LEUKEMIALEUKEMIA

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““leukoproliferative disorders”leukoproliferative disorders”

lymphoid lymphoid neoplasms acute

chronic

myeloidmyeloid neoplasms acute

chronic

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Lymphoid NeoplasmsLymphoid Neoplasms

general aspects of lymphoid neoplasms1. histologic examination is required for diagnosis

2. wide range of behavior

3. majority are of B-cell origin (80-85%)

4. disruption of normal immune regulatory mechanisms

5. deriving from a single transformed cell (monoclonal)

6. homing to and growing in the areas of origin

7. tends to spread through lymphatics and peripheral blood to distant lymphoid tissue

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Acute LeukemiaAcute Leukemia

• monoclonal proliferation of immature “blast” cells that fail to participate in the normal maturation process

• as the cells accumulate, they spill over into the peripheral blood

• morbidity and death are rarely caused by leukemic cells

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Acute LeukemiaAcute Leukemia

general overview• abrupt stormy onset• depression of marrow function

– fatigue anemia– fever, infection WBC– bleeding platelet

• bone pain and tenderness marrow expansion

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Acute LeukemiaAcute Leukemia

- generalized lymphadenopathysplenomegaly ALL > AMLhepatomegaly

- testicular involvement ALL > AML

- CNS involvement ALL > AMLheadachevomitingnerve palsie

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Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• 40% of acute leukemia• children, young adults• most frequent malignancy of childhood• 80% of childhood acute leukemia• 50% of cancer deaths in children <15 y/o• white : non-white = 2 : 1• male > female

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Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

pre B-cell

pre T-cellNull cell

80-85%

15% <5%

child ALL: almost curable

adult ALL: recent improvement in prognosis, but still with significant mortality

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Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• BM failure (pallor, lethargy, abnormal bleeding)• bone & joint pain• peripheral lymphadenopathy• splenomegaly• CNS involvement

CSF : increased pressure and cellularity

decreased glucose

normal protein

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Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• Peroxidase-granule negative ( AML)• terminal deoxynucleotidyl transferase (TdT)• common acute lymphoblastic leukemia antigen (CALLA)• T-cell antigen (T) --- mostly negative• surface Ig (sIg) --- mostly negative• cytoplasmic Ig (cIg)• PAS-pos cytoplasmic aggregate

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ALL ALL peripheral blood smearperipheral blood smear

• normocytic, normochromic anemia• thrombocytopenia• WBC may be low, normal, or high

acid phosphatase PAS ++

peripheral B-cell

pre B-cellpre T-cell www.freelivedoctor.com

ALL ALL clinical courseclinical course

• Remission in the majority of children• 5 yrs disease free period in 50% of cases• complete cures possible• significant recent improvement in survival rate for T-cell type

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ALL ALL prognostic factorsprognostic factors

good bad

age 2-10 y/o <1 y/o; adult

sex female male

WBC >50,000 blast/L

phenotype early precursor B-cell mature B-cell, null cell

cytogenetics high hyperploidy pseudo-diploid

t(9;22) 3% of pediatric ALL 25% of adult ALL

t(8;14)

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““leukoproliferative disorders”leukoproliferative disorders”

lymphoid lymphoid neoplasms acute

chronic

myeloidmyeloid neoplasms acute

chronic

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[Lymphoproliferative Disorders][Lymphoproliferative Disorders]

• clonal expansions of antigen stimulated lymphocytes• maturation arrest due to molecular derangements• primarily B cell origin• may be induced by chromosomal translocations, retrovirus,

or oncogene activation

1. chronic lymphocytic leukemia (CLL)

2. hairy cell leukemia

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Chronic Lymphocytic Leukemia (CLL)Chronic Lymphocytic Leukemia (CLL)

• most common form of leukemia in North America and Northern Europe• essentially identical to small lymphocytic lymphoma (SLL)• M > F (2 : 1)• elderly (>60 y/o)• considered incurable• mostly asymptomatic• hepatosplenomegaly may be present• peripheral lymphocytosis (>200,000)• increased susceptibility to bacterial infection (most frequent cause of

death)• may associated with autoimmune hemolytic anemia

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Chronic Lymphocytic Leukemia (CLL)Chronic Lymphocytic Leukemia (CLL)

• Indolent clinical course• median survival : 4-6 yrs• occasional transformation to large non-Hodgkin’s lymphoma (Richter’s

syndrome) --- 3 to 5 %

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Hairy Cell LeukemiaHairy Cell Leukemia

uncommon variant of peripheral B-cell neoplasmclinically middle age to elderly (younger than CLL)

splenic red pulp involvement

histologically lymphocyte with finger-like projections

phenotypically TRAP (Tartrate Resistant Acid Phosphatase)

CD19, CD20

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Hairy Cell Leukemia Hairy Cell Leukemia clinicalclinical

• M > F (3-5 : 1)• splenic red pulp involvement red pulp “lake”• tends to follow an indolent course

• pancytopenia - most prominent feature

- granulocytopenia recurrent bacterial infection

- anemia fatigue

- thrombocytopenia bleeding• good response to some chemotherapy regimen

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