Leukocytosis = increased WBC count Neutropenia = reduced neutrophills Leukemia - Hematological malignancy - Many forms - All cause excess

production of abnormal WBC - 4 groups of leukemia 1. acute myeloid leukemia (AML) 2. acute lymphoblastic leukemia (ALL) 3. Chronic myeloid leukemia (CML) 4. Chronic lymphoblastic leukemia (CLL) Epidemiology - 5% of all cancers - CLL most common - CLL occurs in 90% of patients > 50-60 years (men > women) - CML: occurs in middle aged (40-50) and can occur in young people. - Acute leukemia is rare (AML more common than ALL) - AML risk rises with age - ALL occurs mostly in childhood (3-5 years) and is most common childhood cancer Aetiology • Radiation • Exposure to chemicals and cytotoxics: - risk for patients treated with cytotoxics for other cancers (especially alkylating agents like cylcophosphamide) - radiotherapy - Paints, insecticides, benzenes • Viruses: No link but there is in animals • Genetic factors (Down’s syndrome) • Hematological disorders - Increase risk of AML by myeloprofilerative disorders, aplastic anaemia etc. Pathophysiology - Acute leukemia: accumulation of immature blood cells (functionally useless) in bone marrow and peripheral blood. - Chronic leukemia: accumulation of mature blood cells in bone marrow and tissue (variable function) - Normal haemopoesis process is altered - Cell transformation to malignancy occurs in a single cell - This occurs in pluripotent stem cell level but may occur in commited stem cell level (limited differentiation) - Accumulation of cells leads to bone marrow failure

Pluripotent stem cell Committed myeloid com. cells stem cells myeoblasts Peripheral blood lymphoid com. cells lymphoblasts

granulocytes

lymphocytes

Acute leukemia
ALL normal bone marrow replaced by malignant immature blast cells these blast cells can be from myeloid series (AML) or lymphoid (ALL) bone marrow elements are replaced with blasts and this leads to appearance of blast cells in peripheral circulation and showing pancytopenia especially in ALL: blasts can go to lymph nodes and infiltrate tissues cell lines affected are those of lymphoid cells which differentiate into T and B cells. Predominance of pre-lymphocyte cells = microlymphoblasts especially in ALL: blasts can go to lymph nodes and infiltrate tissues most common malignancy of children, rarely affects >15yrs

Classification of ALL - Classified immunologicaly based on presence of B or T cells - Common ALL: possess the common ALL antigen (cALL) - T cell and B cell types (T/ B-ALL) - Null (non-B, T and c-ALL) - C-ALL has best prognosis and B-ALL has worst prognosis AML affects myeloid cell lines depends on where in differentiation cells are mostly there are myeloblasts affecting the production of granulocytes cells it is mostly a disease of adults

Classification of AML - depends on degree of maturation and predominant differentiation - M0 = AML with no differentiation - M1-2 = granulocytic differentiation - M4 = mixed granulo and monocytic differentiation - M5 = monocytic - M6 = erythroid - M7 = megakaryocytic

SOB .examination of peripheral blood and bone marrow . joint pain. abdominal pain.presents with a short history . neutrophillic and eosinophillic leukemia - Is phase where most people with CL are diagnosed Symptoms are generalized and non-specific There is leukocytosis and <10% immature blasts in peripheral blood Accelerated phase (2nd phase): Where disease becomes worse.related to bone marrow failure . Blasts > 10% in peripheral blood Lasts < 6 weeks Blast crisis: resembles acute leukemia blasts > 30% in blood and marrow leukocyte levels double doesn’t respond to treatment and survival is short (3 months) Survival is 2-20 years Increased susceptibility to infection (immunocompromised) and autoimmune disease like haemolytic anaemia and vasculitis CLL is less responsive to therapy Clinical Symptoms Acute leukemia . Differential WBC Myelo-blasts Lymphoblasts RBC Platelets Bone marrow aspiration Cytogenic analysis Lymphadenopathy Spleen enlarged Anaemia (severe) reduced blasts Anaemia (severe) reduced blasts 100x 10^9 -250x10 ^9/L Granulocytes (esino.CNS involvement is rare but need prophylaxis as it can develop . anorexia.Pallor .Unlike acute stage: rare Haemorrhage and infections .weight loss .involvement of other organs is more common in ALL (lymph nodes) .Hypermetabolism. mostly.Patients may be Asymptomatic and disease usually diagnosed from blood tests Investigations . hemorrhage. meylo. baso and neuttrophills) Anaemia Reduced/ increased or N hypercellular Lymphocytes 10 x 10^9/L Anaemia Reduced Lymphocytes Abnormalities detected occasional common Abnormalities detected Common common Presence of Ph1 Infrequent Usual common Usual COURSE of Chronic leukemia Initial chronic phase (1st phase): last from several months – 20 years . bleeding mucus membranes and menorrhagia) . bone marrow.infection and bleeding (evident by bruising.CNS involvement cause headache. vomit and irritable behavior . bone pain.effects of infiltrating organs .MAIN physical sign is enlargement of spleen (abdominal pain) . weight loss .night sweat .malaise .skin and respiratory infections . spleen and other organs Chronic granulocytic leukemia (CGL) is most common Others include chronic Philadelphia negative CGL. purpura.Chronic leukemia • • Lymphocytic (CLL): many mature long-lived lymphocytes which accumulate in peripheral blood and cause leucocytosis Most show B-cell maturation but some show T-cell Lymphocytes go to lymphnodes and spread to liver.Hepatomegaly and spleenomegaly . unexplained worsening of fever.In all cases serum uric acid/ urate increased AML ALL CML CLL (CGL) Increased Increased Increased Increased WBC mostly.non-specific .anaemia like fatigue . fatigue. spleen which become enlarged Bone marrow is then infiltrated Cells appear normal but are unable to differentiate into plasma cells or secrete immunoglobulins Myelocytic (CML) Predominance of granulocytic cells in blood . lymphoadenopathy. hyperuricameia and bone pain Chronic leukemia . anaemia.fever. bone pain and thrombocytopenia etc. pallor.

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