Chapter 27
Leukemia
Leukemia: a heterogeneous group of neoplastic diseases of the hemopoetic system.
 Categorized:
o Based on the natural history:
 Acute: progresses quickly and is characterized by proliferation of undifferentiated
cells in the bone marrow; involves the rapid proliferation of primitive,
undifferentiated stem cells. The accumulating leukemic cells are immature or have
undergone a defect in maturation.
 Chronic: distinguished by a slower progression of disease and the uncontrolled
expansion and accumulation of mature cells; cellular differentiation (maturation) is
largely preserved.
o Based on dominant cell line:
 Myelogenous: those arising directly or indirectly from hemopoietic stem cells
 Lymphocytic: those arising from other cells populating the bone marrow
 ALL: characterized by the invasion of the bone marrow by leukemic lymphoblasts
 AML: results from the proliferation of defective or incompletely matured cells derived from
the pluripotent hemopoeitic stem cells
 CLL: disorder of morphologically mature, but immunologically less mature, lymphocytes.
An increased proliferation results in an enormous accumulation of these cells in the marrow,
blood, lymph nodes, liver, and spleen causing an enlargement of the organs and a decrease in
bone marrow function.
 CML: involves the replacement of marrow cells with mature myeloid cells that are
insensitive to the normal proliferation control mechanisms.
Anatomy:
 Leukemia develops during the formation of the constituent elements of the blood and
lymphocytes; the production of the hemopoietic or lymphopoietic progenitors is uncontrolled
and greatly accelerated, resulting in incomplete or defective cellular maturation.
 Pluripotent stem cells have a self-renewing capability and generate differentiated cells of
multiple lineages:
o Myeloid stem cells provides the progenitors for the six types of blood cells
 The hemopoietic process through which mature erythrocytes, neutrophils,
eosinophils, basophils, monocytes, and platelets are formed.
o Lymphoid stem cells provide the progenitors for the classes of lymphocytes.
 The lymphopoietic process through which lymphocytes are formed.


Symptoms result from the leukemic cells interference with normal processes.
Leukemic cells accumulate in the bone marrow, impairing the body’s normal production of
adequate supplies of :
o RBCs: anemiafatigue, pallor
o WBCs: neutropeniainfection
o Platelets: thrombocytopeniableeding
ACUTE LYMPHOCYTIC LUEKEMIA:
Epidemiology:
 ALL is the most common of the pediatric malignancies
 Approximately 80% of children with acute leukemia have the ALL subtype.
 Between 2-10 yrs; uncommon in persons over the age of 14
 Higher among males, whites, and Jewish
Etiology:
 Cause unknown
 Higher incidence in survivors of the atomic bomb explosions in Japan has suggested that
ionizing radiation may play a role.
 Benzene derivatives and other hydrocarbons and alkylating agents
 Heredity: if one identical twin diagnosed, other twin has 20% risk within 6 months
 Down syndrome: 10 to 30 fold increase
 HTLV
Prognostic indicators:
 More than 75% of patients can be expected to experience a complete remission: duration
and subsequent potential for cure appear to be related to age, white blood count at the
time of the diagnosis:
o Less than 10,000/mm3 is more favorable
o 20,000/mm3 – 49,000/mm3 medium
o Greater than 50,000/mm3 least favorable.
 Younger than 2, older than 10- poor prognosis
 CNS involvement, mediastinal mass, massive organomegaly and/or adenopathy and
abnormal DNA content also carry poor prognosis.
Clinical Presentation:
Depends on the cells suppressed (increased proliferation of white cells crowds out production of
other cells)
 Anemia: flu-like malaise, fatigue, pallor
 Thrombocytopenia: bleeding gums, epistaxis (Nosebleeds), petechiae (tiny red spots on
the skin caused by the escape of small amounts of blood- pinpoint hemorrhage),
ecchymoses (discoloration of the skin caused by the escape of blood into tissues),
menorrhagia (excessive menstrual bleeding), and excessive bleeding after dental
procedures.
 Neutropenia: increased susceptibility to respiratory, dental, sinus, perirectal, and urinary
tract infections.
Other:
 Liver, splenic, and testicular enlargement
 Mimic rheumatoid arthritis with joint swelling, bone pain, and tenderness
 Rarely occur more than 6 weeks before diagnosis
 Vomiting, headaches, papilledema (swelling of the optic disc), neck stiffness, and cranial
nerve palsy are indicative of CNS involvement.
Detection & Diagnosis
 Blood cell count
 Thrombocytopenia and anemia occur in most patients (2/3)
 WBC: can be low or high- abnormal increase indicate poor prognosis
 Bone marrow aspiration: the amount of leukemic blast cells is the determinant for a
definitive diagnosis- if greater than 25%- positive for leukemia

Other abnormalities present: hyperkalemia, hypomagnesemia, hypocalcemia, and
hypercalcemia, 30% have low serum levels of immunoglobulins, leukemic infiltrates of
the liver, periosteum, and bone; mediastinal mass in high risk patients; extramedullary
leukemia ate the CNS and testes (sanctuary sites, because they are hidden from most
chemotherapy agents).
Pathology:
 ALL is characterized by an unregulated proliferation of lymphoblasts; the disease cells limit
the production of other healthy cells by overcrowding and inhibiting cell growth and
differentiation.
Treatment: used alone or in combination
 Radiation therapy
 TBI: used to immunosuppress the patient in combination with a bone marrow transplant.
 Dose:
 Totaling 1200 cGy (200 cGy bid for 3 consecutive days)
 Low dose rate (10 cGy/min) to spare late-responding tissues such as abdominal
organs and lungs.
 Field design:
 40 X 40 – largest jaw size that can be set on the treatment unit
 Gantry placed in the lateral position; SSD of 5 ft or more needed
 Patient sits in box with knees toward the chest, arms by the side with forearms on
the side of the knees to act as compensators for the lungs,
 Patient’s eyes and face should be looking straight ahead
 Treated from the right and left lateral positions
 Thermoluminescent dosimeters (TLDs) are placed between the patient’s ankles,
knees, and thighs once during a treatment to check midline doses,
 To even the dose over the uneven surfaces of the body compensators are
positioned over the thinnest body parts, such as the head and neck area, and the
foot and ankle areas.
 Side Effects
 Acute- subside in time
 GI: NVD, anorexia, malaise
 Mucosa of the mouth, pharynx, bladder, and rectum
 Skin: itching, tingling, bruising, dry and inelastic skin that cracks easily,
erythema
 Alopecia
 Interstitial pneumonitis
 Chronic
 Permanent sterility
 Cataracts
 Hepatic fibrosis
 Necrosis of the genital tissue, muscle, and kidneys
 Helmet: used to encompass the meninges; prophylactic
 Dose:
 200 cGy for nine consecutive days for a total of 1800 cGy
 Field design:
 Parallel opposed lateral fields
 Field size should cover the meninges and C2, with fall off around the head
 Lenses of the eyes and mouth should be blocked with an adjustable block
 Side Effects: see CNS technique Side Effects
 CNS technique: combination of a helmet and posterior spine field used to treat positive
cells in the cerebral spinal fluid
**Gap calculation must be done:
 For the match of the helmet and spine field
 Spine fields: match at the level of the spine to ensure coverage of the entire CNS
with no cold spots
**Feathering technique: junctions are shifted by changing the lengths of all fields- done
daily with three different match lines
**Critical structures:
 Lenses of the eyes: blocked with a moveable clinical block
 Spinal cord: 1500 cGy
o Helmet:
 Dose:
 Treated to a total dose of 2400 cGy, 150 cGy each day for 16 days
 Field design:
 Two lateral parallel opposed ports
o Spine:
 Dose:
 150 cGy for 10 days for a total of 1500 cGy
 Field design:
 May be treated in two parts to cover spine through S2- line of divergence
determines collimator angle for helmet field
 Depends on the contour of the patient
**Side Effects:
 Acute
o Skin reactions and hair loss
o Low blood counts
o N&V
o Malaise
o L’hermittes: if spine treated- sensation of an electric shock in the arms, legs,
or neck when the neck is flexed.
 Chronic
o Neuropsychologic and intellectual deficits
o Cataracts
o Growth retardation
o Hypothalamic pituitary dysfunction: an abnormality in the hormonal
secretions that include growth hormones, thyroid hormones, adrenal hormones
and sex related hormones
o Myelopathy: overdose to the spine- irreversible
o Secondary tumors- benign or malignant
 Testes: (sanctuary site, because they are hidden from most chemotherapy agents),
usually in combination with total body irradiation
 Dose:
 400 cGy for a single electron fraction,
 Field design:
 Patient lies supine in a lithotomy position
 Field is set up to encompass the entire organ

Chemotherapy: divided into four groups
 Induction: given immediately after the diagnosis to eradicate all detectable leukemia
 Prednisone
 Dexamethasone
 Vincristine
 L-asparaginase
 Consolidation: begins after remission has been achieved
 High dose intravenous methotrexate
 Etoposide
 L-asparaginase
 Prophylaxis of overt CNS disease
 Methotrexate
 Maintenance
 Intravenous mercaptopurine
 Systemic methotrexate

Bone marrow transplantation
o Treatment of choice for ALL, AML, and CML
o Procedure:
 Suitable donor
 Identical twin
 Autologous transplants
o The reinfusion of a patients own marrow that has been harvested and
cryopreserved while the patient was in remission
o Leukemic cells are removed from the marrow using monoclonal antibodies
directed against cell surface antigens that are expressed on leukemic blasts but
not on normal stem cells.
 Allogenic transplants
o Use human leukocyte antigen (HLA) histocompatable siblings from bone
marrow registries; available to 20% to 30% of patients

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Harvest healthy marrow
 Risks are small- primarily related to anesthesia
 Done in the operating room under sterile conditions
 Multiple aspirations are drawn from the donors anterior and posterior iliac crests
Marrow is then infused into a patient whose diseased marrow has been destroyed or
ablated by chemotherapy or TBI- to reduce the leukemic cell load and impair the
host’s ability to reject the donor marrow
Transplanted marrow finds its way into bone marrow cavities and begins supplying
the patient with normal, healthy hemopoietic cells within 2 to 4 weeks
BMT Failure:
 Recurrent leukemia (primarily in autologous donors)
 Graft verses host disease (occurs in 50%) may exist as a slight skin rash or may progress
to a life threatening syndrome
ACUTE MYELOGENOUS LEUKEMIA
Epidemiology:
 Patients over 40 with a median age of 65
 Approximately 90% of adults with acute leukemia have AML
 Higher among white males
Etiology:
 Similar to ALL
 Ionizing radiation , benzene and alkylating agents
Prognostic indicators:
 Similar to ALL
 Older than 50, poor health,, impaired organ function
 Children with AML have poorer prognosis than ALL
 WBC less than 20,000/mm3 more favorable
 More than 50,000/mm3 least favorable
 Depends on age, subtype of cells, whether recurrent or not.
Clinical presentation:
 Onset may be abrupt, but most patients experience a 1-6 month prodromal period
 Nonspecific flu-like symptoms, anemia (fatigue, pallor, dyspnea)
 Thrombocytopenia (petechiae, purpura (hemorrhage under the skin), epistaxis, gingival
bleeding, GI or urinary tract bleeding)
 Neutropenia (susceptibility to local infections such as skin abscesses, systemic infections
with fever, chills, and site specific symptoms
 Sensation of an enlarged spleen
Detection & Diagnosis:
 CBCs with differential leukocyte and platelet counts
 Chromosomal abnormalities occur in 30% to 50% of patients
 Circulation of Auer rods in leukemic cells (structures present in the cytoplasm of
myeloblasts, myelocytes, and monoblasts) essential for diagnosis
 Bone marrow biopsy- hypercellular- more than 30% blast cells present, and decrease in
normal precursors
Pathology:
 Unregulated proliferation of early precursor cells that have lost the ability to differentiate in
response to hormonal signals and cellular interactions, involves the hemopoietic stem cells or
pluripotent cells, result is a gradual accumulation of undifferentiated cells in marrow or other
organs, cells do not reach maturity or are defective at maturity.
Treatment:
 Radiation: same as ALL
 Chemotherapy
o Remission induction
 Cytosine arabinmoside: mimics the natural building blocks of RNA and DNA to
prevent the cell from growing
 Anthracycline antibiotic (duanorubicin, doxorubicin, or idarunicin): impede cell
survival by interacting directly with the nuclear DNA
o Post induction consolidation/maintenance:
 Cytosine arabinmoside
CHRONIC LYMPHOCYTIC LEUKEMIA
Epidemiology:
 Increases with age 71 average age of onset
 Rare in persons younger than 40
 Twice as many males than females, less incidence in Japanese and Asians, equal
incidence in blacks and whites.
Etilology:
 Heredity- first degree relatives of persons with CLL have a 2-7 fold increase in risk
 Immunodeficiency syndromes and viruses
 Chemicals used in the rubber industry
 Only leukemia not association with radiation exposure
Prognostic indicators:
 The stage at the time of diagnosis, age, doubling time of the peripheral blood lymphocyte
count, and pattern of bone marrow involvement.
Clinical presentation:
 Minimal changes in blood count
 Often occurs as incidental finding on blood tests taken during routine medical visits
(WBC higher than 10,000/mm3)
 Fatigue, fever, night sweats, weight loss
 Lymphadenopathy and enlarged spleen common
Detection:
 Blood tests (lymphocytosis, anemia and thrombocytopenia)
 Enlargement of lymph nodes and spleen
 50% have chromosomal abnormalities.
Pathology:
 Origin may be in the bone marrow lymphoid tissue
 Increased proliferation of leukemic cells in the bone marrow, blood, lymph nodes, and
spleen, with resulting organ enlargement and decreased bone marrow function.
Treatment:
**Optimal treatment is unknown
**Those with early stage disease may not benefit from treatment
 Chemotherapy: for progressive anemia and thrombocytopenia
o Chlorambucil: prevents the separation of the strands of DNA which is necessary for
cell replication
o Prednisone
 Radiation therapy: (palliation) used for localized masses of lymphoid tissue and/or to
reduce size of enlarged spleen.
o Dose:
 100 cGy per day for 5 days for total 500 cGy
o field design:
 AP/PA
 Must encompass the entire spleen with a 1 cm margin around
 Setups done through palpation or fluoroscopy
 Simulation necessary to localize spleen and ensure kidney is out of field.
 Surgery: removal of spleen
CHRONIC MYELOGENOUS LEUKEMIA
Epidemiology
 Accounts for approximately 15% of all leukemias
 Rare in childhood and uncommon before the age of 20
 Peaks in mid 40s
 Slight male increased incidence
Etiology
 Cause unknown
 Radiation and benzene
 Philadelphia chromosome
Prognostic indicators:
 Spleen size, platelet count, hematocrit, gender, and percentage of blood myeloblasts
 Typically transforms into an acute leukemia age a chronic phase of about 4 to 6 years,
when the patient enters a blast crisis
 Active phase of disease has a median survival time of approximately 2 years
Clinical presentation:
**Divided into three stages:
 Chronic
o Usually insidious, symptoms mild and nonspecific
o Malaise, fatigue, heat intolerance, sweating, and easy bruising
o Splenic enlargement in 90% of cases- discomfort in LUQ, early satiety, weight loss,
and peripheral leg edema
 Acute phase (blast crisis)
o Within 3 to 4 years
o All the organs of the body are invaded by leukemic blast cells, and the circulating
blood count can reach several hundreds of thousands per mm3
o Fever, bone pain more pronounced weight loss
 Accelerated
o Weight loss greaten than 10% in 6 months, fever, extreme fatigue, anemia,
thrombocytopenia, organ involvement (other than lymph nodes, spleen, bone marrow
and liver
o Progressive or painful enlargement of the spleen.
Detection and Diagnosis:
 Difficult- insidious and generally not detected, usually found accidentally.
 Mild to moderate anemia and leukocytosis
 Myeloblasts, promyelocytes and nucleated red cells present in the blood
 Most important diagnostic factor is the presence of the Philadelphia chromosome
Pathology:
 Abnormal hemopoietic stem cells that give rise to progeny that have the Philadelphia
chromosome
 Because of the abnormal stem cells and increased proliferation of granulocytic and
megakaryocytic cells exists
 Erythropoiesis is impaired
Treatment:
 Radiation therapy:
o Spleen and TBI
 Chemotherapy:
o Alpha- interferon: an immunotherapeutic drug
o Busulfan: alkylating agent- causes gradual reduction of the leukocyte count toward
normal, an increase in the RBC count and a decrease in the spleen size
o Hydroxyurea: blocks DNA synthesis by inhibiting a ribonucleotide reductase
 Bone marrow transplant:
o Allogeneic bone marrow transplantation is the only curative treatment, but only 20%
to 30% will find match
o Success rate is lower in the accelerated phase
Outcomes:
 ALL: only 4% survival rate before 1962; now 75-80% 5 year survival
 AML: 60-70% remission rate, 3 year survival rate, only 15% will be cured
 CLL: no definitive cure, 5 year survival rate is 60%
 CML: median survival time is 3.5 years, but any time from 1-12 years is possible
 If accelerated, less than 1 year, after blast crisis, may only live a few months