1. By : SHASHIDHARA and
SHASHIKUMAR

2. HEMATOPIESIS

4. LEUKEMIA

5. INTRODUCTION
• Malignant disorders of the haematopoietic stem cell
compartment, characteristically associated with increased
numbers of white blood cells in the bone marrow and/or
peripheral blood
• Incidence is 10/100000 per annum. Males are affected more
frequently than females (acute leukemia 3:2, chronic
lymphocytic leukemia 2:1, chronic myeloid leukemia 1.3:1)
• Acute leukemia occurs at all ages, chronic leukemia occur
mainly in middle and old age

6. HISTORY
• The discovery of leukemia is largely contributed to German physician
Rudolf Ludwig Karl Virchow (1821-1902) and
• English physician, pathologist and physiologist John Hughes Bennett
(1812-1875) as they were the first to observe the disease
• In 1845 Edinburgh pathologist Bennett reported a “case of hypertrophy
of the spleen and liver in which death took place from suppuration of the
blood” in the Edinburgh medical journal.
• Few weeks later Virchow in berlin published a very similar case.
• Bennett thought that the patient had an infection, Virchow suspected
a neoplastic disorder that he soon called white blood disease or
leukemia

7. CLASSIFICATION

8. Myeloid neoplasms
Lymphoid neoplasms
Histiocytic neoplasms

9. MYELOID NEOPLASMS
• Includes neoplasms of myeloid cell lineage
• There are 5 categories
Myeloproliferative disorders
Myeloproliferative/myelodysplastic diseases
Myelodysplastic syndromes (MDS)
Acute myeloid leukemia
Acute biphenotypic leukemia

10. LYMPHOID NEOPLASMS
• Leukemias of lymphoid lineage and lymphomas of B, T or NK cell origin
• Includes B cell neoplasms ( including plasma cell disorders), T cell
neoplasms, NK cell neoplasms and Hodgkin’s disease
HISTIOCYTIC NEOPLASMS
• Neoplastic proliferations of histiocytes in Langerhans cell histiocytisis

11. CONTD….
• In acute leukemia there is proliferation of primitive stem cells leading to
an accumulation of blasts, predominantly in the bone marrow, which
causes bone marrow failure
• In chronic leukemia the malignant clone is able to
differentiate, resulting in an accumulation of more mature cells
• Lymphocytic and lymphoblastic cells are derived from the lymphoid
stem cell (B cells and T cells)
• Myeloid refers to the other lineage, i.e. precursors of red
cells, granulocytes, monocytes and platelets

12. MYELOPROLIFERATIVE
DISORDERS

13. DEFINITION
They are a group of clonal myeloid
neoplasms in which a genetic alteration occurs in a
hematopoietic progenitor cell leading to its
proliferation resulting in an increase in the peripheral
blood white blood cells (WBCs), red blood cells
(RBCs), platelets, or a combination of these cells.

14. GENETIC
MUTATION
Genetic
Mutation
National Cancer Institute

15. CLASSIFICATION
• Chronic myeloid leukemia
• Polycythemia vera
• Essential thrombocythaemia
• Primary myelofibrosis
• Systemic mastocytosis
• Chronic eosinophilic leukemia
• Stem cell leukemia

16. COMMON FEATURES
• Common pathologic feature of the myeloproliferative disorder is the
presence of mutated, constitutively activated tyrosine kinases
• Hematopoietic growth factors act on normal progenitors by binding
to surface receptors and activating tyrosine kinases, which turn on
pathways that promote growth and survival
• Then mutated tyrosine kinase circumvent normal controls and lead to
the growth factor-independent proliferation and survival of marrow
progenitors
• Most myeloproliferative disorders originate from multipotent myeloid
progenitors

17. CONTD…
• Increased proliferative drive in the bone marrow
• Homing of the neoplastic stem cells to secondary
hematopoietic organs, producing extramedullary
hematopoiesis
• Variable transformation to a spent phase characterized by
marrow fibrosis and peripheral blood cytopenias
• Variable transformation to acute leukemia

18. CONTD…
• The diagnosis of leukemia is usually suspected from an
abnormal blood count, often a raised white count, and is
confirmed by examination of the bone marrow
• This includes the morphology of the abnormal cells, analysis
of cell surface markers (immunophenotyping), clone
specific chromosome abnormalities and molecular changes
• The features in the bone marrow not only provide an
accurate diagnosis but also give valuable prognostic
information

19. CHRONIC MYELOID
LEUKEMIA

20. DEFINITION
A clonal expansion of a hematopoietic stem cell
possessing a reciprocal translocation between
chromosome 9 and 22 resulting in head to tail fusion
of the breakpoint cluster region (BCR) gene on
chromosome 22q11 with ABL1 (named after Abelson
murine virus) gene located on chromosome 9q34

21. INTRODUCTION
• Chronic myeloid leukemia (CML) accounts for about 14% of
all leukemia
• It is one of the family of myeloproliferative neoplasms
(MPNs)
• Almost exclusively a disease of adults with the peak of
presentation between 40-60
• Philadelphia chromosome demonstrated
cytogenetically(95%) or molecularly(5%)
• Slowly progressive

22. HISTORY
• The Philadelphia cytogenecists Peter Nowel and David
Hungerford discovered an abnormally small G-group
chromosome that we now call the Philadelphia
chromosome (Ph)
• 13yrs later Janet Rowley recognized that Ph was the product
of a reciprocal translocation between chromosome 9 and
22
• In 1980s the translocation partners were identified as BCR
and ABL, followed by the discovery that unregulated
tyrosine kinase activity is critical to BCR-ABL’s ability to
transform cells

23. EPIDEMIOLOGY
• Incidence
0.2 to 2.0 per 100000 people per year
• Gender
Higher in men than in women (1.3:1)
• Age
Incidence increases slowly with age until the middle
forties there after rises rapidly
Median age is 66yr

25. CONTD…
• Geographic and/or ethnic variations might contribute to
the variability of incidences
• Most of the patients who get admitted medical therapy
studies are 50 to 60yr (median approximately 53yr)
• Patients in bone marrow transplantation studies are even
younger (median age approximately 40yr)

27. RISK FACTORS

28. • IONISING RADIATION
Radiotherapy
Atomic bombing
X-ray
• CYTOTOXIC DRUGS
Alkylating agents
Exposure to benzene
• GENETIC
identical twin of patients
down’s syndrome
• IMMUNOLOGICAL
immune deficiency states

29. ETIOLOGY

30. • CML was the first malignancy to be linked to a clear genetic
abnormality
• Approximately 95% of the patients with CML have a chromosome
abnormality known as the Philadelphia (Ph) chromosome
• This is a shortened chromosome 22 resulting from a reciprocal
translocation of material with chromosome 9
• The break on chromosome 22 occurs at breakpoint cluster region
(BCR)
• The fragment from chromosome 9 carries the abl oncogene which
forms a chimeric gene with the remains of the BCR

32. CONTD…
• This BCR ABL chimeric gene codes for a 210kDa protein with tyrosine
kinase activity
• The chimeric gene is transcribed into a hybrid BCR-ABL1 mRNA in
which exon 1 of ABL1 is replaced by variable numbers of 5’ BCR exons
• Bcr-Abl fusion proteins p210BCR-ABL1 are produced that contain NH2terminal domains of Bcr and COOH-terminal domains of Abl
• A rare breakpoint occurring within 3’ region of the BCR gene yields a
fusion protein of 230 kDa, p230BCR-ABL1
• Bcr-abl fusion protiens can transform hematopoietic progenitor cells in
vitro

34. CONTD…
Attachment of the BCR sequences to ABL1 results in 3
critical functional changes
Abl protein becomes constitutively active as a tyrosine
kinase (TK) enzyme, activating downstream kinases that
prevent apoptosis
The DNA-protein-binding activity of Abl is attenuated; and
The binding of Abl to cytoskeletal actin microfilaments is
enhanced

35. CONTD..
• Chromosomal instability of the malignant clone is a basic
feature of CML
• Heterogeneous structural alterations of the TP53 gene, as
well as structural alterations and lack of protein production
of the retinoblastoma 1 (RB1) gene and the catalytic
component of telomerase, is associated with disease
progression
• Rare patients show alterations in the rat sarcoma viral
oncogene homologue (RAS)

36. CONTD…
• Sporadic reports also document presence of an altered
v-mync myelocytomatosis viral oncogene homologue (MYC)
gene
• Progressive de novo DNA methylation at BCR-ABL1 locus
and hypomethylation of the LINE-1 retrotransposon
promoter promotes blastic transformation
• Interleukin 1β may be involved in the progression of CML to
the blastic phase
• Functional inactivation of the tumour suppressor protein
phosphatase A2

37. CLINICAL FEATURES

38. SYMPTOMS
• Insidious in onset, some are asymptomatic others may
present with fatigue, malaise and weight loss or have
symptoms resulting from splenic enlargement, such as early
satiety and left upper quadrant pain or mass
• Less common features related to granulocyte or platelet
dysfunction are infection, thrombosis or bleeding
• Occasionally leukostatic manifestations due to severe
leukocytosis or thrombosis such as vasoocclusive
disease, CVA, MI, venous thrombosis, priapism, visual
disturbances, pulmonary insufficiency

39. SYMPTOMS AT PRESENTATION
Symptom
Present (%)
Tiredness
Weight loss
Breathlessness
Abdominal pain and discomfort
Lethargy
Anorexia
Sweating
Abdominal fullness
Bruising
Vague ill health
37
26
21
21
13
12
11
10
7
7

41. PROGRESSION OF CML
Characterised by worsening of symptoms
• Unexplained fever
• Significant weight loss
• Increasing dose requirements
• Bone and joint pain
• Bleeding, thrombosis and infection
Less than 10-15% of newly diagnosed patients present with
accelerated disease or with de novo blastic phase CML

42. SIGNS
• Minimal to moderate spenomegaly
• Mild hepatomegaly
• Persistent splenomegaly despite continued
medication is a sign of disease acceleration
• Lymphadenopathy and myeloid sarcomas are
unusual

43. CHRONIC PHASE
• Approximately 85% of the patients with CML are in this phase at the
time of diagnosis
• It is sometimes called the stable phase
• Patients are usually asymptomatic (25 to 60%)
• In symptomatic patients, the most common presenting signs and
symptoms are
Fatigue
Left upper quadrant pain or mass
Weight loss
Palpable spleen in 30 to 70% of patients
Liver is enlarged in 10 to 20%

44. CONTD…
• Patients with very high WBC counts may have
manifestations of hyperviscosity, including
priapism, tinnitus, stupor, visual changes and CVA
• If untreated or treated with drugs that do not significantly
affect the Philadelphia- chromosome cells in the
marrow, chronic phase is associated with a median survival
of 4 to 5 yrs
• In the absence of treatment chronic phase progresses to
this phase

45. ACCELERATED PHASE
• This is an ill-defined transitional phase
• The criteria used in all the studies with interferon and tyrosine
kinase inhibitors include the presence of any one of the
following factors

47. CONTD…
• Cytogenetic evolution with new abnormalities in addition to
Philadelphia chromosome
• The classification used may affect the expected outcome
of a group of patients
• More frequently symptomatic, including fever, night
sweats, weight, progressive splenomegaly
• Accelerated phase indicates that the disease is progressing
and transformation to blast crisis is imminent
• With imatinib therapy 4 yr survival rate exceeds 50%

48. BLAST CRISIS
• This is the final phase in the evolution of CML, behaves like
an acute leukemia with rapid progression and short survival
• It is diagnosed if any of the following is present
 > 20% blasts in the marrow or peripheral blood
 Large clusters of blasts in the bone marrow on biopsy
 Development of chloroma (solid focus of leukemia outside
the bone marrow- CNS, lymph nodes, skin etc)

49. CONTD…
• Recent evidence suggests patients with 20 to 29% blasts
have a significantly better prognosis than those having at
least 30% blasts
• Approximately 70% of these patients have a myeloid
phenotype, 25% have a lymphoid phenotype and 5% have
an undifferentiated phenotype
• Symptoms include weight loss, fever, night sweats, bone
pain
• Anemia, infectious complications and bleeding are
common

50. CONTD…
• Subcutaneous nodules or hemorrhagic tender skin
lesions, lymphadenopathy and signs of CNS
leukemia may be present
• Patients in blastic phase usually die within 3 to 6
months
• Prognosis is slightly better in lymphoid blastic phase

51. HEMATOLOGICAL
FINDINGS

52. • Elevated white blood cell count with increase in both
immature and mature granulocytes
• <5% circulating blasts and <10% blasts and promyelocytes
with majority of cells being myelocytes, metamyelocytes and
band forms
• Elevated platelet counts
• Mild degree of normocytic normochromic anemia
• Leukocyte alkaline phosphatase is low in CML cells
• Basophilia resulting in production of Histamine

54. • Bone marrow cellularity is increased with increased myeloidto-erythroid ratio
• Marrow blast percentage may be normal or slightly elevated
• Marrow or blood basophilia, eosinophilia, and monocytosis
• Collagen fibrosis in the marrow is unusual but reticulin stainmeasured fibrosis are noted in half of the patients

56. DISEASE ACCELERATION
• Increasing degree of anemia unaccounted for by bleeding
• Cytogenitic clonal evolution
• Blood or marrow blasts between 10 and 20%
• Blood or marrow basophils ≥ 20%
• Platelet count <100000/µl

57. • Blast crisis is defined as acute leukemia with blood or
marrow blasts ≥ 20%
• Hypopigmented neutrophils may appear (pelger-huet
anomaly)
• Blast cells can be classified as
myeloid, lymphoid, erythroid, or undifferentiated based on
morphologic, cytochemical and immunologic features

58. PELGER HUET
ANOMALY

59. CHROMOSOMAL
FINDINGS

60. • Hallmark of CML is t(9;22) found in 90-95% of the patients
• Shortened chromosome 22 designated as the Philadelphia
chromosome that arises from the reciprocal t(9;22)
• Some have complex translocations- variant translocations
involving 3,4,5 chromosomes
• Investigations that can be done are
karyotyping, fluorescence in-situ hybridization
(FISH), quantitative RT-PCR

61. KARYOTYPING

62. FISH
Bcr- Ch 22
Abl – Ch 9
Bcr-Abl Fusion

63. MANAGEMENT

64. LABORATORY FINDINGS
I. Blood picture:
a. Anemia- usually of moderate degree and is normocytic
normochromic in type. Occasional normoblasts may be
present.
b. White blood cells-
Marked leucocytosis ( approximately 2,00,000/µl or more at
the time of presentation )
The natural history of CML consists of 3 phaseschronic, accelerated and blastic.

65. 
Chronic phase
- begins as a myeloproliferative disorder and consists of
excessive proliferation of myeloid cells ( mainly myelocytes
and metamyelocytes ) and mature segmented neutrophils.
-Myeloblasts usually do not exceed 10% of cells in the
peripheral blood and bone marrow.
-Increase in basophils upto 10% is a characteristic feature
of CML.
- A rising basophilia is indicative of impending blastic
transformation.

66. 
Accelerated phase
-There is progressively rising leucocytosis
-Associated with thrombocytosis or thrombocytopenia and
spleenomegaly
-Increasing degree of anemia
-Blast count in blood or marrow is b/w 10-20%
-Marrow basophils 20% or more

70. 
Blastic phase or blast crisis
-It resembles the acute leukemia in having blood or
marrow blasts > or =20%.
-These blasts cells may be myeloid, lymphoid, erythroid or
undifferentiated and are established by morphology,
cytochemistry or immunophenotyping.
-Myeloid blast crisis is more common and resembles AML
-However, unlike AML, Auer rods are not seen

72. c. Platelets
-count may be normal but is raised in about half the cases

73. (2) Bone marrow examination
examination of marrow aspiration yields the following
results

Cellularity
-there is hypercellularity with total or partial replacement of
fat spaces by proliferating myeloid cells.

Myeloid cells
-they predominate in the bone marrow with ↑sed M:E ratio
-The differential counts of myeloid cells in the marrow show
similar findings as seen in the peripheral blood with
predominance of myelocytes

74. 
Erythropoiesis
-Is normoblastic but there is reduction in erythropoietic cells

Megakaryocytes
-are conspicuous but are usually smaller in size than normal

Cytogenetic studies on blood and bone marrow cells
show the characteristic chromosomal abnormality called
the philadelphia (Ph) chromosome seen in 90-95 % cases
of CML.
- is identified by microsatellite PCR/ by FISH

75. NORMAL ADULT BONE MARROW
COUNTS
• Fat /cell ratio: 50:50
• Myeloid / Erythroid ratio: 2 to 4 : 1( mean 3:1)
• Myeloid series : 30-45%
• Erythroid series : 10-15%
• Myeloblasts : 0.1- 3.5%
• Promyelocytes: 0.5-5%
• Megakaryocytes : 0.5%
• Lymphocytes : 5-20%
• Reticulocytes : 0.1-2%

76. (3) Cytochemistry
- The only significant finding on cytochemical stains is
reduced scores of neutrophil alkaline phosphatase (NAP)
which helps to distinguish CML from myeloid leukaemoid
reaction
-Leukaemoid reaction is defined as a reactive excessive
leucocytosis in the peripheral blood resembling that of
leukemia in a patient who does not have leukaemia. Here
NAP is increased.

77. • (4) Other investigations
➔
➔
➔
➔
Elevated serum vitamin B12 and vitamin B12 binding
capacity- is due to ↑ in the transcobalamin present in
neutrophil granules
Elevated serum uric acid levels
Elevated serum LDH
Blood sugar may be falsely reduced due to glucose
uptake and metabolism by leucocytes

78. TREATMENT
• Pathophysiology of CML:
●
●
●
●
The t(9,22) involves fusion of BCR(breakpoint cluster
region) gene on chr 22q11 with ABL(abelson murine
leukaemia virus) gene located on chr 9q34.
The fusion product so formed is termed “Ph chromosome
t(9,22)(q34;11),BCR/ABL”
This brings about the following functional changes
-ABL protein is activated to function as a tyrosine kinase
that in turn activates the other kinases which inhibits
apoptosis

80. -Ability of ABL to act as DNA binding protein is altered
-Binding of ABL to actin of the cytoskeleton is increased
Exact mechanism of progression of CML to the blastic
phase is not known. But following mechanisms may be
responsible
-structural alterations in p53 and Rb gene
-alterations in RAS and MYC oncogenes

81. TREATMENT
• A) Treatment of chronic phase
• 1. Imatinib
MOA- competitively inhibits the ATP binding site of the
ABL kinase and thus promotes the apoptosis in BCR/ABL
+ve cells and thus eliminates them
It reduces the uncontrolled proliferation of white cells
Recommended as 1st line therapy in chronic phase

82. Produces complete cytogenetic response[
disappearance of Ph chromosome ] in 76% cases at 18
months of therapy
Patients are monitered by repeated bone marrow
examination until a complete cytogenetic response, and
then by 3 monthly microsatellite PCR/ by FISH
Side effects: fluid retention, nausea, muscle
cramps, diarrhoea, skin rash, myelosuppression
Resistance to imatinib results from over expression of BCRABL gene or genetic alteration

83. If a patient fails to respond to imatinib then
2nd generation tyrosine kinase inhibitors{ dasatinib and
nilotinib } can be used
or
Allogenic bone marrow transplantation
or
Classical cytotoxic drugs such as hydroxyurea(hydroxy
carbamide), melphalan, busulphan
or
Interferon

84. 2. ALLOGENIC B.M
TRANSPLANTATION
●
●
●
Indicated in patients <35 years who have a suitable
donor
Best results are obtained when the transplantation is done
in early chronic stable phase
It can result in permanent disappearance of philadelphia
chromosome +ve clone and hence can cure CML in
early stages

85. Procedure:
- healthy marrow or blood stem cells from a donor are
infused I.V. Into the recipient, who has been suitably
'conditioned'.
-The conditioning treatment (chemotherapy with or without
radiotherapy) destroys the malignant cells and
immunosuppresses the recipient, as well as ablating the
recipient's haematopoietic tissues
-The injected donor cells home to the marrow engraft and
produce enough erythrocytes, granulocytes and platelets
for the patient's needs after about 3-4 weeks

86. -During this period of aplasia patients are at risk of infection
and bleeding, and require intensive supportive care
-It may take several years to regain normal immunological
function
-ADVANTAGE: is that the donor's immunological system can
recognise the residual malignant recipient cells and
destroy them. This can be boosted post-transplantation by
the infusion of T cells taken from the donor, so called donor
lymphocyte infusion(DLI)

87. Complications :
-mucositis
-infection
-bleeding
-cataract formation
-pneumonitis
-infertility
-graft v/s host disease
-secondary malignant
disease

88. 3. CYTOTOXIC DRUGS
●
●
Hydroxy urea was previously used widely for initial control
of disease, and is still useful in this this context or in
palliative situations.
It does not diminish the frequency of the Ph chr or affect
the onset of blast cell transformation.

89. 4. INTERFERON Α
-It can induce remission and maintain control in chronic
stable phase.
- Not effective in accelerated or blast phase.
-Dose: 3-9 mega units/day i.m or s.c
-may be combined with cytosine arabinoside.
-It brings about:
↓ in bone marrow cellularity
↓ in no. of Ph +ve cells in 20% of cases
Elimination of Ph chromosome in 5% of cases
Reduction of platelet count when it is very high.

90. • - Adverse effects: flu like syndrome, wt
loss, fatigue, nausea, vomiting, headache.
• 5. Others:
➔
Splenic irradiation
➔
Splenectomy
➔
Leucopheresis
•

91. LEUKAPHERESIS AND
SPLENECTOMY
Leukapheresis :
-It may control the blood count in chronic phase CML
-But, expensive and cumbersome
-Useful in emergencies where leukostasis related complications like pulmonary
failure or CVA are likely.
-Also useful in pregnant women, in whom it is to avoid potentially teratogenic
drugs.

92. Splenectomy :
-It was used in the past because of the suggestion that evolution to the acute
phase might occur in spleen.
-However, this is not the case, and splenectomy is now reserved
a) For symptomatic relief of painful splenomegaly unresponsive to imatinib or
chemotherapy.
b) For significant anemia or thrombocytopenia associated with hypersplenism.
Splenic irradiation is used rarely to reduce the size of the spleen.

93. B) ACCELERATED PHASE
1. Imatinib
2. Hydroxycarbamide ( can be an effective single agent)
3. Low dose cytarabine

94. C) WHEN BLAST TRANSFORMATION
OCCURS
The type of blast cell should be determined
1. If disease is lymphoblastic, treatment is similar to acute
leukaemia and response to the treatment is better.
-Aim is to destroy the leukaemic clone of cells without
destroying the residual normal stem cell from which
repopulation of the haematopoietic tissues will occur.
-there are 3 phases

95. • Phase 1[Remission induction]→ The bulk of the tumour is
destroyed by combination chemotherapy. They require
intensive supportive care.
• Phase 2[Remission consolidation]→ This consists of a no. of
courses of chemotherapy which attacks the residual
disease.
• Phase 3[Remission maintenance]→ consisting of a
repeating cycles of drug administration. This may extend
for up to 3 years.

96. • Induction
→Daunorubicin, Methotrexate, vincristine, Prednisolone.
• Consolidation→Daunorubicin, Methotrexate, Cytarabine,
Etoposide.
• Maintenance→Methotrexate, Vincristine, Prednisolone, M
ercaptopurine.

97. INTENSIVE SUPPORTIVE CARE

Anemia : is treated with red cell concentrate transfusions.

Bleeding :
-Thrombocytopenic bleeding requires platelet
transfusions, unless the bleeding is trivial.
-Prophylactic platelet transfusion should be given to
maintain the platelet count above 10x10 9/L.
-coagulation abnormalities occur and need accurate
diagnosis and treatment as appropriate

98. 
Control of infections with appropriate antibiotics

Metabolic problems:
-cellular breakdown during chemotherapy releases
intracellular ions and nucleic acid breakdown products
causing
hyperkalaemia, hyperuricaemia, hyperphosphataemia, an
d hypocalcaemia
-this may cause renal failure
-Allopurinol and I.V. Hydration are given to try to prevent
this.

99. - Prophylactic rasburicase(a recombinant urate oxidase
enzyme) can be used.
-occasionally, dialysis may be required.

Psychological problems:
-Delusions, hallucinations are not uncommon.
-patient should be kept informed, and their questions
answered and fears allayed as far as possible
-An optimistic attitude from the staff is vital.

100. COMPLICATIONS

101. Fatigue : The diseased WBC’S crowd out healthy RBC’S and anemia occurs.
This leads to tiredness, easy fatiguability, generalized weakness, lethargy and
headache.
• Treatment of CML also can cause a drop in RBC’S
Excess bleeding:
• -is due to ↓ in platelet count.
• -epistaxis, bleeding from gums, petechiae
Pain : CML can lead to bone pain or joint pain as the bone marrow expands
when excess WBC build up.

102.  Enlarged spleen:
- some of the extra blood cells produced in CML are stored in
spleen.
- This causes splenomegaly and it takes up space in the
abdomen and makes the patient feel full even after small
meals.
- Or causes pain in the left upper part of the abdomen.
 Infections :
• -Although people with CML have too many WBC, these cells
are often diseased an don’t function properly.
• -In addition, treatment can cause further ↓ in WBC
 Thrombosis : is due to leukostasis which may lead to pulmonary
failure and CVA.