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Chronic Myeloid Leukemia by Dr. Sookun Rajeev Kumar
- 1. CHRONIC MYELOID LEUKEMIA DR. SOOKUN RAJEEV K (MD) DEPT OF GENERAL MEDICINE ANNA MEDICAL COLLEGE
- 2. DEFINITION • Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line. Consequently, the peripheral blood cell profile shows an increased number of granulocytes and their immature precursors, including occasional blast cells.
- 3. This translocation results in head to tail fusion of the breakpoint cluster region (BCR) gene on chr 22q11 with ABL1 gene located on chr 9q34
- 4. CML is myeloproliferative stem cell disorder resulting in proliferation of all haematopoetic lineages but manifesting mostly in the granulocyte series
- 5. ETIOLOGY 1. Cigarette smoking accelerated the progression to blast crisis. 2. Atomic bomb survivors had increase evidence. 3. Radiotherapy for a cancer in the past. 4. Benzene
- 6. INCIDENCE • 1.5 per I00,000 population per year • Higher in men than in women • Incidence gradually increases with age until in mid 40’s when it starts to rise rapidly.
- 7. PHASES • A CHRONIC PHASE in which the disease is responsive to treatment and easily controlled. • AN ACCELERATED PHASE in which the disease control becomes more difficult. • BLAST CRISIS in which the disease transforms in to acute leukemia myeloid (70%) and lymphoblastic(30%),which is relatively refractory to treatment
- 8. CML PROGRESSES THROUGH 3 PHASES
- 9. CLINICAL PRESENTATION (SYMPTOMS) • Some patients are diagnosed while asymptomatic, during health screening tests. • Fatigue • Malaise, loss of appetite and weight loss • Symptoms resulting from splenic enlargement . • Infections , thrombosis , bleeding
- 10. CLINICAL PRESENTATION (SYMPTOMS) • Dragging abdominal pain – left upper quadrant • Abdominal fullness • Fever without chills or rigors, sweating • Gout
- 11. SIGNS • Anemia (moderate) • No Jaundice • Hepatomegaly (moderate) • Splenomegaly • Sternal tenderness present
- 12. PHYSICAL FINDINGS • Retinal haemorrhages • Purpura • Lymphadenopathy and myeloid sarcomas are unusual except in the late stages of the disease
- 13. HEMATOLOGIC FINDINGS PERIPHERAL SMEAR • Elevated white blood cell count (>1,00,000) • The circulating cells are predominantly neutrophils, metamyelocytes, myelocytes • Small portion of myeloblasts < 5% • Platelet count is elevated • Mild degree of normocytic normochromic anemia is seen
- 14. HEMATOLOGIC FINDINGS FBC • Elevated white blood cell count (>1,00,000) • The circulating cells are predominantly neutrophils, metamyelocytes, myelocytes • Small portion of myeloblasts < 5% • Platelet count is elevated • Mild degree of normocytic normochromic anemia is seen
- 17. • Marrow cellularity is increased,with an increased myeloid to erythroid ratio • Marrow blast percentage is normal or slightly elevated • Reticulin stain measured fibrosis is seen in half of the patients, collagen fibrosis is unusual BONE MARROW
- 18. • Leukocyte alkaline phosphatase is low in CML cells. • Histamine production is increased secondary to basophilia causing pruritis, diarrhea and flushing.
- 19. CHROMOSOMAL FINDINGS • Hall mark of CML is the t(9:22)(q34<q11.2) • Recognised by a presence of shortened chromosome 22(22q) designated as philadelphia chromosome. • Some patients may have complex translocations involving 3, 4, 5 chromosomes.
- 20. TREATMENT The goal of CML therapy is to achieve prolonged • non durable • non neoplastic, • non clonal haemotopoesis
- 21. TREATMENT • IMATINIB MESYLATE • HSCT • CHEMOTHERAPY • INTERFERON • LEUKAPHERISIS • SPLENECTOMY • NEWER AGENTS