LEUKEMIA

✓ The term leukocytosis refers to an

increased level of leukocytes (WBCs) in
circulation.
✓ Because the proportions of several types
of leukocytes (e.,g., eosinophils, basophils,
monocytes) are small, an increase in one
type can be great enough to elevate the
total leukocyte count.
✓A prolonged or progressively increasing elevation
in leukocytes is abnormal and should be evaluated.
✓The common feature of the leukemias is the
unregulated proliferation of leukocytes in the bone
marrow.
✓In acute forms (or late stages of chronic forms) the
proliferation of the leukemic cells leaves little room
for normal cell production.
✓With acute forms, there can be infiltration
pf leukemic cells in the organs, such as the
meninges, lymph nodes, gums, and skin.
✓The cause of leukemia is not fully known but
there is some evidence of genetic and viral
influence.
✓Bone marrow damage from radiation
exposure, or from chemicals such as
benzene and alkylating agents.
✓The leukemia are commonly classified
according to the the stem cell in line
involved, either lymphoid (referring to stem
cells that produce lymphocytes) or myeloid
(referring to stem cells that produce
nonlymphoid blood cells).
✓They are also classified either acute or
chronic, based on the time it takes for
symptoms to evolve and the phase of cell
development is halted.
✓In acute leukemia, the onset of symptoms is
abrupt, often occurring within a few weeks.
✓Leukocyte development is halted at the
blast phase and thus most leukocytes are
undifferentiated cells or blasts.
✓Acute leukemia can progress rapidly, with
death occurring within weeks to months
without aggressive treatment.
✓In chronic leukemia, symptoms evolve over
a period of months to years and the
majority of the leukocytes produced are
mature.
✓Chronic leukemia progresses more slowly,
the disease trajectory can extend for years.
 ACUTE MYELOID LEUKEMIA
✓ Acute myeloid leukemia (AML) results from the defect in the
hematopoietic stem cells that differentiates into all myeloid
cells;
✓ monocytes, granulocytes (e.,g., neutrophil, basophils,
eosinophils )
✓ erythrocytes and platelets.
ACUTE MYELOID LEUKEMIA
✓ Any group age can be affected, although
infrequently occurs before age 55 years,
and the incidence rises with age , with a
peak incidence at the age 67 years.
✓ The prognosis is highly variable. Patient age
is a significant factor
 ACUTE MYELOID LEUKEMIA
✓ Patient who are younger may survive for 5 years or more
after diagnosis of AML.
✓ Patients who are older than 60 years, have a more
undifferentiated form of AML, have central nervous system
(CNS) involvement, or have a systematic infection at the
time of diagnosis tend to have worsen prognosis.
✓ The 5-year survival rate for patients who have AML who
are 50 year of age or younger is 43% it drops to 19%for
those between 50 and 64 years.
 CLINICAL MANIFESTATIONS
➢ AML develops without warning:Signs and symptoms
result from insufficient production of normal blood
cells.
➢Fever and infection result from neutropenia
(low neutrophil count;
➢weakness and fatigue,
➢dyspnea on exertion and pallor from anemia;
➢petechiae, ecchymoses and bleeding
tendencies from thrombocytopenia.
 CLINICAL MANIFESTATIONS
➢The proliferation of leukemic cells within organ
leads to a variety of additional symptoms:
➢ pain from an enlarged liver or spleen, hyperplasia
of the gums, and bone pain from expansion of
marrow.
➢Petechiae (pinpoint red or purple hemorrhagic
spots on the skin) and ecchymoses (bruises) are
common on the skin, occasionally leukemic
infiltrates are also seen.
 CLINICAL MANIFESTATIONS

➢Leukemic cells also infiltrates the gums and joints,

➢Lymphadenopathy and splenomegaly is rare.
➢Fevers may occur and are not always due to
infection
 ASSESSMENT AND DIAGNOSTIC
FINDINGS
➢CBC shows a decrease, in both erythrocytes and
platelets.
➢Although the total leukocytes count can be low,
normal, or high the percentage of normal cells is
usually vastly decreased.
➢ A bone marrow analysis shows and excess
immature blast cells (immature leukocytes) more
than 20% which is the hallmark of the diagnosis
 ASSESSMENT AND DIAGNOSTIC
FINDINGS
➢ The actual prognosis rises varies somewhat between 7
subgroups and with the extent of cytogenetic abnormalities
and genetic mutations
➢ yet the clinical course and treatment differ substantially
with only one prototype.
➢ Patients with acute promyelocytic leukemia (APL, or AML-
M3) often have significantly more problems with bleeding
in that they have underlying coagulopathy and a higher
incidence of DIC (Franchini, Di Minno, and Coppola, 2010)
 MEDICAL MANAGEMENT
✓ The overall objective of treatment is to achieve complete
remission, in which there is no evidence of residual
leukemia in the bone marrow,

✓ Attempts are complete to achieve remission by the

aggressive admission of chemotherapy, called induction
therapy which usually requires hospitalization for several
weeks.
 MEDICAL MANAGEMENT
✓ Induction therapy typically involves high doses of
cytarabine (Cystosar, Ara-C) and
✓ daunorubicin (Cerubidine) or mitoxantrone (Novantrone)
or idarubicin (Idamycin) sometimes etoposide (VP-16
VePesid) is added to the regimen.
✓ The choice of agents is based on the patients medical
status and history of prior antineoplastic treatment.
✓ Treatment of APL revolves around induction therapy
using the differentiating agent all-trans retinoic acid
(ATRA), which induces the promyelocytic blast cells to
differentiate.
 MEDICAL MANAGEMENT
✓ ATRA is typically combined with a conventional
chemotherapeutic agent, usually an anthracycline drug.
The regimen yields a very high response rate, and cure
is possible (Stein and Tallman, 2012)
✓ The aim of induction therapy is to eradicate leukemic
cells; however this is also accompanied by the
eradication of normal types of myeloid cells.
✓ The patient becomes severely neutropenic (an absolute
neutrophil count) [ANC; a precise calculation of the
number of circulating neutrophils] of 0 is not uncommon).
 MEDICAL MANAGEMENT
✓ Anemic and thrombocytopenic ( a platelet count of less
than 5,000/mm3 ic common.
✓ During this time the patient is typically ill, with
bacterial, fungal, and occasionally vital infections;
bleeding and severe mucositis, which causes
diarrhea and an inability to maintain adequate
nutrition.
✓ Management consist of administering blood products
(packed red blood cells [PRBCs] and platelets and
promptly treating infections.
 MEDICAL MANAGEMENT

✓ The use of granulocytic growth factors, either

granulocyte colony-stimulating factor (G-CSF);
filgastrim (Neupogen) or granulocyte-
macrophage colony-stimulating factor (GM-
CSF; sargramostism [Leukinel],
✓ These can shorten the period of significant
neutropenia by stimulating the bone marrow to
produce leukocytes more quickly; these agents do
not appear to increase the risk of producing more
leukemic cells (NCI, 2012a)
 MEDICAL MANAGEMENT

✓When the patient recovered from the

induction therapy (i.,e., the neutrophil and
platelet counts have returned to normal and
any infection had resolved),
✓consolidation, (post-remission) therapy is
administered to eliminate any residual
leukemia cells that are not clinically
detachable and reduce the chance of
recurrent.
 MEDICAL MANAGEMENT

✓Frequently the patient receives one cycle of

treatment that is almost the same as, if not
identical to, the induction treatment but at
lower dosages, therefore resulting in less
toxicity (Burnett, 2012)
✓Another aggressive treatment option is
hematopoietic stem cell
transplantation(HSCT)
 MEDICAL MANAGEMENT

✓When a suitable tissue can be match and

can be obtained, the patient embarks on an
even more aggressive regimen of
chemotherapy (sometimes in combination
with radiation therapy), with the treatment
goal of destroying the hematopoietic
function of the patient’s bone marrow.
 MEDICAL MANAGEMENT

✓The patient’s who undergo HSCT have a

significant risk of infection, graft-versus-
host-disease (in which the donor’s
lymphocytes [graft] recognize the
patient’s body as foreign and set up
reactions to attract the foreign host) and
other complications.
 MEDICAL MANAGEMENT

✓Patient’s with a poorer diagnosis may

benefit from early HCST, those with a
good prognosis may not tend to
transplant at all.
✓Another transplant option for the patient
to consider is supportive care alone.
 MEDICAL MANAGEMENT

✓A patient with comorbidity such as

extremely poor cardiac, pulmonary,
renal, or hepatic function and/or is
older and frail.
✓Supportive care option may be
significant.
✓In such cases aggressive antileukemia
therapy is not used.
 MEDICAL MANAGEMENT
✓Ocassionally hydroxyurea (Hydrea) or low doses
of cytarabine may be used briefly to increase the
blast cells.
✓Patients are more commonly supported with
antimicrobial therapy and transfusions as
needed.
✓This treatment approach provides the patient with
some additional time outside the hospital;
however death frequently occurs within months,
typically from infection or bleeding.
 COMPLICATIONS
include bleeding and infection, which are the
major causes of death.
✓The risk of bleeding correlates with the level and
duration of the platelet deficiency
(thrombocytopenia)
✓The low platelet count can cause ecchymoses
(bruises) petechiae.
✓Major hemorrhage also may develop when the
platelet count drops to less than 10,000/mm3
 COMPLICATIONS
✓The most common bleeding sources :
gastrointestinal (GI), pulmonary, vaginal, and
intracranial.
✓Fever and infection also increase the likelihood of
bleeding.
✓DIC is common particularly in patiens with APL
(Franchini, et.al.2010)
✓A very high WBC count (greater than 100,000 *
10 raise to 9/L can cause stasis within the
cerebral or pulmonary circulation.
 COMPLICATIONS
✓Infection increases with the degree and duration of
neutropenia; neutrophil counts that persist at less
than 100 /mm3 dramatically increase the risk of
systemic functions.
✓As the duration of severe neutropenia increases, the
patients risk of developing fungal infections
increases.
✓Fungal infections remain difficult to treat despite the
development of new antifungal agents, particularly if
the patient has persistent neutropenia
 COMPLICATIONS
✓Massive leukemic cell destruction from
chemotherapy results in the release of intracellular
electrolytes and fluids into the systemic circulation.
✓Increases in uric acid levels, potassium and
phosphate are seen, this process is referred to
as tumor lysis (cell destruction) syndrome.
✓The increases uric acid and phosphorus levels
make the patient vulnerable to renal stone formation
and renal colic, which can progress to renal acute
failure.
 COMPLICATIONS
✓Hyperkalemia and hypocalcemia can lead to
cardiac dysrhythmias; hypotension; neuromuscular
effects such as muscle cramps, weakness, and
spasm/intake and prophylaxis with allopurinol
(Zyloprim) to prevent crystallization of uric acid
and subsequent stone formation
✓GI problem may result from the infiltration of
abnormal leukocytes into the abdominal organs and
from the toxicity of the chemotherapeutic agents.
●CHRONIC
MYELOID
LEUKEMIA
 CHRONIC MYELOID LEUKEMIA
✓ Chronic myeloid leukemia (CML) arises from the mutation
of the myeloid stem cell.
✓ Normal myeloid cells continue to be produced, but there is
no pathologic increase in the production of forms of blast
cells.
✓ Causes an uncontrolled proliferation of cells, the marrow
expands into the cavities of long bones, such as the femur,
and cells are also formed in the liver and spleen,
(extramedullary hematopoiesis) resulting in enlargement of
of these organs that is sometimes painful
 CHRONIC MYELOID LEUKEMIA
✓ In 90% to 95% of patients with CML, a section of
deoxyribonucleic acid (DNA) is missing from chromosome
22 ( the Philadelphia chromosome [PH1]) it is translocated
unto chromosome 9 (Gambacorti-Passerini, Antolini,
Mahon et.al..2011).
✓ The specific location of these changes is on the BCR gene
on chromosome 22 and the ABL gene on chromosome 9.
✓ When these two genes fuse (BCR-ABL) they produce the
abnormal protein ( a tyrosine kinase protein) that cause
leukocytes to divide rapidly.
 CHRONIC MYELOID LEUKEMIA
✓ CML accounts for 10% to 15% of all leukemias; it is
uncommon in people younger than 20 year; the incidence
increases with age (mean age is 65 years)
✓ Due to marked advances in treatment, patients diagnosed
with CML in the chronic stage have an overall median life
expectancy well exceeding 5 years; in one multicenter
study, those patients who were in complete cytogenetic
remission from treatment had no difference in survival
compared to the general population.
 CLINICAL MANIFESTATIONS
✓The clinical picture of CML varies. Patients may be
asymptomatic, and leukocytosis is detected by a CBC
performed for some other reason. The leukocyte count
commonly exceeds 100,000/mm3.
✓Patients with extremely high leukocyte counts may be
short to breathe or slightly confused because of
decreased perfusion to the lungs and brain from
leukostasis (the excessive volume of leukocytes
inhibits blood flow through the capillaries) .
 CLINICAL MANIFESTATIONS
• enlarged , tender spleen , and
• may also enlarged and tender spleen; and
• liver may also be enlarged and tender.
• Some patients have insidious symptoms such as
malaise anorexia , and weight loss.
• Lymphadenopathy is rare.
• There are three stages in CML;
1.chronic transformation and
2. accelerated or
3. blast crisis. Patients develop more symptoms and
complications as the disease progresses.
 MEDICAL MANAGEMENT
➢ An oral formulation of a tyrosine kinase inhibitor,
imatinib mesylate (Gleevec), works by blocking signals
within the leukemia cells that express the protein, thus
preventing a series of chemical reactions that cause the
cell to grow and divide.

➢ Imatinib therapy appears to be most useful in the chronic

phase of the illness. It can induce complete remission at
the cellular and even molecular level.
 MEDICAL MANAGEMENT
➢ Imatinib is metabolized by the cytochrome P450
pathway, which means that drug-drug
interactions are common. In particular, antacids
and grapefruit juice may limit drug
absorption, and large doses of
acetaminophen can cause hepatoxicity.
➢ Other tyrosine kinase inhibitors (dasatinib
[Sprycel] or nilotinib [Tasignal]) are also approved
for primary therapy; each has a slightly (but
importantly) different toxicity profile.
 MEDICAL MANAGEMENT
➢ Dasatinib is very myelosuppressive and shows a
significant risk for pleural effusion and for causing a
prolonged QT interval;
➢ Nilotinib has more cardiotoxic effects, including
dysrhythmias and risk for sudden death.
➢ In those instances where Imatinib (at conventional doses)
does not elicit a molecular remission, or when the
remission is not maintained, other treatment options may
be considered the dosage of imatinib can be increased
with (increased toxicity) or another inhibitor of BCR-ABL
(e., g dasatinib or nilotinib) or HSCT can be used.
 MEDICAL MANAGEMENT
➢ CML is a disease that can potentially be cured
with each HSCT in otherwise healthy patients
who are younger than 65 years.
➢ However, with the development of tyrosine
kinase inhibitors, the timing of transplant has
come into question.
➢ Patients who receive such transplants while still
in the chronic phase of the illness tend to have a
greater chance of cure than those who received
them in the acute phase.
 MEDICAL MANAGEMENT
➢ The transformation phase can be insidious or rapid; it
marks the process of evolution (or transformation) to the
acute form of leukemia (blast crisis). In the transformation
phase the patient may complain of bone pain and may
report fevers (without any obvious sign of infection) and
weight loss.
➢ Even with chemotherapy, the spleen may continue to
enlarge. The patient may become more anemic and
thrombocytopenic; an increased basophil level is detected
by the CBC.
 MEDICAL MANAGEMENT
• In the acute form of CML (blast crisis), treatment
may resemble induction therapy for acute
leukemia using the same medications as for AML
or acute lymphocytic leukemia .
• Patients whose disease evolves into
“lymphoid” blast crisis are more likely to be able to
reenter a chronic phase after induction therapy.
• For those whose disease evolves into AML,
therapy has been largely effective in achieving a
second chronic phase.
 MEDICAL MANAGEMENT
➢ In rare instances when a purely palliative approach is
desired, the therapeutic approach focuses on reducing
the leukocyte count to a more normal level but does not
alter cytogenetic changes.
➢ This goal can be achieved by using oral
chemotherapeutic agents typically hydroxyurea or
busulfan (Myleran) In the case of an extreme
leukocytosis at diagnosis (e.,g., leukocyte count greater
than 300 000 /mm3), a more emergent treatment may
be required.
 MEDICAL MANAGEMENT
➢ In this instance leakapheresis ( in which the patient's
blood is removed and separated, with the leukocytes
withdrawn and the remaining blood returned to the
patient) can temporarily reduce the number of
leukocytes.
➢ An anthracycline chemotherapy agent ( e.,g.,
daunorubicin [Cerubidine]) may also be used to bring the
leukocyte count down quickly to a safer level where
more conservative therapy can be instituted.
 NURSING MANAGEMENT
▪ Advances in treatment of CML have changed the
trajectory of the disease, from life-threatening and likely
fatal to being a chronic illness. Nurses need to
understand that the effectiveness of the drugs used to
treat CMLl is based on the ability of the patient to adhere
to the medication regimen as prescribed. For example,
one study found that response to treatment was not
achieved when adherence to taking the medication was
less than 80% (MArtin, Bazeos, MAhon, et. al., 2010).
 NURSING MANAGEMENT
➢ Patients were found to both unintentionally and
intentionally not adhere to their medication regimen,
from respectively either forgetting to take a dose or due
to side effects of the medication (Eliasson, Clifford,
Barber et.,al., 2011).
➢ Most patients were not informed of the consequences
of not taking their medication and did not perceive
missing doses as jeopardizing the efficacy of treatment.
 NURSING MANAGEMENT
➢ This highlights the importance of nurses educating
patients and assisting them to identify methods that help
them remember to take their medication, to manage side
effects, and to obtain prescription renewals on time.
➢ Nurses must encourage patients to raise issues of
concern that interfere with their adherence to their
prescribed therapy.
 ACUTE LYMPHOCYTIC LEUKEMIA
➢ ALL results from an uncontrolled proliferation of immature
cells (lymphoblas) derived from a lymphoid stem cell. The
cell of origin is the precursor to the B lymphocyte in
approximately 75% of ALL cases T-lymphocyte ALL occurs
in approximately 25% of cases.
➢ The BCR-ABL translocation is found in 20% of ALLl blast
cells .ALL is most common in young children , with boys
affected more often than girls; the peak incidence is four
years of age.
 ACUTE LYMPHOCYTIC LEUKEMIA
➢ After 15 years of age it is relatively uncommon, until age
50 when the incidence again rises. ALL is very responsive
to treatment; complete remission rates are approximately
85% for adults (ACS, 2010a).
➢ Increasing age appears to be associated with diminished
survival the 5-year event-free survival rate is more than
80% for children with ALL but drops to 35% for adults
between 20 and 49 years of age and to 25% for adults
between 50 and 64 years of age (NCI 2011).
 CLINICAL MANIFESTATIONS
➢ Immature lymphocytes proliferate in the marrow and
impede the development of normal myeloid cells.
➢ As a result normal hematopoiesis is inhibited, resulting
in reduced numbers of granulocytes erythrocytes and
platelets.
➢ Leukocyte counts may be either low or high, but there
always is a high proportion of immature cells
 CLINICAL MANIFESTATIONS

➢ Manifestations and leukemic cell infiltration into

other organs are more common with ALL than
with other form of leukemia and include pain from
an enlarged liver or spleen and bone pain.
➢ The CNS is frequently a site for leukemic cells;
thus patients may exhibit cranial nerve palsies or
headache and vomiting because of meningeal
involvement.
 MEDICAL MANAGEMENT
➢ The goal of treatment is to obtain remission without excess
toxicity and with a rapid hematologic recovery so that
additional therapy can be administered if needed.
➢ Due to the heterogeneity of the disease, treatment plans
are based on genetic markers of the disease as well as
risk factors of the patient, primarily age.
➢ Because ALL frequently invades the CNS, preventive
intrathecal chemotherapy is also a key part of the
treatment plan. Cranial irradiation is frequently used as a
preventive measures .
 MEDICAL MANAGEMENT
➢ Treatment protocols for all tend to be complex , using a
wide variety of chemotherapeutic agents and complicated
administration schedules . The expected outcome of
treatment is complete remission.
➢ Lymphoid blast cells are typically very sensitive to
corticosteroids and vinca alkaloids; therefore, these
medications are an integral part of the initial induction
therapy.
➢ The corticosteroid dexamethasone is preferred to
prednisone as it is more toxic to lymphoid cells and has
better CNS penetration (Bassan and Hoelzer, 2011).
 MEDICAL MANAGEMENT
➢ Typically an anthracycline is included, sometimes with
asparaginase (Elspar) .
➢ Once a patient is in remission special testing
(immunophenotyping immunoglobulin gene
rearrangements T-cell receptor genes, molecular testing) is
done to look for residual leukemia cells; these test can
detect as little as one ALL cell among 10,000 to 100,000
normal cells.
➢ This minimal residual disease testing is useful as a
prognostic indicator.
 MEDICAL MANAGEMENT
▪ In the adult with the role of hsct is controversial,
however, when feasible HSCT may be used for
intensification therapy.
▪ Transplantation can improve long-term disease-free
survival, although the risk of death or long-term morbidity
associated with procedure.
▪ More frequently transplantation is reserved for patients
whose disease relapses after chemotherapy or those who
high risk for relapse.
▪ Despite its complexity, treatment can be provided in the
outpatient setting in some circumstances until severe
complications develop.
 MEDICAL MANAGEMENT
▪ Tyrsine kinase inhibitors (ex. imatinib) appear effective in
patients with PH + ALL; these can be used alone or in
combination with conventional therapy
▪ Monoclonal antibodies, in which the antibody is specific to
the antigen expressed on the ALL blast cell is selected for
treatment are also under the study (Bassan and Hoelzer,
2011)
▪ Patients with ALLl can experience some unique adverse
effects from treatment. The use of corticosteroids to treat
ALL increases the patient's susceptibility to infection; viral
infections are common.
 MEDICAL MANAGEMENT
• Avascular necrosis can occur in patients treated with
corticosteroid-based chemotherapy, as well as that will
transplantation.
• Patients treated with asparaginase are at increased risk for
thrombosis.
• Hepatic toxicity is also common and may necessitate
cessation of supportive drugs, such as proton pump
inhibitors and certain antibacterial and antifungal drugs.
 CHRONIC LYMPHOCYTIC
LEUKEMIA
• CLL is a common malignancy of older adults the average
age at diagnosis is 72 years (ACS 2010b).
• CLL is the most common form of leukemia and the United
States and Europe, affecting more than 120,000 people.
• A family history of CLL may be the most important risk
factor for developing the disease (Lanasa, 2010).
• Veterans of the Vietnam war who were exposed to Agent
Orange may be at risk for developing this disease, but
there is no definitive link to other pesticides or chemical
exposures
 PATHOPHYSIOLOGY
▪ CLL is typically derived from a malignant clone of
B-lymphocytes (T-lymphocytes CLL is rare).
▪ In contrast to the acute forms of leukemia most
leukemia cells in CLL are fully mature.
▪ One possible mechanism that can explain this
oncogenesis is that these cells can escape
apoptosis (programmed cell death), resulting in
an excessive accumulation of the cells in the
marrow and circulation .
 PATHOPHYSIOLOGY
• The disease is classified into three or four stages (two
classification systems are in use). In the early stage an
elevated lymphocyte count is seen; it can exceed 100
000/mm3.
• Because the lymphocytes are small they can easily travel
through the small capillaries within the circulation, and the
pulmonary and cerebral complications of leukocytosis (as
seen with myeloid leukemias) are not typically found in
CLL.)
 PATHOPHYSIOLOGY
• More sophisticated prognostic markers ( e.,g., test that
goes the overall prognosis) are now used for patients with
CLL. Beta-2 microglobulin, a protein found on the surface
of lymphocytes can be measured in the serum; an elevated
level correlates with more advanced clinical stage and
poorer prognosis.
• Immunophenotyping does not only helps establish the
diagnosis but also the prognosis; other special cytogenetic
analysis (e.,g., fluorescence in situ hybridization [FISH])
also used to guide prognosis and therapy.
 PATHOPHYSIOLOGY
• Autoimmune complications can occur at any
stage, as either autoimmune hemolytic anemia or
idiopathic thrombocytopenic purpura.
• In the autoimmune process, the
reticuloendothelial system destroys the body’s
own erythrocytes or platelets.
• Patients with CLL also have a greater risk for
developing other cancers typically, bone, lung, and
skin.
 PATHOPHYSIOLOGY
▪ Roughly 10% of patients will experience a gradual
transformation of their disease to one that becomes
refractory to chemotherapy( prolymphocytoid
transformation)
▪ Slightly fewer patients will experience a sudden
transformation to a very aggressive lymphoma (Ritcher’s
transformation) markedly increase lymphadenopathy
splenomegaly worsening B symptoms (fever night sweats
weight loss) , with average survival only six months.
 CLINICAL MANIFESTATIONS
• Many patients are asymptomatic and are diagnosed
incidentally during routine physical examinations or during
treatment for another disease.
• An increased lymphocyte count (lymphocytosis) is always
present. The erythrocyte and platelet counts may be
normal or, in later stages of the illness, decreased.
• Enlargement of lymph nodes lymphadenopathy is
common; this can be severe and sometimes painful, the
spleen can also be enlarged splenomegaly.
 CLINICAL MANIFESTATIONS
• The patients with CLL can develop a constellation
of symptoms including fever drenching sweats
(especially at night0 and unintentional weight
loss. T-cell function is impaired and may be the
cause of tumor progression and increased
susceptibility to second malignancies and
infections.
 CLINICAL MANIFESTATIONS
• Life-threatening infections are particularly common
with advanced disease. Viral infections such as
herpes-zoster can become widely disseminated.
Defects in the complement system are also seen,
which results in increased risk of developing
infection with encapsulated organisms
 MEDICAL MANAGEMENT
• A major paradigm shift has occurred in CLL
therapy
• in the past, there appeared to be no survival
advantage in treating CLL in its early stages
however with the advent of newer treatment
modalities and more sensitive means of
determining prognosis, achieving complete
remission and eradicating even minimal or
residual disease results in improved survival.
 MEDICAL MANAGEMENT
➢The chemotherapy agents blood fludarabine
(Fludara) and cyclophosphamide (Cytoxan) are
often given in combination with the monoclonal
antibody rituximab (Rituxan) The major side effect
of fluradarabine is a prolonged bone marrow
suppression manifested by prolonged periods of
neutropenia, lymphopenia and thrombocytopenia
which puts patients at risk for such infections
as Pneumocystis jiroveci, Listeria, mycobacteria,
herpes viruses and cytomegalovirus
 MEDICAL MANAGEMENT

➢ Another alkylating agent bendamustine (Trenda) is also

effective, particularly when combined with rituximab
(Gibben and O’Brien, 2011)
➢ The monoclonal antibody alemtuzumab (Campath) is often
used in the combination with other chemotherapeutic
agents when the disease is refractory to fludarabine, the
patient has a very poor prognostic marker, or it is
necessary to eradicate residual disease after initial
treatment
 MEDICAL MANAGEMENT

• Alemtuzumab targets the CD52 antigen commonly found in

CLL cells, and it is effective and clearing the marrow and
circulation of the cells without affecting the stem cells.
• Bacterial infections are common in patients with CLL and
intravenous treatment with immunoglobulin may be given
to selected patients with recurrent infection.
• The role of HCST is unclear due to the older age of was
common patients with CLL transplantation may not be an
option particularly if significant comorbidities exist.