In most patients there are no symptoms, 25% of the patients are detected when the disease has progressed to accelerated or blast phase. Symptoms include: Frequent Infections; Weight loss; Tiredness; Swollen lymph glands; Abnormal bruising or bleeding; Abdominal discomfort; Poor appetite; Night sweats; Headaches; Bone pain.
Diagnosis: Complete Blood Count (high WBC, low Hb, high platelets); Bone Marrow Examination; Flow Cytometry; Cytogenetics; Karyotyping (establishes translocation between chromosomes 9 and 22); PCR (BCR/ABL level).
Treatment: Targeted therapy; Chemotherapy; Biologic therapy; High-dose chemotherapy with BMT.
BMT for Chronic Myeloid Leukemia
BMT was the treatment of choice for CML until TKI were developed. When is BMT needed: when patients stop responding to TKI; when CML is in Accelerated Phase or Blast Crisis.
Conditioning: High to Moderate dose of chemotherapy in younger patients. A Haploidentical (Half Matched) Donor who has Natural Killer Cell mismatch with the patient is ideal. Results: Chronic Phase 90% cured; Accelerated Phase 40-60% cured; Blast Crisis 20-40% cured.