ACUTE MONOCYTIC LEUKEMIA AND

ACUTE LMPHOCYTIC LEUKEMIA OCCURRENCE

DEFINITION ACUTE LYMPHOCYTIC LEUKEMIA

Two Forms:
ACUTE MONOCYTIC ANEMIA FAB M5a
 Pure monocytic leukemia is rare, accounting for • is most common in young adults (median
less than 15% of all leukemias. There are two types age, 16 years)
of FAB M5: FAB M5a and FAB M5b. Acute • The male:female ratio is about 0.7:1 in the
monoblastic leukemia (FAB M5a) and acute M5A form
monocytic leukemia (FAB M5b) are the WHO - The hypercellular marrow of this subtype includes
synonyms. More than 80% of monocytic cells in a large number of large monoblasts with basophilic
AML-M5a are monoblasts, while less than 80% of cytoplasm and delicate azurophilic granules but
monocytic cells in AML-M5b are monoblasts. Acute little to no Auer rods.
monocytic leukemia, also known as AML-5 or M5,
is a subtype of acute myeloid leukemia (AML). FAB M5b
Hyperleukocytosis, coagulation abnormalities, and • has a peak occur- rence characteristically
extramedullary involvement are all associated with during middle age (median age, 49 years).
this subtype of AML, which has distinct clinical and • The male:female ratiois about 1.8:1 in the
biological characteristics. M5B form.
 Acute monocytic leukemia (AMoL, or AML-M5) is - This subtype of leukemia is characterized by
considered a type of acute myeloid leukemia promonocytes with less basophilic cytoplasm and
(AML). In order to fulfill World Health Organization more azurophilic granules. Erythrophagocytosis is
(WHO) criteria for AML-M5, a patient must have normal in these cells, which have folded nuclei with
greater than 20% blasts in the bone marrow, and fine chromatin.
of these, greater than 80% must be of the
monocytic lineage. A further subclassification (M5a
versus M5b) is made depending on whether the ACUTE LYMPHOCYTIC LEUKEMIA
monocytic cells are predominantly monoblasts  The most common cancer in children is ALL, which
(>80%) (acute monoblastic leukemia) or a mixture accounts for 23% of cancer diagnoses in children
of monoblasts and promonocytes (<80% blasts). under the age of 15. Every year, it affects around
one out of every 29,000 children in the United
States. ALL has a bimodal age distribution, peaking
ACUTE LYMPHOCYTIC ANEMIA in children aged 3 to 5 years old and then declining
 Acute lymphocytic leukemia (ALL) is a blood and in people aged 65 and up. Pediatric ALL occurs
bone marrow cancer, the spongy tissue within the slightly more often in boys than in girls and in white
bones where blood cells are made.The term children more often than in black children.
"acute" derives from the fact that acute
lymphocytic leukemia develops quickly and
produces immature blood cells rather than mature
ones. Acute lymphocytic leukemia (ALL) is also ETIOLOGY AND PATHOGENESIS
called acute lymphoblastic leukemia. “Acute”
means that the leukemia can progress quickly, and ACUTE MONOCYTIC LEUKEMIA
if not treated, would probably be fatal within a few  AML may be caused by a variety of congenital and
months. "Lymphocytic" means it develops from acquired conditions.
early (immature) forms of lymphocytes, a type of  The Confenital Predisposing factors are:
white blood cell. • Bloom Syndrome
 All begins in the bone marrow (the soft inner part
• Down Syndrome
of certain bones, where new blood cells are made).
• Twin with Leukemia
Leukemia cells typically enter the bloodstream
• Ataxia Teleangiectasia
easily. They can also spread to other organs such as
• Neurofibromatosis type 1
the lymph nodes, liver, spleen, central nervous
system (brain and spinal cord), and testicles (in • Li-Fraumeni Syndrome
males). Some cancers can start in these organs and • Klinfelters Syndrome
then spread throughout the body.
Acquired Predisposing factors include: in multiple cell lineages in acute myeloid leukemia
• Aplastic Anemia (AML) and Philadelphia chromosome–positive
• Prenatal exposure to tobacco, marijuana and ALL, indicating that they may occur at an earlier
alcohol stage of blood cell growth. Many of the described
• Pesticides, Herbecides,, Benzene, Petroleum molecular mutations bear evidence of
• Myelodysplastic Syndrome immunoglobulin joining region (VDJ) and T-cell
• Radiation receptor (TcR) recombinase activity. A higher risk
• Chemotherapy of leukaemia has been linked to a number of
congenital disorders. Children with trisomy 21
 AML is caused by mutations in the DNA that (Down syndrome) are up to 15 times more likely
regulates cell growth in the bone marrow. If you than average children to experience leukemia.
have AML, the bone marrow contains a significant Some chromosomal defects that are less common
number of immature WBCs. These irregular cells have been related to leukemia. Klinefelter's
ultimately grow into myeloblasts, which are disease, Bloom syndrome, and Fanconi's anemia
leukemic WBCs. These abnormal cells proliferate are among them.
and gradually supplant healthy cells. Your bone
marrow stops working properly as a result, making  Patients with ataxia-telangiectasia (AT), an
your body more vulnerable to infections. The exact autosomal recessive condition marked by
cause of the DNA mutation is unknown. Some increased chromosomal fragility, have been
physicians say it has something to do with shown to have lymphoid malignancies with a
exposure to certain chemicals, radiation, and even predominance of T-ALL. The majority of These
chemotherapy medications. cases have chromosomal and genetic defects
 A DNA mutation in the stem cells in your bone (described in Conventional cytogenetics and
marrow that produce red blood cells, platelets, and molecular genetics). Many of these molecular
infection-fighting white blood cells causes acute changes occur at the location of immunoglobulin,
monocytic leukaemia (AML). Because of the TCR, and transcription factor encoding genes. In
mutation, the stem cells generate much more addition to chromosomal translocations, there is
white blood cells than are necessary. The white a variety of genetic events that appear to be
blood cells produced are still immature, so they do leukemogenic but are undetectable with classic
not have the infection-fighting properties of fully cytogenetic methods. Other gene expression
developed white blood cells. As the number of modalities are beginning to be used to
immature cells increases, the amount of healthy characterize leukaemia. Complementary DNA
red blood cells and platelets decrease, and it's this (cDNA) microarrays, real-time and other
fall that causes many of the symptoms of modifications of reverse transcriptase-
leukaemia. polymerase chain reaction (RT-PCR), which
analyze messenger RNA expression levels, and
new mass spectroscopy techniques for proteins
ACUTE LYMPHOCYTIC LEUKEMIA are among them (proteomics). Researchers may
 The majority of cases display chromosomal and now analyze broad patterns of gene expression at
genetic defects, which arise naturally in genes the RNA or protein level using these and other
that regulate the lymphoid cell population. The t new techniques.
(12;21) translocation, which is the most common
ALL translocation, appears to have favorable
prognostic implications. T (12;21) is a type of
chromosomal abnormality in which a
chromosome breaks and a portion of it reattaches
to a different chromosome.

 A single damaged progenitor cell, capable of

(theoretically) limitless self-renewal, gives rise to
malignant, poorly differentiated precursors in
most cases of ALL, as in other lymphoid
malignancies. It's unclear when the "clonal case"
in leukemia happens in the normal course of
differentiation. There is evidence that these
events occur in committed lymphoid precursors in
pediatric ALL, while there is evidence of mutation
CLINICAL SIGNS AND SYMPTOMS
ACUTE MONOCYTIC LEUKEMIA & ACUTE
LYMPHOCYTIC LEUKEMIA

and smudge cells. The blast types have one or

LABORATORY FINDINGS two nucleoli in the nucleus, and Auer rods are
absent from the cytoplasm.
ACUTE MONOCYTIC LEUKEMIA
 The nuclear-cytoplasmic ratio in these blasts is very
 Anemia and thrombocytopenia are normal in
high. And the nuclear-cytoplasmic ratio is a better
this form of acute leukemia, as they are in
prediction of malignancy.
other types. The total leukocyte count can be
anywhere between 15 to 100 109/L. A high
proportion of blast types is found in peripheral
blood smears.
 Monocytes and promonocytes account for 25 DIAGNOSIS
to 75 percent of the nucleated cells. Blasts
frequently have a muddy or smoggy gray-blue ACUTE MONOCYTIC LEUKEMIA
cytoplasm containing tiny granules, and  The diagnosis of M5 (acute monocytic or
pseudopods are common. monoblastic leukemia) was established as follows:
 The nucleus contains one to five large nucleoli  80% of the leukemic cells are
and has a reticular granular chromatin pattern. morphologically of monocytic lineage,
Occasionally, a few immature erythrocytes will including monoblasts, promonocytes, and
be visible. monocytes; A small granulocytic component
(less than 20%) may be present. And the
ACUTE LYMPHOCYTIC LEUKEMIA number of monoblasts in FAB M5a is about
 The overall leukocyte count is elevated in 60 80%; in FAB M5b, the majority of the
percent to 70 percent of patients, with total monocytic cells are promonocytes (blasts <
leukocyte counts ranging from 50 to 100 × 109/L. 80%.
Less than 15 percent of patients have severe  To distinguish acute monobalstic leukemia
leukocytosis with a total leukocyte count of more the majority of the monocytic cells are 80%
than 100 × 109/L. Just around a quarter of all monoblast, whereas in acute lymphocytic
patients have leukocytopenia. leukemia, the majority of monocytic cells are
 Peripheral blood smears show a predomi- nance of promonocytes.
blast cells. In addition to blasts, the peripheral
blood is usually composed of close to 100 percent
lymphoblasts, lymphocytes,
ACUTE LYMPHOCYTIC LEUKEMIA Usually, 4-6 courses of multidrug chemotherapy
are offered at 3-4 week intervals in most
Blood Test chemotherapy protocols. A high dose and time-
 Blood tests can show an abnormally high or low intensity can have a positive impact on the
number of white blood cells, insufficient red blood treatment's outcome. Intrathecally administered
cells, or insufficient platelets. Blast cells, which are chemotherapy is also used to treat or avoid CNS-
immature cells contained in the bone marrow, can leukemia.
also be detected by a blood test.
Common Drugs to Treat AML:
Bone marrow review • Cytarabine
 A needle is used to extract a sample of bone • Anthracyclins (Daunirubicin, Idarubicin, and
marrow from the hipbone or breastbone during mitoxantrone)
bone marrow aspiration and biopsy. The sample is • Etoposide
sent to a laboratory for testing to see if there are  Each course causes extreme bone marrow
any leukemia cells present. Blood cells can be suppression for a short time, resulting in anemia,
categorized into unique categories by lab doctors leukocytopenia, neutropenia, and
based on their size, shape, and other genetic or thrombocytopenia. This is often followed by life-
molecular characteristics. They also search for threatening (opportunistic) bacterial or fungal
specific variations in cancer cells to see whether infections. Furthermore, chemotherapy
the leukemia cells originated from B lymphocytes treatments cause mucositis, which is caused by the
or T lymphocytes. This knowledge aids in the chemotherapy's cytotoxic impact on the intestinal
creation of a care plan by your doctor. epithelium, necessitating a variety of supportive
care steps. The repeated administration of
Imaging Test. anthracyclins can trigger a short-term (months)
 An X-ray, a computerized tomography (CT) scan, or and long-term decrease in cardiac contractility
an ultrasound scan can both be used to see (years).
whether cancer has spread to the brain and spinal
cord, as well as other areas of the body. ACUTE LYMPHOCYTIC LEUKEMIA
 For Philadelphia (Ph) chromo-some positive and
Spinal Fluid Test negative ALL, treatment regimens vary. A
 A lumbar puncture test, also known as a spinal tap, reciprocal translocation between chromosomes 9
is a procedure that collects a sample of the spinal and 22 gives rise to the Ph chromosome. In terms
fluid, which surrounds the brain and spinal cord. of genetics, this translocation takes upstream
The spinal fluid sample is checked to see whether domains from the BCR gene on chromosome 22
cancer cells have spread to it along with downstream Abl tyrosine kinase
domains on chromosome 9. In cases of Ph
Fluorescent in situ hybridization (FISH): chromosome–positive ALL, first- and second-
 This is another way to look at chromosomes and generation ABL kinase inhibitors have become
genes. It uses special fluorescent dyes that only standard treatment. The addition of imatinib
attach to specific genes or parts of particular mesylate, a bcr-abl tyrosine kinase inhibitor, to the
chromosomes. FISH can find most chromosome hyper-Cytoxan (cyclophosphamide), vincristine,
changes (such as translocations) that are visible adriamycin (doxorubicin), dexamethasone (hyper-
under a microscope in standard cytogenetic tests, CVAD) regimen for adult ALL with t(9;22), improved
as well as some changes too small to be seen with patient results when compared to a regimen
usual cytogenetic testing. without imatinib mesylate.

The addition of imatinib mesylate to:

TREATMENT • Cyclophosphamide
• Vincristine
ACUTE MONOCYTIC LEUKEMIA • Adriamyein (doxorubicin)
 AML is also a daunting disease to treat. Aggressive • Dexamethasone
multidrug chemotherapy regimens are used to
treat the disease, and are associated with
significant mortality and morbidity. These key-
drugs are given repeatedly using different dosing
schemes and may be related to drugs like 6-
thioguanine, dexamethasone, and amsacrin.
COURSE AND PROGNOSIS

ACUTE MONOCYTIC LEUKEMIA

 Modern treatment strategies have resulted in a
high rate of survival in infants, but over the last
three decades, the only substantial improvement
in treatment has been limited to younger patients
rather than the majority of older patients.

ACUTE LYMPHOCYTIC LEUKEMIA

 Acute lymphocytic leukemia can progress quickly if
untreated. However, ALL is one of the most curable
cancers and survival rates are now at an all-time
high.
CHRONIC GRANULOCYTIC LEUKEMIA heralded by an increase in splenomegaly, a
rising peripheral blood leukocyte count, an
increased percentage of basophils, worsening
DEFINITION anemia and thrombocytopenia.
 Chronic Granulocytic Leukemia, also called as
Chronic Myelogenous Leukemia or Chronic Myeloid • Blast Crisis (Acute Phase)
Leukemia, is a multipotential hematopoietic stem  It is characterized by the appearance of
cell disease characterized by anemia, extreme primitive blast cells similar to those seen in
blood granulocytosis and granulocytic immaturity, acute leukemia. It is defined by the presence of
basophilia, often thrombocytosis, and 30% or more leukemic cells in peripheral blood
splenomegaly (Kaushansky, 2016). or marrow or the presence of extramedullary
infiltrates of blast cells.
OCCURRENCE  Exposure to very high doses of ionizing
 CML is predominantly a leukemia of middle-aged radiation can increase the occurrence of CML
adults. The median age at diagnosis is n the fifth above the expected frequency in comparable
and sixth decades of life. Males have slightly populations (Kaushansky, 2016).
greater rate of disease occurrence. The incidence
of CML in Western countries is estimated to be CLINICAL SIGNS AND SYMPTOMS
approximately 2 per 100,000 persons annually and  In the 70 percent of patients who are symptomatic
accounts for 15% of leukemias in adults (all age at diagnosis, the most frequent complaints include
groups included). Five to ten percent of patients easy fatigability, loss of sense of well-being,
have history of excessive radiation exposure. decreased tolerance to exertion, anorexia and
(Turgeon, 2012) abdominal discomfort, early satiety (related to
splenic enlargement), weight loss and excessive
ETIOLOGY AND PREVENTION sweating. The symptoms are vague, nonspecific,
 The majority of CML cases is molecularly defined and gradual in onset (weeks to months). A physical
by the presence of the hallmark Philadelphia examination may detect pallor and splenomegaly.
chromosome (Ph), which is a reciprocal Sternal tenderness, especially the lower portion, is
translocation resulting from the fusion of the common; occasionally, patients notice it
breakpoint cluster region (BCR) gene on 22q11.2 themselves.
and the Abelson murine leukemia (ABL1) gene on  Uncommon presenting symptoms include those of
9q34.1. Thus, t (9;22) (q34.1; q11.2) results in BCR- dramatic hypermetabolism (night sweats, heat
ABL1 fusion product with abnormal tyrosine kinase intolerance, weight loss) simulating thyrotoxicosis;
activity, playing a central role in the abnormal cell acute gouty arthritis, presumably related in part to
proliferation. hyperuricemia; priapism, tinnitus or stupor from
 CML is categorized into three categories: (1) the leukostasis associated with greatly
Chronic Phase CML (CP-CML) which if left exaggerated blood leukocyte count elevations; left
untreated it will eventually progress to (2) upper quadrant and left shoulder pain as a
Accelerated Phase CML (AP-CML) or (3) Blast Phase consequence of splenic infarction and perisplenitis;
CML (BP-CML) in 3 to 5 years; thus, early vasopressin-responsive diabetes insipidus; and
recognition and targeted treatment with novel acne urticate associated with hyperhistaminemia.
tyrosine kinase inhibitors (TKIs) are crucial to
improving patient outcomes and disease-specific
survival. (Sailman, 2017) LABORATORY FINDINGS
• Initial (Chronic) Phase CELL COUNT
 Its onset is insidious and may last from 3 to 5
Tests Normal Values Result
years. Most cases (85%) are diagnosed in this
phase. Splenic infarction on this stage is M: 4.60-6.0 x 1012/L
RBC Count Decreased
common because of the abnormal F: 4.0-5.4 x 1012/L
overproduction and accumulation of M: 14.0-18.0 x 1012/L
Hemoglobin Decreased
granulocyte precursors in the bone marrow, F: 12.0-15.0 x 1012/L
spleen and blood. WBC Count 4.5-5.10 x 1012/L Increased
• Accelerated Phase Platelet Count 150-450 x 1012/L Decreased
 A transitional, accelerated period may precede
blast transformation. This transition is
LEUKOCYTE DIFFERENTIAL COUNT o Large focci or clusters of blasts in the bone
marrow biopsy
Types of Cell Normal Value Result • Complete Blood Count. When the CML is more
Basophils 0-2% Increased advanced, there may be also be low levels of red
blood cells, a condition called anemia, and either
PMNs 50-70% Increased
high or low numbers of platelets
Bands 0-5% Increased
• Bone Marrow Biopsy
Lymphocyte 18-42% Normal
• Fluorescence in Situ Hybridization (FISH). A test
Monocyte 2-11% Increased
used to detect the BCR-ABL1 gene and to monitor
Eosinophils 1-3% Increased
the disease during treatment.
• Polymerase Chain Reaction (PCR). A highly
sensitive test that can be sued to look for the BCR-
BONE MARROW BIOPSY ABL1 oncogene in leukemia cells.
• Leukocyte Alkaline Phosphatase (LAP) Test which
Cellularity Increased is useful for preliminary differentiation of CML
Granulopoiesis Increased from a leukomoid reaction. (A leukomoid reaction
Erythropoeisis Decreased is produced by a severe infection or inflammation
Megakaryopoiesis Increased and frequently resembles leukemia on bone
marrow or blood smears.

LEUKOCYTE ALKALINE PHOSPHATASE (LAP) TEST

TREATMENT
Condition LAP Score
CML Decreased • Imatinib mesylate (Imatinib) is a selective inhibitor
Leukemoid Reaction Increased of the BCR-ABL TK, which occupies the ATP-binding
site of several TK molecules (bcr-abl oncoprotein)
and prevents phosphorylation of substrates that
DIAGNOSIS are involved in regulating the cell cycle. The TKs are
 2016 World Health Organization (WHO) ABL, BCR/ABL, AARG, PDGF-R α and β, and c-KIT. It
Diagnostic Categories of CML, BCR-ABL1 Positive: is recommended as the best single agent for newly
• CP-CML: Not meeting the two criteria described as diagnosed patients who are not eligible for initial
follows: treatment by allogeneic stem cell transplantation.
• AP-CML: • Interferon Alpha (IFN-α) improves the frequency
o Hematologic/Cytogenetic Criteria: and duration of hematologic remission and
 Blasts 10% t0 19% of white blood cells reduces the frequency of Philadelphia
(WBCs) in peripheral and/or nucleated chromosome.
bone marrow cells • Bone Marrow Transplantation. Treatment
 Peripheral blood basophils ≥20% requires chemotherapy followed by
 Persistent thrombocytopenia (<100 x transplantation of mobilized normal progenitor
109/L) unrelated to therapy, or persistent cells. Bone marrow transplants are more successful
thrombocytosis (>1000 x109/L) in patients up to age 55.
unresponsive to therapy • Dasatinib and Nilotinib which are recommended
 Cytogenetic evidence of clonal evolution for chronic phase of CML.
o “Provisional” response-to-TKI criteria: o Disatinib is a second-generation oral BCR-
 Hematologic resistance to the first (or ABL1 inhibitor with dual inhibition of ABL1
failure to achieve a complete hematologic and SRC. It can bind to both the active and
response to the first TKI) OR inactive conformation of theABL1 kinase
 Any hematological, cytogenetic, or domain, so it may be affected by mutations
molecular indications of resistance to two resulting in resistance.
sequential TKIs OR o Nilotinib is a selective, orally bioavailable,
 Occurrence of two or more mutations in ATP-competitive inhibitor of BCR-ABL1
BCR-ABL1 during TKI therapy which is 20 to 50 times more potent than
• BP-CML imatinib in vitro.
o Blasts ≥20% of peripheral WBC or of nucleated
bone marrow cells
o Extramedullary blast proliferation
COURSE AND PROGNOSIS
• For patients treated initially with imatinib, BCR-
ABL1 expression in cytogenetic responders and
nonresponders was similar. BCR-ABL1 expression
became significantly different 3 months after
treatment and became increasingly different
between responders and nonresponders with
continued therapy at 6, 9 and 12 months.
• In patients receiving second-generation TKIs as
second-line therapy, those who have no cytogenic
response at 3 to 6 months should be considered for
allogenic transplantation or switched to an
alternative therapy in a clinical trial.
• With the advent of TKI treatment, median survival
in chronic phase CML is estimated to be 25 to 30
years. The prevalence of CML in the TKI era is
estimated to reach a plateau 35 times the annual
incidence with plateau estimated to occur in 2050.
 CHRONIC MONOCYTIC LEUKEMIA liver and spleen, causing them to enlarge. They can
cause also the bone marrow to make less of the
other blood cells
Definition • Spelenomegaly
 Chronic myelomonocytic leukemia (CMML) is a • Infection
type of cancer that starts in blood-forming cells of • Hepatomegaly
the bone marrow and invades the blood. It  Having too many monocytes also causes many of
happens when monocytes in the bone marrow the symptoms of CMML. These monocytes can
begin to grow out of control, filling the bone settle in the spleen or liver, enlarging these organs.
marrow and preventing other blood cells from An enlarged spleen called splenomegaly, it can
growing. cause pain in the upper left part of the belly
 CMML is a type of diseases in which uncontrolled (abdomen). It can also cause people to notice they
neoplastic stem cell proliferation leads to feel full too fast when they eat. If the liver gets too
elevations in monocyte and decreases in blood and big this is called hepatomegaly, it causes
platelet production. discomfort in the upper right part of the abdomen.
Low numbers of other types of blood cells cause
Occurrence many of the signs and symptoms of CMML. Not
 CMML is rare occurring in about 4 of every 1 million having enough normal white blood cells
people in the U.S. each year, with about 1,100 new (leukopenia) can lead to frequent or severe
cases diagnosed annually. About 9 out 10 cases are infections
found in people 60 and older. CMML occurs more
often in men than in women and is very rare in
young people Diagnosis
 About half of all patients have a form of CMML in • Blood Test
which there is a high white cell count at diagnosis • CBC
and the condition behave like myeloproliferative  People with CMML have higher numbers of
neoplasm or MPN and the other half have normal monocytes, (at least 1,000 cu.mm.). Sometimes
or reduced white cell count at diagnosis and they have low numbers of other white blood cells.
behaves more like myelodysplastic syndrome or They may have shortages of red blood cells and
MDS blood platelets, as well. Blood cells from CMML
patients may also have certain changes in size,
shape, or other features that can be seen under the
Etiology and Pathogenesis microscope. Blood abnormalities may suggest
 The primary cause of CMML is still unknown. There CMML, but an exact diagnosis cannot be made
are however, known risk factors that may increase without looking at and testing cells taken from the
the chances of having CMML. They include. bone marrow.
• Older age
• Being male  Measuring blast
• Exposed to radiation - For a diagnosis of CMML, there must be less than
• Past treatment of certain anticancer drugs 20% blasts in the bone marrow. A patient who has
• Being exposed to certain chemicals at work or in more than 20% blasts in the bone marrow has
the environment acute leukemia.
 Repeated exposure to the chemical benzene can
damage the DNA of normal stem cells. Benzene can  Cytogenetic tests
be found in cigarette smoke and is now the most - CMML cells may also have extra copies of all or part
common known cause of exposure to this toxin. of some chromosomes. Chromosome
This may be the reason why most of the patients translocations may also be seen.
are males, because of smoking cigarette for almost
a long time and, and starts to damage their stem
cells and later diagnosed with CMML Treatment
 Treatment of CMML depends on how severe the
disease is, the age of the patient and health
Clinical Signs and Symptoms • Chemotherapy to kill cancer cells using
 The most common sign of chronic myelomonocytic cytotoxic agents
leukemia is having too many monocytes, a type of • Supportive care with blood transfusion,
white blood cell in the blood, these will settle in the growth factors and antibiotics to treat
 symptoms by increasing blood counts and
stopping infections.
• Stem cell transplant which replaces blood
forming stem cells, in your bone marrow with
healthy stem cells
 However, chemo drugs like hypomethylating
agents are usually mild and rarely lead to stopping
treatment. Still these drugs can have some of the
same side effects as regular chemotherapy like,
low blood cell counts which are commonly white
blood cells or platelets.

Course and Prognosis

• Prognosis is poor, with a median overall
survival of 2-3 years
• 15- 30 % of transformation to acute myeloid
leukemia
 CHRONIC LYMPHOCYTIC LEUKEMIA • Weakness
• Feeling tired
• Swollen lymph nodes
DEFINITION • Pain or a sense of "fullness" in the belly
 It is the most common form of leukemia, • Weight loss
commonly caused by a malignant clone of B cells • Chills
and has a distinct phenotype. It affects a group of • Fever
white blood cells, which causes malfunction in
• Night sweats
fighting bacteria and viruses in the body. The
primary disease sites include peripheral blood,
spleen, lymph nodes, and bone marrow.
Advanced signs and symptoms of CLL:
 Can chronic lymphocytic leukemia patients be
 Not enough red blood cells, healthy white blood
classified into different groups?
cells, and blood platelets
 They can be classified into 3 groups. Those that are
 Prone to infections
only mildly affected by the disease and rarely need
treatment; those who initially have an indolent
course but eventually improve and need
treatment; and those who have an active disease LABORATORY FINDINGS
from the time of diagnosis and need treatment.  BLOOD TESTS o Complete blood count and blood
cell exam (peripheral blood smear)
• Flow cytometry
• Other Blood Tests
OCCURRENCE
 Bone Marrow Tests
 Chronic lymphocytic leukemia represents 22-30%
 GENE TESTS o Cytogenetics & Fluorescent in situ
of all leukemia cases with a worldwide incidence
hybridization (FISH)
projected to be between <1 and 5.5 per 100,000
• Molecular tests
people. Patients are on average 65 years old when
 Lymph node biopsy
they are diagnosed, with just 10% to 15% under the
 Lumbar puncture (or spinal tap)
age of 50, and rarely on children. This disease is
slightly more common to occur in males than
females.
DIAGNOSIS
 French American–British classification system
proposed three morphologic types based on the
ETIOLOGY AND PATHOGENESIS proportion of atypical lymphocytes in blood:
 The exact cause of Chronic Lymphocytic Leukemia 1. Typical CLL- more than 90 percent of the
is unknown. There are hereditary and genetic links lymphocytes are small
noted but no environmental risk factor has been 2. CLL–prolymphocytic leukemia- having a dimorphic
found to be predictive for CLL. population of small lymphocytes and
 A whole genome sequencing study reported that prolymphocytes in the peripheral blood, the
CLL mutations can be attributed to 3 key prolymphocyte population constituting more than
mutational processes: 2 types of activation 10% and fewer than 55% of the circulating
induced cytidine deaminase signatures and an lymphocytes.
aging signature, operating at different times 3. Atypical CLL- there is a heterogeneous lymphoid-
throughout CLL evolution. The frequency of CLL cell morphology but the proportion of
progressively increases with age, suggesting that a prolymphocytes is less than 10 percent. It has
persistent exposure to a self- or none self-antigen morphologic, immunophenotypic, and clinical
may also be a predisposing factor. features that distinguish it from typical CLL

- Once the diagnosis is confirmed, the doctor

CLINICAL SIGNS AND SYMPTOMS determines the extent (stage) of your chronic
 People diagnosed with CLL usually have no lymphocytic leukemia. Rai staging system is most
symptoms; it is sometimes discovered in a blood often used for CLL. It consists of three risk groups:
test for an unrelated health condition and a high  Low risk: o lymphocytosis (excess of lymphocytes)
number of lymphocytes is found.  no enlarged lymph nodes or organs
 Even when people with CLL have symptoms,  RBC and platelet count within or near normal
they're often unclear and may be caused by other levels
conditions which includes:
  Intermediate risk (stages 1 and 2): o
lymphocytosis
 enlarged lymph nodes, spleen, or liver
 RBC and platelet count within or near normal
levels
 High risk (stages 3 and 4): o lymphocytosis
 enlarged lymph nodes, spleen, or liver may or
may not be present
 anemia, or low RBC count
 thrombocytopenia, or low platelet count

TREATMENT
 Current treatment possibilities according to
prognostic factors:
1. Early and Stable Disease
 No treatment required
2. Advanced CLL with a Large Tumor Burden and Bone
Marrow Failure
 Chlorambucil (e.g., at a dose of 6 to 8 mg
orally daily; 0.4 to 0.8 mg per kg of body
weight orally every two weeks)
3. Cytopenia due to an Immune Mechanism or
Hypersplenism
 Corticosteroid (cytotoxic agents added
only if there is no response after four to six
hours of treatment)
 Alternative treatments include high-dose
immune globulin, cyclosporine,
splenectomy, and low-dose radiation to
the spleen
4. Treatment of Systemic Complications
 High-dose immune globulin (400 mg per
kilogram intravenously every three weeks)
 New Treatment Approach:
o Purine Analogues
o Transplantation of Hematopoietic
Progenitors
o Biotherapy

COURSE AND PROGNOSIS

 The prognosis of patients with CLL varies widely at
diagnosis. Some patients die rapidly, within 2-3
years of diagnosis, because of complications from
CLL. Most patients live 5-10 years, with an initial
course that is relatively benign but followed by a
terminal, progressive, and resistant phase lasting
1-2 years. During the later phase, morbidity is
considerable, both from the disease and from
complications of therapy. Prognosis depends on
the disease stage at diagnosis as well as the
presence or absence of high-risk markers.