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Dr . Mohamed Awad Lect.

Medical Oncology CMU MD, NCI, Cairo University

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• Accumulation of CLL cells in BM, PB and lymphatic organs. • Progressive BM insufficiency with anemia and thrombocytopenia. • Neutropenia and secondary immune deficiency leads to infection. • AIHA (20%)

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• Lymphocytosis in routine investigations. • In > 50% of patients: localized lymphadenopathy • • • • (mostly cervical). -FUO. -Night sweats. -Wt loss. • B-symptoms:

• Recurrent infections: e.g. Herpes zoster.

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• AIHA or immune thrombocytopenia. • Later stages:

– – – –

Marked lymphadenopathy Splenomegaly Hepatomegaly Failure of normal hematopoiesis

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• Rai Classification for CLL
– 0 - lymphocytosis (>5 G/L) 10 – I - lymphocytosis + lymphadenopathy  8 – II - lymphocytosis + splenomegaly +/lymphadenopathy  6 – III - lymphocytosis + anemia (Hb <11g%) +/lymphadenopathy or splenomegaly  2y – IV - lymphocytosis + thrombocytophenia (Plt <100G/L) +/- anemia +/-lymphadenopathy +/splenomegaly

• Binet Classification for CLL
– A. < 3 involved areas, Hb > 10g%, Plt > 100G/L  10y – B. > 3 involved areas, Hb > 10g%, Plt > 100G/L  7y – C. - any number of involved areas, Hb < 10g%, Plt < 100G/L  2y

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• Chlorambucil • Combinations such as CVP and CHOP • Purine Analogues (i.e., fludarabine) • Single-Agent Antibodies e.g. anti-CD20) • Stem cell transplantation.

• Incidence = 1-2 per 100,000 • Incidence increases with age • Median age range at presentation: 45 to 55 years

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• 20% to 40% of patients asymptomatic, • When symptoms occur they usually relate to
– Splenomegaly (left upper quadrant discomfort or early satiety), – Increased white cell production (bone pain, mild fever, night sweats, weight loss), – Anemia (dyspnea, fatigue, pallor).

• Dramatic hypermetabolism (night sweats, heat intolerance, weight loss) • Acute gouty arthritis related in part to hyperuricemia; • Priapism, tinnitus, or stupor • Left upper quadrant and left shoulder pain as a consequence of splenic infarction and perisplenitis;

Clinical Course: Phases of CML
Advanced phases Chronic phase Accelerated phase Blast crisis

Median 5–6 years stabilization

Median duration 6–9 months

Median survival 3–6 months

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• Leukocyosis , mature neutrophils, or granulocytes, have decreased apoptosis • Early myeloid cells such as myeloblasts, myelocytes, metamyelocytes, and nucleated red blood cells are present in the blood smear A mild-to-moderate anemia may be present at diagnosis and is usually normochromic and normocytic Thrombocytosis is common at diagnosis.

Blood film at 400X magnification demonstrates leukocytosis with the presence of precursor cells of the myeloid lineage. In addition, basophilia, eosinophilia, can be seen.

Ph chromosome

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Cytogenetic Abnormality of CML: The Ph Chromosome

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• To 1953: -No Treatment • 1964: • 1970: • • 1990: • 2000: - Busulfan. - Hydroxyurea -BM Transplantation - Interferon-α. - Imatinib

Mechanism of Action of Imatinib

Goldman JM, Melo JV. N Engl J Med. 344:1084-1086.

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