Leukemia

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Leukemia

• DR. SHAHID MAHMOOD

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Leukemia

• Is a malignant hematological disorder
  characterized by a proliferation of abnormal
  white cells that infiltrate the bone marrow,
  peripheral blood and organs
• 4 main types of leukemia
• Acute or chronic
• Myelogenous or Lymphocytic

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FAB CLASSIFICATION

• M0 minimally differentiated
• M1 myeloblastic leukemia without maturation
• M2 myeloblastic leukemia with maturation
• M3 hypergranular promyelocytic leukemia
• M4 myelomonocytic leukemiaM4Eo variant,
  increase in marrow eosinophils
• M5 monocytic leukemia
• M6 erythroleukemia (DiGuglielmo's disease)
• M7 megakaryoblastic leukemia

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Types of Leukemia

• Acute Leukemia
• progresses quickly
• characterized by the proliferation of
  undifferentiated cells in the bone marrow
• Chronic Leukemia
• slower progression
• uncontrolled expansion of mature cells

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Types of Leukemia

• Acute and chronic leukemias are further
  subdivided into
• Myelogenous Leukemias
• those that are from hemopoietic stem cells
• Lymphocytic Leukemias
• arise from any other cells in the bone marrow

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Four main subtypes of leukemia

• The four subtypes account for 50 of all leukemia
  in the U.S
• 1. ALL Acute Lymphocytic Leukemia
• 2. AML Acute Myelogenous Leukemia
• is referred to as ANLL- acute nonlymphocytic
  leukemia
• 3. CLL Chronic Lymphocytic Leukemia
• 4. CML Chronic Myelogenous Leukemia

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Hemopoiesis and Lymphopoiesis

• Pluripotent Stem Cells
• Most primitive cells
• Mature blood cells and lymphocytes develop from
  pluripotent cells
• The pluripotent stem cells differentiate into
  either
• myeloid stem cells or lymphoid stem cells
• The myeloid stem cells produce progenitors
• Progenitors lead to the production of mature
  functional cells

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Leukemia Development

• The development of Leukemia
• uncontrolled and accelerated production of
  progenitors which results in incomplete or
  defective cell maturation
• Acute leukemia- rapid proliferation of primitive,
  undifferentiated stem cells
• Chronic leukemia- differentiated defective cells

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Leukemia Symptoms

• Symptoms result from interference with normal
  processes
• The leukemic cells accumulate in the bone marrow
• Hampers the production of normal blood cells
• Results in decreased counts
• Whats this called?

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Symptoms

• Anemia, thrombocytopenia, neutropenia
• fatigue
• pallor
• bleeding
• infection

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ALL-Acute Lymphocytic Leukemia-Epidemiology

• 5/100,000 people affected
• ALL is the most common pediatric cancer
• 80 of children with acute leukemia have ALL
• ALL most commonly a childhood disease
• Peak incidence between ages 2 and 6 yr old
• More common in males, whites compared to blacks,
  and Jews compared to non-Jews

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ALL-Acute Lymphocytic Leukemia-Etiology

• Unknown causes
• Thought to be associated with ionizing
  radiation-atomic bomb survivors 10-15 increase
  incidence
• hydrocarbons, benzene, alkylating agents such as
  cyclophosphamide
• Heredity
• identical twin has 20 likeliness
• Down syndrome- 15-20 increased risk
• Naturally occurring retroviruses and the human
  T-cell lymphotropic virus
• -adult ALL- not childhood ALL

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ALL- Acute Lymphocytic Leukemia Prognosis

• Complete remission more then 75, duration and
  therefore cure are related to a number of
  factors
• age ALL in children lt 2 and gt 10 poor prognosis.
  lt 1 yr old worst prognosis
• Adult ALL worse, gt 50 yrs old very poor prognosis
• WBC (leukocyte)- initial WBC count 0f lt
  10,000/mm3 is more favorable than a count of
  20,000 to 49,000 and a count gt 50,000/mm3 is
  least favorable

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ALL- Acute Lymphocytic Leukemia

• Clinical presentation
• suppressed blood counts - anemia,
  thrombocytopenia, neutropenia and associated
  symptoms
• flulike malaise with fatigue and pallor from
  anemia
• Thrombocytopenia- bleeding gums, epistaxis ,
  petechiae (tiny red spots on the skin caused by
  escaped blood), ecchymoses (discolored skin due
  to blood in tissues), menorrhagia, excessive
  bleeding after dental procedures

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ALL- Acute Lymphocytic Leukemia

• Clinical presentation
• Neutropenia causes increased risk of infections,
  respiratory, dental, sinus, perirectal, and UTI
• Other common symptoms
• liver, splenic, and testicular enlargement
• may mimic rheumatoid arthritis with swollen
  joints, bone pain, and tenderness causing a child
  to limp or not walk
• Central nervous symptoms-vomiting, headaches,
  papilloedema (optic disc swelling) neck
  stiffness, and cranial nerve palsy
• ALL- symptoms rarely occur more than 6 weeks
  before diagnosis

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ALL-Acute Lymphocytic Leukemia

• Detection/Diagnosis
• Blood count
• thrombocytopenia and anemia occur 2/3 cases at
  diagnosis
• WBC vary
• Abnormal increase in WBC poor prognosis
• Immunophenotyping
• morphological evaluation, special stains,
  electron microscopy, and surface markers
• Establish diagnosis 90 of cases

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ALL-Acute Lymphocytic Leukemia

• Detection/Diagnosis
• A bone marrow biopsy is done to make a definitive
  diagnosis
• The amount of leukemic blast cells is determined
  lt25 is positive for leukemia
• Other abnormalities
• hyperuricemia, hypomagnesemia, hypocalcemia, and
  hypercalcemia
• 30 of pts have low serum levels of
  immunoglobulins (proteins that can act as
  antibodies)

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ALL-Acute Lymphocytic Leukemia,Detection/Diagnosis

• Liver, periosteum, bone may have leukemic
  infiltrates
• Mediastinal mass may be present- high risk pt.
• Two most common sites for extramedullary leukemia
  are
• CNS
• Testes

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ALL-Acute Lymphocytic Leukemia

• Pathology
• ALL is characterized by the uncontrolled
  proliferation of lymphoblasts
• The overproduction of lymphoblasts limits the
  production of other cells by overcrowding and
  inhibits cell growth and differentiation
• Staging/classification
• based on French-American-British (FAB) system.
  Classified according to cell size, nuclear shape,
  number of nuclei, prominence of nuclei, and
  amount of cytoplasm
• Levels L1-L3
• 3 being the worse prognosis. Majority of
  pediatric are L1.

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ALL-Acute Lymphocytic Leukemia

• Staging/classification
• 25 of patients with ALL are categorized by
  T-cell, B-cell, or pre B-cell markers
• 70 are classified with null-cell type
• this null-cell type reacts to antibody made from
  an antigen found in ALL cells
• antigen is called CALLA, or common
  leukemia-associated antigen

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ALL-Acute Lymphocytic Leukemia

• Treatment Techniques
• Used alone or in combination-
• Radiation Therapy (RT)- various techniques
• TBI- in prep for BMT
• Brain, testes, or CNS (CSI) may be tx with more
  radiation depending on involvement
• TBI- 12Gy, 2 Gy/fx BID 3 days
• CNS- helmet (brain) 18 Gy, 2Gy/day, 9 days
• CSI- Brain and spine (tx csf) brain- 24Gy, spine
  15 Gy
• Testes- 4 Gy , 1 tx- often used w/TBI

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ALL-Acute Lymphocytic Leukemia

• Treatment Techniques-cont
• Chemo- 3 stages of drugs induction,
  consolidation, and maintenance. Protocols change
  and vary by institutions.
• Bone Marrow Transplant-no longer experimental for
  certain diagnosis and is tx of choice for ALL,
  AML, and CML

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ALL-Acute Lymphocytic Leukemia

• Side Effects
• Acute and Temporary
• TBI
• GI-nausea, vomiting, diarrhea, anorexia, malaise
• Mucosa of mouth, pharynx, bladder and rectum may
  be affected
• Skin reactions, alopecia, interstitial
  pneumonitis
• Decreases blood counts

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ALL-Acute Lymphocytic Leukemia

• Side Effects
• Chronic
• permanent sterility
• cataracts
• hepatic fibrosis and radionecrosis of genital
  tissue, muscle, and kidney
• secondary malignancy
• lung problems
• heart problems
• retarded growth

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AML-Acute Myelogenous Leukemia

• Epidemiology
• incidence is 5 times greater than ALL
• Occurs equally at all ages, slightly more common
  gt50
• 80 of adult leukemia is AML
• slightly more common in males
• Etiology
• Same as for ALL- prior exposure to radiation,
  benzene, alkylating agents, Fanconis anemia,
  Bloom syndrome (genetic chromosome disorders)

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AML-Acute Myelogenous Leukemia

• Prognosis
• prognostic indicators similar to ALL
• unfavorable prognosis if
• gt 50 yr.s old
• Myelodysplastic syndrome- dx of elderly,
  preleukemia, stem cell disorder
• poor performance status
• low serum albumin

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AML-Acute Myelogenous Leukemia

• Prognosis
• Children w/AML have poorer prognosis than w/ALL
• WBC lt 20,000, mm is more favorable the 20-49,000
  mm, gt 50 worst prognosis
• Age, tumor burden at time of diagnosis, drug
  sensitivity of cells are more important
  prognostic indicators than cell morphology

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AML-Acute Myelogenous Leukemia

• Clinical Presentation
• abrupt onset (1-6 month prodromal period)
• Similar symptoms to ALL-fatigue, flulike,
  bleeding, petechiae, purpura (hemorrhage under
  skin), epistaxis, gingival bleeding, GI bleeding,
  urinary tract bleeding due to decreased platelets
• increased susceptibility to infections due to
  neutropenia
• Enlarged spleen may be felt

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AML-Acute Myelogenous Leukemia

• Detection and Diagnosis
• blood counts, abnormal blood counts lead to the
  detection of AML
• Thrombocytopenia, anemia, increased leukocytes
• chromosomal abnormalities-30-50 of AML pt
• Presence of Auer rods (structures found in
  myeloblasts, myelocytes, and monoblasts)
• bone marrow aspiration biopsy for a definitive
  diagnosis

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AML-Acute Myelogenous Leukemia

• Detection and Diagnosis
• if 30 blast cells are present, acute leukemia is
  confirmed
• a differential diagnosis is made from a staining
  procedure
• Immunophenotyping as in ALL establishes diagnosis
  in 90 of cases

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AML-Acute Myelogenous Leukemia

• Pathology
• proliferation of precursor cells that have lost
  the ability to differentiate
• It involves the hemopoietic stem cells or
  pluripotent cells
• results in the gradual accumulation of
  undifferentiated cells in marrow or other organs

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AML-Acute Myelogenous Leukemia

• Staging and Classification
• FAB system is used for morphological evaluation
• Maturation states are categorized from M0
  (undifferentiated) to M7 (megakaryocyte)

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AML-Acute Myelogenous Leukemia

• Treatment techniques
• a combination of chemo, radiation therapy, and
  bone marrow transplant
• Side effects-same as ALL

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CLL-Chronic Lymphocytic Leukemia

• CLL most common leukemia
• it accounts for 30 of leukemias
• CLL is 2 X as common as CML
• incidence increases with age, 65 avg, rare in
  people under 35
• males more common- 2X compared to women
• equal blacks/whites

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CLL-Chronic Lymphocytic Leukemia

• Etiology
• heredity- 3x increased risk if 1st relative has
  CLL
• Most notable familial clustering of all leukemias
• Immunodeficiency syndromes and viruses
• no conclusive link with radiation exposure or
  retroviruses
• Prognostic Indicators
• stage at time of diagnosis
• age
• doubling time of peripheral blood lymphocyte
  count
• pattern of bone marrow involvement
• T-cell variety poorer prognosis

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CLL-Chronic Lymphocytic Leukemia

• Clinical presentation
• incidental findings on blood tests
• lymphocyte counts gt 10,000/ mm
• often asymptomatic
• night sweats, fatigue, fever, weight loss
• Lymphadenopathy(?) may be present, spleen almost
  always enlarged
• uncomfortable neck masses are common at later
  stages

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CLL-Chronic Lymphocytic Leukemia

• Detection/Diagnosis
• blood tests
• Pts always exhibit lymphocytosis
• anemia, thrombocytopenia
• B-cell origin in 95 of CLL cases
• enlarged LN
• enlarged spleen
• 50 of pt have chromosome abnormalities

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CLL-Chronic Lymphocytic Leukemia

• Pathology
• origin may be bone marrow lymphoid tissue
• increased number of leukemic cells in bone
  marrow, blood, lymph nodes, spleen resulting in
  enlarged spleen, and decreased bone marrow
  function

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CLL-Chronic Lymphocytic Leukemia

• Staging/Classification
• Rais staging system (one system)
• Three major prognostic indicators are
• Stage 0- low risk
• Stages I and II- Intermediate risk
• Stages III and IV- high risk
• Stages are based on presence of adenopathy,
  splenomegaly, anemia, and thrombocytopenia. The
  majority of patients are in the intermediate risk
  group

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CLL-Chronic Lymphocytic Leukemia

• Staging/Classification
• The Binet is another staging system that is based
  on involvement of cervical nodes, axillary nodes,
  inguinal nodes, spleen, and liver
• CLL- subtypes
• Classified as B-cell or T-cell

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CLL-Chronic Lymphocytic Leukemia

• Treatment Techniques
• no optimal treatment
• early stage pt- no tx benefit
• chemo used to treat anemia, thrombocytopenia
• radiation used to treat palliatively for
  localized tumors of lymph tissue
• surgery used to remove spleen because of
  cytopenia, cells accumulate in the spleen

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CML-Chronic Myelogenous Leukemia

• CML accounts for 20-30 of all leukemias
• rare in children
• uncommon before age 21
• peaks mid 40s
• males slightly more common

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CML-Chronic Myelogenous Leukemia

• Etiology-unknown
• linked to radiation, benzene
• Philadelphia chromosome is present in 95 of CML
  patients
• Abnormal Chromosome 22- loss of part of long arm
• Prognostic Indicators dependent on
• spleen size, platelet count, hematocrit ( of
  erythrocytes in blood volume), gender, of blood
  myeloblasts (immature BM cell)
• Can turn into an acute leukemia after 3 yrs-blast
  crisis
• Active phase- 2yr survival

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CML-Chronic Myelogenous Leukemia

• Clinical presentation
• three stages
• chronic, accelerated, and acute phase (blast
  crisis)
• Early phase- sx are insidious, mild and
  nonspecific malaise , fatigue, sweating,
  intolerance to heat, easy bruising
• Splenic enlargement- vague discomfort in LUQ,
  early satiety, wt loss, peripheral leg edema
• Blast crisis 3-4 yrs, all organs are invaded by
  the leukemic blast cells
• symptoms include fever, bone pain, weight loss

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CML-Chronic Myelogenous Leukemia

• Active disease
• Wt. loss gt 10 in lt 6 months
• Fever
• Extreme fatigue
• Anemia
• Thrombocytopenia
• Organ involvement (other than LN, spleen, liver,
  bone marrow)
• Progressive or painful enlargement of spleen

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CML-Chronic Myelogenous Leukemia

• Detection Diagnosis
• Difficult, insidious, found by accident
• Indicators- mild to moderate anemia, leukocytosis
• myeloblasts, promyelocytes, and nucleated red
  blood cells- are present in blood
• Absence of LAP score (leukocyte alkaline
  phosphotase)
• BM specimen shows granulocytic and megakaryocytic
  hyperplasia
• Most importantpresence of Philadelphia
  chromosome

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CML-Chronic Myelogenous Leukemia

• Pathology
• Abnormal hemopoietic stem cells that give rise to
  cells that have Philadelphia chromosome
• Staging/Classification
• Three distinct stages, chronic (stable),
  accelerated phase, and acute phase (blast crisis)

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CML-Chronic Myelogenous Leukemia

• Treatment Techniques
• Radiation
• TBI and spleen
• Chemo
• BMT

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Role of Radiation Therapist

• Radiation departments who do not treat BMT
  patients or have pediatric oncology services may
  not see many leukemia patients
• Education
• Patience- few trips to gain trust
• Extra time, preparation (ANESTHESIA)

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Role of Radiation Therapist

• Radiation departments who do not treat BMT
  patients or have pediatric oncology services may
  not see many leukemia patients
• Education
• Patience- few trips to gain trust
• Extra time, preparation (ANESTHESIA)

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Leukemia

• THANKYOU FOR BEING WITH ME