LEUKEMIA

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LEUKEMIA

• Masatoshi Kida, M.D.
• Dept. of Pathology
• University of Vermont

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leukoproliferative disorders

• lymphoid lymphoid neoplasms acute
• chronic
• myeloid myeloid neoplasms acute
• chronic

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Lymphoid Neoplasms

• general aspects of lymphoid neoplasms
• 1. 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 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 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 Leukemia

• - generalized lymphadenopathy
• splenomegaly ALL gt AML
• hepatomegaly
• - testicular involvement ALL gt AML
• - CNS involvement ALL gt AML
• headache
• vomiting
• nerve palsie

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Acute Lymphocytic 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 lt15 y/o
• white non-white 2 1
• male gt female

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Acute Lymphocytic Leukemia/Lymphoma (ALL)
child ALL almost curable adult ALL recent
improvement in prognosis, but still with
significant mortality
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Acute Lymphocytic 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 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 peripheral
blood smear

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

peripheral B-cell
pre B-cell
pre T-cell
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ALL
clinical 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
prognostic factors

• good bad
• age 2-10 y/o lt1 y/o adult
• sex female male
• WBC gt50,000 blast/mL
• phenotype early precursor B-cell mature B-cell,
  null cell
• cytogenetics high hyperploidy pseudo-diploid
• t(922)
• 3 of pediatric ALL
• 25 of adult ALL
• t(814)

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leukoproliferative disorders

• lymphoid lymphoid neoplasms acute
• chronic
• myeloid myeloid neoplasms acute
• chronic

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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)

• most common form of leukemia in North America and
  Northern Europe
• essentially identical to small lymphocytic
  lymphoma (SLL)
• M gt F (2 1)
• elderly (gt60 y/o)
• considered incurable
• mostly asymptomatic
• hepatosplenomegaly may be present
• peripheral lymphocytosis (gt200,000)
• increased susceptibility to bacterial infection
  (most frequent cause of death)
• may associated with autoimmune hemolytic anemia

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Chronic Lymphocytic Leukemia (CLL)

• Indolent clinical course
• median survival 4-6 yrs
• occasional transformation to large non-Hodgkins
  lymphoma (Richters syndrome) --- 3 to 5

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Hairy Cell Leukemia

• uncommon variant of peripheral B-cell neoplasm
• clinically 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
clinical

• M gt 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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