2. Leukemia
A group of malignant
disorders affecting the
blood and blood-
forming tissues of
Bone marrow
Lymph system
Spleen
Occurs in all age groups
3. DEFINITION
Leukemia are a group of neoplastic disorders affecting
mainly the leukopoietic tissues in the body and
characterized by the presence of leukocytosis,
immature leukocytes in the peripheral blood and
proliferation of these immature cells in the bone
marrow resulting in the suppression of normal tissue.
The abnormal cells infiltrate several organs in the
body.
-K.V Krishna Das, Mathew Thomas
4. Leukemia is a malignant disease characterized by
unregulated proliferation of one cell type
It may involve any of the cell lines or a stem cell common to
several cell lines.
5. TYPES
Acute Leukemia:
Affect younger age group frequently
Rapid course and the peripheral blood and bone marrow
show the presence of large number of blast cells.
If left untreated, these are fatal within weeks/ months
Chronic Leukemia:
Generally affect older people
onset is insidious
usually less aggressive
the cells involved are usually more mature cells
Terminate life within 2-3 yrs of onset.
6. Types….
Both acute and chronic leukemias are further classified according to the
prominent cell line involved in the expansion:
If the prominent cell line is of the myeloid series it is a myelocytic leukemia
(sometimes also called granulocytic)
If the prominent cell line is of the lymphoid series it is a lymphocytic
leukemia
Therefore, there are four basic types of leukemia
Acute myelocytic leukemia – AML- (includes myeloblastic,
promyelocytic, monocytic, myelomonocytic, erythrocytic, and
megakaryocytic)
Acute lymphocytic leukemia – ALL- (includes T cell, B cell, and Null
cell)
Chronic myelocytic leukemia – CML - (includes myelocytic and
myelomonocytic)
Chronic lymphocytic leukemia – CLL - (includes plasmocytic
{multiple myeloma}, Hairy cell, prolymphocytic, large granular cell
lymphocytic, Sezary’s syndrome, and circulating lymphoma)
11. Acute leukemia –
Is a result of:
Malignant transformation of a stem cell leading to unregulated
proliferation and
Arrest in maturation at the primitive blast stage. Remember that
a blast is the most immature cell that can be recognized as
committed to a particular cell line.
Clinical features
Leukemic proliferation, accumulation, and invasion of normal
tissues, including the liver, spleen, lymph nodes, central nervous
system, and skin, cause lesions ranging from rashes to tumors.
A humoral mediator from the leukemic cells may inhibit
proliferation of normal cells.
Failure of the bone marrow and normal hematopoiesis
may result in pancytopenia with death from
hemorrhaging and infections.
12. Difference between acute and
chronic leukemiaAcute leukemia Chronic leukemia
Age More in first and second decades but can occur in all age groups Mostly in the 4th, 5th and 6th decades but even young
children may be affected rarely
Sex ratio M:F= 2:1 1:1
Duration of symptoms Weeks to months Several months to one year
Presenting complaints Anemia, fever, infections, hemorrhagic tendencies or
complications, especially neurological
Vague symptoms, loss of weight, mass in abdomen, or
lymph nodular masses
Organomegaly Liver, spleen, lymph nodes are moderately enlarged in 70-80% of
cases
Moderate to gross splenomegaly is the rule in CML.
Moderate to gross lymphadenopathy in CLL
Blood picture WBC is moderately elevated (15-30×109/L),
Blast cells form 10-90% of total. Platelets are often reduced.
Elevated WBC(15-25×1010/L)
Bone marrow Showa depression of erythroid cells, myeloid cellsand
megakaryocytes and infiltration by the abnormal cells. Blast cells
form more than 30% and may be even upto 90%
CML shows increase in myeloid cells especially myelocytes,
metamyelocytes and neutrophils, infilteration by small
lymphocytes is seen in CLL. Erythroid and megakaryocytic
precursors show variable cellularity
Chromosomal studies Different pattern for different subtypes Ph chromosome present in 95% of cases
Course and prognosis Untreated- fatal within weeks to 6 months due to infections,
hemorrhage, anemia and other complications
Untreated- median survival of CML is 18-24 months.CLL
has more prolonged survival
Response to treatment Spontaneous remissions have rarely been reported. With modern
treatments, over proportion of 90% of cases go into remission and
60-70% get complete cure.
BMT- cure rate> 50%
13.
14. DIAGNOSIS OF LEUKEMIA
History and physical examination
Clinical features
Blood Examination(work up)
Peripheral blood examination
Chest X ray
Bone marrow studies: BM biopsy,
imprint and aspiration.
Flow cytometry
Cytological differentiation and
immunophenotyping: FISH,
RTPCR, chromosome analysis
15. TREATMENT
Goal is to attain remission (when there is no longer
evidence of cancer cells in the body)
Chemotherapeutic treatment
Induction therapy
Attempt to induce or bring remission
Seeks to destroy leukemic cells in the tissues, peripheral
blood, bone marrow
Patient may become critically ill
Provide psychological support as well
Intensification therapy
High-dose therapy
May be given after induction therapy
Same drugs at higher doses and/or other drugs
16. TREATMENT……
Chemotherapeutic
treatment (cont.)
Consolidation therapy
Started after remission is
achieved
Purpose is to eliminate
remaining leukemic cells
that may not be evident
Maintenance therapy
Lower doses of the same
drug
17. Leukemia
Chemotherapy Regimens
Combination chemotherapy
Mainstay treatment
3 purposes
↓ drug resistance
↓ drug toxicity to the patient by using multiple drugs with
varying toxicities
Interrupt cell growth at multiple points in the cell cycle
18. Leukemia - Bone Marrow and Stem Cell
Transplantation
Goal
Totally eliminate leukemic cells from the body using
combinations of chemotherapy with or without total
body irradiation
19.
20.
21. •Most common in children
•Arises from lymphoid tissue
•About 75% are null cell type,
20-25% are T cell type and
few are B cell type.
•Bimodal distribution
•Male:female= 2:1
22. ETIOLOGY
• Uncertain, but several proposed linkages:
· Genetic - Philadelphia chromosome
· Viral infection (EBV, HIV)
· Exposure to high energy radiation (T-cell ALL)
· Toxic chemical exposure
· Smoking
23. CLASSIFICATION
Immunologic
Subtype
% of Cases FAB
Subtype
Cytogenetic
Abnormalities
Pre-B ALL
T cell ALL
B cell ALL
75
20
5
L1, L2
L1, L2
L3
t(9;22), t(4;11), t(1;19)
14q11 or 7q34
t(8;14), t(8;22), t(2;8)
24. Acute leukemias- L1
L1 - This is the most
common form found in
children and it has the best
prognosis.
The cell size is small with
fine or clumped homogenous
nuclear chromatin and
absent or indistinct nucleoli.
The nuclear shape is regular,
occasionally clefting or
indented.
The cytoplasm is scant, with
slight to moderate basophilia
and variable vacuoles.
25.
26. Acute leukemias- L2
L2 – This is the most
frequent ALL found in
adults.
The cell size is large and
heterogenous with variable
nuclear chromatin and
prominent nucleoli.
The nucleus is irregular,
clefting and indented.
The cytoplasm is variable
and often moderate to
abundant with variable
basophilia and variable
vacuoles.
27.
28. Acute leukemias-L3 (BURKITT’S
LEUKEMIA)
L3 – This is the rarest
form of ALL.
The cell size is large, with
fine, homogenous nuclear
chromatin containing
prominent nucleoli.
The nucleus is regular oval
to round.
The cytoplasm is
moderately abundant and
is deeply basophilic and
vacuolated.
29.
30. ALL
ALL may also be classified on the basis of
immunologic markers into:
Early pre-B ALL
Pre-B ALL
B ALL
T ALL
Null or unclassified ALL (U ALL) - lack B or T
markers and may be the committed lymphoid
stem cell)
39. ALL – in contrast to the myeloblast, the
lymphoblast is a small blast with scant cytoplasm,
dense chromatin, indistinct nucleoli, and no auer
rods
40. Cytochemistry – help to classify the lineage of a
leukemic cell (myeloid versus lymphoid)
Myeloperoxidase – is found in the primary granules of
granulocytic cells starting at the late blast stage.
Monocytes may be weakly positive.
41. Sudan black Sudan black stains phospholipids, neutral fats
and sterols found in primary and secondary
granules of granulocytic cells and to a lesser
extent in monocytic lysosomes. Rare positives
occur in lymphoid cells
42. Nonspecific Esterase
Nonspecific esterase – is used to identify
monocytic cells which are diffusely positive. T
lymphocytes may have focal staining
43. Acid phosphatase
Acid phosphatase may be found in myeloblasts
and lymphoblasts. T lymphocytes have a high
level of acid phosphatase and this can be used to
help make a diagnosis of acute T-lymphocytic
leukemia.
44. Leukocyte Alkaline phosphatase
Leukocyte alkaline phosphatase – is located in the
secondary granules of segmented neutrophils, bands
and metamyelocytes. The LAP score is determined by
counting 100 mature neutrophils and bands. Each cell
is graded from 0 to 5. The total LAP score is calculated
by adding up the scores for each cell.
46. Immunologic markers (immunophenotyping) –
these are used mainly for lymphocytes, i.e., for
determining B cell or T cell lineage. These tests
rely on antibodies made against specific surface
markers.
They constitute what we would call the primary
antibody and in an indirect assay they are allowed to
react with the cells and unbound antibody is then
washed away.
Fluorescently labeled antibody (secondary antibody)
against the primary antibody is added and allowed to
react and then unbound secondary antibody is washed
away.
The cells are then sent through a flow cytometer that
will determine the number of cells that have a
fluorescent tag and which are thus positive for the
presence of the surface marker to which the primary
antibody was made.
In a direct assay, the primary antibody is fluorescently
labeled.
51. Terminal deoyxtidyl transferase
This is a unique DNA polymerase present in stem
cells and in precursor B and T lymphoid cells.
High levels are found in 90% of lymphoblastic
leukemias.
It can also be detected using appropriate
antibodies and flow cytometry.
52. Cytogenetics
cytogenetics studies can now be used for diagnosis
and for prognosis of hematologic malignancies.
Many leukemias (and lymphomas) are characterized by
specific chromosomal abnormalities, including specific
translocations and aneuploidy. The specific type of
malignancy can be identified based on the specific
abnormality or translocation. These may be identified
by
Looking at the karyotypes of the chromsomes from the
abnormal cells
DNA based tests – these tests are very useful for following the
course of the disease
RT-PCR
Southern blotting
A normal karyotype is usually associated with a better
prognosis.
56. ALL Treatment:
• Two phases of treatment
· induction
· post-remission
• Initial goal is to quickly induce complete
remission.
• Combination chemotherapy
• Continued low-dose post-remission therapy
must be used to ensure prolonged survival.
Otherwise recurrence rates can be as high as 90%
57. After Induction Chemotherapy:
• Bone marrow biopsy is obtained
• If >5% of blasts with >20% cellularity, then
retreatment necessary.
• Stem cell transplant may be necessary if
retreatment fails.
59. Continued Supporative Care:
• Transfusions….
· Platelets >20,000
· Hgb >8
• Empiric antibiotic treatment when fever present
• Allopurinol for increased uric acid levels
60. POOR PROGNOSTIC FACTORS
Age<1 and >20yrs (higher age >50yrs)
Males
Presence of mediastinal mass on X ray
Presence of organomegaly
Lab results: TC> 50000/cumm in B cell ALL and
>100000/cumm in T cell ALL
Immunophenotype: Blasts are T phenotype and presence
of Ph chromosome
Cytogenetic abnormalities: t(9;22), BCR/ABL or 11q23
abnormalities
Treatment response: late achievement of cure rate, multi
drug resistance, presesnse of blast cells in BM at 14 day.
61. NEUROLEUKEMIA
It occurs in 50% of ALL and 10-12% of AML cases, if neuro-
prophylaxis is not given along with initial therapy.
Pathological lesions include infiltration by leukemic cells,
hemorrhage, and demyelination.
Symptoms:
raised ICP
pappiledema
stupor, comma
focal neurological symptoms like convulsions or paralysis
cranial nerve palsies
spinal cord or spinal root compression
intracranial hemorrhage.
Hyper viscosity syndrome
62. TREATMENT
Neuroprophylaxis:
IT MTx :10-12mg/m2 twice a week for 6 doses. A single dose should
not exceed 15mg
IT cytosine arabinoside 50mg twice a week for 6 doses
CNS involvement should be diagnosed when the CSF count
> 5/cumm with or without the presence of blast cells.
Treatment:
Cranial or craniospinal irradiation combined with IT MTx/ cytosine
63.
64.
65. TESTICULAR LEUKEMIA
The testes may be
enlarged, firm and tender,
or involvement may be
clinically inapparent.
Testicular involvement
may leads to relapse.
Treatment is by irradiation
with 1000-2000 rads over a
period of 2-10 days.
Higher incidence of
sterility limits its routine
application
70. CLASSIFICATION
Stagin
g
system
Stage Modified three stage system Clinical findings Media
n
surviva
l
(years)
Rai 0 Low risk Lymphocytes in blood and marrow
only
>10
I Intermediate risk Lymphocytosis+
lymphadenopathy+splenomegaly±he
patomegaly
7
II
High risk
Lymphocytosis+ anaemia and / or
thrombocytopenia
1.5III
IV
Binet A <3 node bearing areas >10
B ≥3 node bearing areas 5
C anaemia and / or thrombocytopenia 2
73. Hematological
Findings:
• Increased number of
lymphocytes on smear
·smudge cells
• B-cells with CD 19
and CD 5 on flow
cytometry
• Small lymphocitic
lymphoma present in
histology of nodal
biopsy
76. DIAGNOSIS
Peripheral blood lymphocytosis: an absolute lymphocyte
count > 5000/cumm, with cells that appears
morphologically mature.
Immunophenotype of blood lymphocytes that coexpress B
cell antigens CD19, 20 and 23, as well as T cell antigen CD5;
monoclonal expression of either kappa or lambda light
chain; and low density surface immunoglobulin secretion
BM examination is not a requirement when both of the
above criteria are met, but it is useful for prognostic
information. Lymphoid cells must constitute more than
30% of cells
The peripheral blood is sent for flow cytometry to assess
immunophenotype of cells
77. Increase in blood lymphocyte count
Demonstrate presence of a B-lymphocyte clone of
appropriate immunophenotype
Surface marker analysis – ‘flow cytometry’
79. MEDICAL MANAGEMENT
Single agent chemotherapy: chlorambucil, 6-14mg, PO
every 2-4 weeks. PDN increases response rate
Nucleoside analogue: Fludarabine
Combination chemotherapy: fludarabine+
cychlophosphamide, fludarabine+ rituxan
Monoclonal antibody: rituxan+ alemtuzumab
Stem cell transplantation
80.
81. PROGNOSTIC FACTORS
Age and sex: increased age, poor prognosis. Female
survive more than males
Lymphocyte doubling time: LDT is the rate at which
the lymphocyte count increases, correlate with
survival. LDT > 12 months, better outcome
Beta 2 microglobulin: a low level indicates good
survival
Cytogenetics: most unfavorable abnormality is del 17p
and is associated with refractory to fludarabine
82. Leukemia characterized by proliferation of myeloid
tissue (as of the bone marrow and spleen) and an
abnormal increase in the number of granulocytes,
myelocytes, and myeloblasts in the circulating blood
83. AML arises from common precursor stem cell and is
divided into7 types –M1 to M7
85. CLASSIFICATION
It depends upon
Bone marrow blast
morphology
Degree of cell
maturation
Cytochemical stains
Immunophenotyping
AML is divided into 7
different classifications:
86. Acute Myeloid Leukemia (AML):
Classification/Subtypes:
• French-American-British Classification
· eight major subtypes
· based on morphology and cytochemistry
• World Health Organization Classification
· based on molecular, morphologic, and clinical features
87. Subtype FAB Type Morphology Cytogenetic Abnl
AML w/o maturation M0 no azurophil granules -
AML M1 few Aeur rods del(5); del(7); +8
AML w/ differentiation M2
maturation beyond
promyelocytes; Auer rods t(8:21) t(6:9)
Acute Promyelocitic Leukemia M3
hypergranular
promyelocytes; Auer rods t(15:17)
Acute Myelomonocytic Leukemia M4
> 20% monocytes;
monocytoid cells in blood
inv(16) del(16) t(16:16)
t(4:11)
Acute Monocytic Leukemia M5 monoblastic; promonocytic t(9:11) t(10:11)
Acute Erythroleukemia M6
predominance of
erythroblasts;
dyserythropoiesis -
Acute Megakaryocytic Leukemia M7
dry' aspirate; biopsy
dysplastic with blasts -
Classification of AML
88. AML-M1
M1 – myeloblastic
without maturation
The bone marrow shows
90% blasts and < 10%
promyelocytes
The disease occurs in
older adults
Note the myeloblasts
and the auer rod:
89. AML – M2
Note myeloblasts and
hypogranulated PMNs:
M2 – myeloblastic with
maturation
The bone marrow shows
30-89% blasts and >
10% promyelocytes;
This is characterized by
an 8,21 chromosomal
translocation
This occurs in older
adults
90. AML – M3
Note hypergranular
promyelocytes:
M3 – hypergranular
promyelocytic
This form of AML has a bone
marrow with >30% blasts
Is more virulent than other
forms
Occurs with a medium age of
39
The WBC count is decreased
Treatment causes a release of
the granules and may send
the patient into disseminated
intravascular coagulation and
subsequent bleeding
It is characterized by a 15,17
chromosomal translocation
91. AML – M3M
Note hypogranular
promyelocytes:
M3m – hypogranular
promyelocytic –
The bone marrow has >
30% blasts
The WBC count is
increased.
Like the M3 type,
treatment causes a release
of the granules and may
send the patient into
disseminated intravascular
coagulation and
subsequent bleeding and
It is characterized by a
15,17 translocation
92. AML – M4
Note monoblasts and
promonocytes:
M4 – acute
myelomonoblastic
leukemia
Both myeloblasts and
monoblasts are seen in
the bone marrow and
peripheral blood
Infiltration of
extramedullary sites is
more common than
with the pure
granulocytic variants
93. AML – M5A
Note monoblasts: M5 – acute monoblastic
leukemia
>80% of the nonerythroid
cells in the bone marrow
are monocytic
There is extensive
infiltration of the gums,
CNS, lymph nodes and
extramedullary sites
This form is further
divided into
M5A - Poorly differentiated
(>80% monoblasts)
M5B - Well differentiated
(<80% monoblasts)
95. AML – M6
Note M1 type monoblasts M6 – erythroleukemia
This is rare and is
characterized by a bone
marrow having a
predominance of
erythroblasts
It has 3 sequentially
morphologically defined
phases;
Preponderance of abnormal
erythroblasts
Erythroleukemia – there is an
increase in both erythroblasts
and myeloblasts
Myeloblastic leukemia – M1,
M2, or M4
Anemia is common
96. AML-M7
M7 - Acute
megkaryoblastic
leukemia
This is a rare disorder
characterized by
extensive proliferation
of megakaryoblasts,
atypical megakaryocytes
and thrombocytopenia
98. DIAGNOSIS
Peripheral examination
Blood Examination
Abnormalities in one or more organ system due to
leukemic infilteration
Rarely granulocytic sarcoma( solid mass of leukemic
cells)
BM biopsy and aspiration
Immunophenotyping and cytogenetic study to
determine treatment
103. ACUTE PROMYELOCYTIC
LEUKEMIA (APML)
APML is characterized by bleeding tendency caused
by DIC.
Patient presents with heavy bleeding or frank DIC.
BM is filled with heavily granulated progranulocytes.
Diagnosis is done by BMB and BMA.
104. There is translocation of
chromosomes 15 and 17.
The genes for retinoic acid
receptor (RAR) alpha on
chromosome 15 fuses with
the promyelocytic
leukemic gene (PML) on
chromosome 17, resulting
in formation of PML RARA
fusion product.
ATRA is the treatment of
choice of APML. Dose
45mg/m2 body surface
area/day for 15 days, once
in three months as
maintenance therapy.
105.
106.
107. TREATMENT: ACUTE MYELOID
LEUKEMIA
There are 2 goals:
Eradicate the leukemic cell mass
Give supportive care
Except for ALL in children, cures are not common but
complete remission (absence of any leukemia related
signs and symptoms and return of bone marrow and
peripheral blood values to within normal values) is
achievable.
108. TREATMENT: ACUTE MYELOID
LEUKEMIA
AML protocol:
Induction phase 3+7 or 7+3
Daunorubucin 45mg/m2 IV D1-D3
Cytarabine 100mg/m2/d IV for 7 days (continuous infusion)
Or
Idarubicin 12mg/m2 IV D1-D3
Cytarabine 100mg/m2/d IV for 7 days (continuous infusion)
Repeat cycles every 4-6 wks for upto a total of 3 cycles
BM Examination on day 14 from the first day of chemotherapy to assess response.
Positive response: hypocellular , aplastic marrow
Peripheral Smear: marrow aplasia, with profound neutropenia and
thrombocytopenia at 14 day of nadir period.
If persistent leukemia:,Repeat the course for further induction despite of
pancytopenia
For APML: ATRA 45mg/m2 PO daily along with 7+3 regimen/ arsenic trioxide
109. Consolidation phase(HIDAC)
Cytarabine 3g/m2 every 12hr IV D1, D3 and D5 (over 3 hr
period for 6 doses)
Inj. Daunorubicin 45mg/m2 IV on D1,2
Repeat the course for 4 courses every 21-28 days
Complication: risk for ocular problems and neurotoxicity.
Prevention of ocular problem is done by corticosteroid
eyedrops and pretreatment assessment of neurologic status
helps to identify neuro toxicity.
AML relapse: FLAG relapse
Fludarabine 25 mg/m2 IV on D1-5
Cytarabine 2g/m2 IV/day IV over 4 hrs on D1-5 starting 3.5
hrs after fludarabine
GCSF 300µgm s/c until hematopoietic recovery
110. •A neoplasm of hemopoietic stem cells caused by the
‘Philadelphia’ chromosome t(9;22)
•A two-phase disease
111. DEFINITION
The diagnosis of CML is established by identifying a
clonal expansion of a hematopoietic stem cell
possessing a reciprocal translocation between
chromosomes 9 and 22.
115. Chronic Myeloid Leukemia (CML):
Three Phases:
• Chronic phase: 3-5 years. Current treatment is with alpha-
interferon. Young patients should undergo BMT.
• Accelerated phase: New nonrandom cytogenic abnormalities in
up to 80% of patients. Difficult to control. Development of myelofibrosis.
Elevated leukocyte counts. Lasts several months before becoming blastic.
• Blast phase: > 30% blasts in blood or marrow. Treatment with
chemotherapy similar to acute leukemia. Some patients go into remission
with treatment, but it is short lived.
124. The bcr/abl fusion protein
Uncontrolled kinase
activity
1. Deregulated cellular
proliferation
2. Decreased adherence of
leukemia cells to the bone
marrow stroma
3. Leukemic cells are
protected from normal
programmed cell death
(apoptosis)
125. CLINICAL PRESENTATION
Peak age 20 to 40 years
Weight loss, night sweats
Big spleen
Gout
Often found by chance
127. Laboratory features
The hemoglobin concentration is decreased
Nucleated red cells in blood film
The leukocyte count above 25000/μl (often above 100000/μl),
granulocytes at all stages of development
Hypersegmentated neutrophils
The basophiles count is increased
The platelet count is normal or increased
Neutrophils alkaline phosphatase activity is low or absent
(90%)
128. Laboratory features
The marrow is hypercellular (granulocytic hyperplasia)
Reticulin fibrosis
Hyperuricemia and hyperuricosuria
Serum vitamin B12-binding proteine and serum vitamin B12
levels are increased
Pseudohyperkalemia, and spurious hypoxemia and
hypoglycemia
Cytogenetic test- presence of the Ph chromosome
Molecular test – presence of the BCR-ABL fusion gene
130. CML - principles of treatment
Imatinib mesylate to achieve a
‘Major Molecular Remission’ (by
Q-RT-PCR)
Allogeneic transplantation
Hydroxyurea
131. Traetment
Imatinib mesylate (Gleevec)
• Inhibits activity of mutant tyrosine kinase by blocking ATP binding
• Very useful in older patients or patients intolerant or resistance to
interferon-alfa
• Imatinib has less toxicity, is easier to administer , and induces higher
hematologic (90 percent vs. 75percent), cytogenetic (40 percent vs. 10
percent) and molecular (7 percent vs. 2 percent) types of remission
• Dose: 400mg/d orally (maximal dose 600-800mg/d in two divided doses)
• Usually after 3-9 months of treatment – cytogenetic response
132.
133. Criteria of cytogenetic response
Cytogenetic response % of Ph in bone marrow
complete 0
maior 1-35
minor 36-95
lack of response >95
134. Criteria of molecular response
Complete molecular response:
BCR/ABL transcript undetectable in PCR
Maior molecular response:
≥3-log reduction of BCR/ABL transcript in RQ-PCR
136. HAIRY CELL LEUKEMIA
2% of all adult leukemias
Usually in males > 40 years
old
Chronic disease of
lymphoproliferation
B lymphocytes that infiltrate the
bone marrow and liver
Cells have a “hairy”
appearance
Symptoms from
Splenomegaly, pancytopenia,
infection, vasculitis
Treatment
alpha-interferon, pentostatin,
cladribine
137. Acute Myeloid Leukemia (AML):
Remission:
• Combination tx with cytarabine/daunorubicin
• 65-75% will achieve CR. Two-thirds achieve CR
after a single cycle. The other one-third after a
second course.
• 50% of those who do not achieve CR fail because
of a drug-resistant leukemia. The other 50%
because of fatal complications of bone marrow or
stem cells.
138. Acute Lymphoid Leukemia (ALL):
Remission:
• Combination tx with daunorubicin, vincristine,
prednisone, and asparaginase
• Childhood ALL CR rate is approximately 90-
95%
• Adult ALL CR rate is approximately 70-80%
139. Chronic Myeloid Leukemia (CML):
Remission:
• With concominant BMT and alpha-interferon
treatment, remission rates of 40-60% can be
achieved.
• Relapse rate is high, and median survival is only
5-6 years.
140. Chronic Lymphoid Leukemia (CLL):
Remission:
• Remission has not been achieved in CLL.
• Treatment with chemotherapy (fludarabine,
CHOP, or CVP) increases median survival rates:
· Stage 0-I: 10-15 years
· Stage II-IV: approximately 2-5 years for 90%
of patients
141. Prognostic
Factor Survival
5 year survival is 10-35% for all patients
with AML
5-10% will survive more than 5 years
20-35% for young patients who undergo
chemotherapy and BMT
Children 60-70% 5-year disease free survival
Adults 25-35% 5-year survival
CML Median survival 5-6 years
Stage O > 15 years
Stage I 9 years
Stage II 5 years
Stage III and IV 2 years
CLL
AML
ALL
142.
143. Assessment
Skin: Check for tenderness, edema, breaks in skin integrity, moisture,
drainage, lesions (especially under breasts, axillae, groin,skin folds, bony
prominences, perineum); check all puncture sites (eg, intravenous sites)
for signs and symptoms of inflammation/infection.
Oral mucosa: Check for moisture, lesions, color (check palate, tongue,
buccal mucosa, gums, lips, oropharynx).
Respiratory: Check for presence of cough, sore throat; auscultate breath
sounds.
Gastrointestinal: Check for abdominal discomfort/distention, nausea,
change in bowel pattern; auscultate bowel sounds.
Genitourinary: Check for dysuria, urgency, frequency; check urine for color,
clarity, odor.
Neurologic: Check for complaints of headache, neck stiffness, visual
disturbances; assess level of consciousness, orientation, behavior.
Temperature: Check every 4 hr or every visit; call primary health care
provider if temperature is >38°C (>101°F), fever is unresponsive to
acetaminophen, or patient shows a decline in hemodynamic status.
144. Laboratory Tests
Monitor complete blood count (CBC) and differential daily (especially
absolute neutrophil count [ANC], lymphocyte count); coagulation panel.
Call physician if ANC is <1000, significantly different from previous count,
or whenever patient becomes symptomatic (eg, febrile). Notify physician if
platelet count is <10,000/mm3 or if count has changed significantly from
previous count (including coagulation), or whenever patient becomes
symptomatic.
Ensure patient’s blood was human leukocyte antigen (HLA) typed before
transfusions or chemotherapy begins if admitted for induction therapy (eg,
for acute leukemia).
Obtain 1-hour posttransfusion platelet count if warranted.
Test all urine, emesis, stools for occult blood.
Monitor globulin, albumin, total protein levels.
Monitor all culture and sensitivity reports.
Monitor radiology reports.
146. Risk for infection
secondary to
impaired immunoincompetence due to:
Diminished neutrophil count secondary to bone marrow
invasion or hypocellularity secondary to medications
Dysfunctional neutrophils (eg, secondary to myelodysplastic
syndrome [MDS])
Dysfunctional or diminished lymphocytes
Malnutrition
Surgery or invasive procedures
Antibiotic therapy (increased risk for superimposed
infection)
147. Potential bleeding and injury
secondary to
thrombocytopenia/altered coagulation due to:
Malignant invasion in bone marrow
Bone marrow suppression resulting from chemotherapy
(particularly alkylators, antitumor antibiotics,
antimetabolites) and radiation therapy
Hypersplenism
Disseminated intravascular coagulation (DIC)
Altered coagulation
148. Risk for impaired skin integrity related to toxic effects
of chemotherapy, alteration in nutrition, and impaired
mobility
Impaired gas exchange
Impaired mucous membranes related to changes in
epithelial lining of the gastrointestinal tract from
chemotherapy or prolonged use of antimicrobial
medications
Imbalanced nutrition, less than body requirements,
related to hypermetabolic state, anorexia, mucositis,
pain, and nausea
149. Acute pain and discomfort related to mucositis, WBC
infiltration of systemic tissues, fever, and infection
Hyperthermia related to tumor lysis and infection
Fatigue and activity intolerance related to anemia and
infection
Impaired physical mobility due to anemia and
protective isolation
150. Risk for excess fluid volume related to renal
dysfunction, hypoproteinemia, need for multiple
intravenous medications and blood products
Diarrhea due to altered gastrointestinal flora, mucosal
denudation
Risk for deficient fluid volume related to potential for
diarrhea, bleeding, infection, and increased metabolic
rate
Self-care deficit due to fatigue, malaise, and protective
isolation
151. Anxiety due to knowledge deficit and uncertain future
Disturbed body image related to change in
appearance, function, and roles
Grieving related to anticipatory loss and altered role
functioning
Potential for spiritual distress
Deficient knowledge about disease process, treatment,
complication management, and self-care measures
152. General Nursing Interventions
Thorough hand hygiene must be done by everyone before entering
patient’s room each and every time.
Allow no one with a cold or sore throat to care for the patient or to enter
room, or come in contact with patient at home.
Care for neutropenic patients before caring for other patients (as much
as possible).
Use private room for patient if ANC is <1000.
Allow no fresh flowers (stagnant water).
Change water in containers every shift (include O2 humidification
systems every 24 hr).
Ensure room is cleaned daily.
Provide low microbial diet.
Eliminate fresh salads and unpeeled fresh fruits or vegetables.
Avoid suppositories, enemas, rectal temperatures.
153. General Nursing Interventions…
Practice deep breathing (with incentive spirometer) every 4 hr
while awake.
Ambulate; wear high-efficiency particulate air (HEPA) filter
mask if neutropenia is severe.
Prevent skin dryness with water-soluble lubricants, especially in
high-risk areas (eg, lips, corners of mouth, elbows, feet, bony
prominences).
Provide meticulous total body hygiene daily (preferably with
antimicrobial solution), including perineal care after every bowel
movement.
Provide thorough oral hygiene after meals and every 4 hr while
awake; warm saline, or salt and soda solution, is effective; avoid
use of lemon-glycerine swabs, commercial mouthwashes, and
hydrogen peroxide.
154. General Nursing Interventions…
Do not use plastic cannulas for peripheral IVs when ANC is <500
(if possible per agency); a central vascular access device is
preferred for long-term or intensive IV therapy.
Inspect IV sites every shift; monitor closely for any discomfort;
erythema may not be present.
Maintain meticulous IV site care.
Cleanse skin with antimicrobial solution before venipuncture
(unless patient is allergic).
Moisture-vapor–permeable dressings are permissible with strict
adherence to institutional protocol.
Change IV tubing per institution policy, using aseptic technique.
Administer antimicrobial agents on time.
156. Bone marrow Suppression
Anemia:
Monitor hematocrit, Hb especially during nadir period
PRC transfusion
Diet modification
Encourage fluid intake
Neutropenia care:
Monitor CBC daily including ANC
Monitor vital signs to know hyperthermia
Incase of fever, blood C&S to identify organism
Aseptic technique while caring patient
Educate patient and family regarding nadir period and neutropenia
Encourage to drink atleast 2L fluid
Maintain I/O chart and hydration status
Dietary modification: High calory high protein diet. Avoid fresh fruits and grapes
Maintain hygiene: bath daily, change clothes daily
Administration of GCSF
Antibacterial, antuviral and antifungal treatment
Avoid visitors and contact with people with communicable disease
Avoid live vaccine
157. Prevent Complications: Bleeding
Avoid aspirin and aspirin-containing medications or other medications known to inhibit
platelet function, if possible.
Do not give intramuscular injections.
Do not insert indwelling catheters.
Take no rectal temperatures; do not give suppositories, enemas.
Use stool softeners, oral laxatives to prevent constipation.
Use smallest possible needles when performing venipuncture.
Apply pressure to venipuncture sites for 5 min or until bleeding has stopped.
Permit no flossing of teeth and no commercial mouthwashes.
Use only soft-bristled toothbrush for mouth care.
Use only toothettes for mouth care if platelet count is <10,000/mm3, or if gums bleed.
Lubricate lips with water-soluble lubricant every 2 hr while awake.
Avoid suctioning if at all possible; if unavoidable, use only gentle suctioning.
Discourage vigorous coughing or blowing of the nose.
Use only electric razor for shaving.
Pad side rails as needed.
Prevent falls by ambulating with patient as necessary.
Apply direct pressure.
For epistaxis, position patient in high Fowler’s position; apply ice pack to back of neck and
direct pressure to nose.
Notify physician for prolonged bleeding (eg, unable to stop within 10 min).
Administer platelets, fresh frozen plasma, packed red blood cells, as prescribed.
158. GI problems: Mucositis, stomatitis, esophagitis
due to destruction epithelial cells
Assess oral mucosa daily and teach patient to do this
Use mucositis assessment scale such as OEG, OPG, WCCNR scale
Use dendrifies and rinces
Instruct patient to inform if he has any pain, ulceration or dysphagia
Instruct to avoid irritant like tobacco, alcohol, spicy foods etc
Encourage to use artificial saliva incase of xerostomia
Encourage oral fluids and maintain hydration
Instruct to use chlorhexidine mouth wash two hourly
Encourage small and frequent feeding
In case of mucositis : instruct to take sodabicarbonate mouth wash
Saline irrigation of mouth ulcers
Ryles tube feeding/ TPN/ IV hydration
Apply topical anaesthetics like zytee gel, xylocaine gel
Anti fungal agents: candid mouth paint/ co-trimoxazole
Antiviral prophylais with acyclovir
Mucosal protectors: hydroxyl propyl cellulose
Systemic antibiotics, antifungals, analgesics, anti inflammatory agents etc
Mucosal protectors such as sucralfate, amifostine etc
To prevent bleeding from mouth: oral care with cotton, soft bristled brush, ice water irrigation.
Adrenaline packes incase of bleeding
159. Nausea and vomiting due to intracellular
breakdown products which stimulate vomiting centre
Aseess characteristics of vomiting: amount, frequency, colour
Encourage fluid intake
Monitor daily weight
Monitor vital signs and I/o chart
Administer prophylactic antiemetics such as ondaseteron,
Medications include: 5HT3 receptor antagonist(ondaseterone, graniseteron,
palanoseterone)
Neurokinin1 receptor antagonist(aprepitant)
Dopamine receptor antagonist(promethacine- phenergan, metachlopromide-
perinorm)
Anti histamines
Benzodiazepines to reduce anxiety: lorazepam. Alprax
Steroids: dexona
Non pharmacological measures such as environmental modification, behavioral
therapy, diet modification, acupressure(p6 point and ST36 point), progressive
muscle relaxation
160. Constipation due to decreased GI motility
/diarrhea due to side effects of CT
Assess bowel pattern
Encourage activity. Plan activity and rest periods
Encourage fluid intake
Low fiber diet for diarrhea and high fiber diet for
constipation
161. For constipation
• Laxatives
First line stimulant laxatives: Bisacodyl
Second line fecal softeners: liquid paraffin
Third line osmotic agents: lactulose, phosphate enema
• Bulk forming agents: methyl cellulose
• Rectal agents: Bisacodyl suppositories
For diarrhea
• For peudomembraneous colitis- metronidazole
• Profused watery diarrhea- somatostain
analogue(octreotide)
• Opioid drug - lopramide
162. Fatigue
Assess activity level and nutritional status
Encourage rest
Nutritious diet and more fluid intake
163. Alopecia( disturbed body image) due to
destruction of hair follicle by
chemodrugs
Explain about chance of alopecia and ways to cope with
that
Cut long hairs before therapy
Avoid excess shampooing, combing etc
Avoid electric hair dryers, curling rods
Educate that hair loss is reversible
Provide psychological support
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K.V Krishnadas. Textbook of Medicine. 5th ed. Delhi: Jaypee
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Chintamani. Lewis’s Medical Surgical Nursing.1st ed. India: Mosby’s
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