Hema II Chapter 5 haematologic malignancy.ppt

Hematology

1. CHAPTER 5
HAEMATOLOGIC MALIGNANCY
1

2. 2

3. Introduction
Haematological malignancies are clonal diseases derived
from a single cell in the bone marrow or peripheral
lymphoid tissue which has undergone a genetic
alteration.
A combination of genetic and environmental factors
determine the risk of developing malignancy
Inherited factors – genetic diseases increase the
incidence of leukemia
Down’s syndrome, Bloom’s syndrome, Fanconi’s
anemia, ataxia telangiectasia
Environmental influences
Chemicals, drugs, radiation, infection
3

4. The genetics of malignant transformation
oMalignant transformation - accumulation of genetic
mutations in cellular genes
oThe genes involved in the development of cancer are divided
broadly into two groups:
Oncogene (dominant, gain of function)
 gene responsible for causing cancer.
Converted from proto-oncogene via mutations
(translocation, duplication and point-leading to over acting,
up-regulated)
 proto-oncogenes are normal genes codes for proteins that
are capable of controlling cell division and growth.
Tumour suppressor genes (recessive, loss of function)
Loss of gene function by deletion or inactivating point
mutation leading to malignant transformation
 in normal circumstances, tumour suppressor genes code
for proteins that block overt cell division and growth
4

5. Leukemia
- is a type of white blood cell cancer that affects the
blood and bone marrow. The disease develops when
blood cells produced in the bone marrow grow out
of control.
Causes
• High level radiation / toxin exposure
• Viruses
• Genes
• Chemicals
• Mostly unknown, “idiopathic”
5

6. Leukemia cont’d...
The leukemia are a group of disorders characterized by the
accumulation of abnormal white cells in the BM.
These abnormal cells may cause:
Bone marrow failure
A raised circulating white cell count
Infiltration of organs
Common but not essential features include:
Abnormal white cells in the peripheral blood
A raised total white cell count
Evidence of bone marrow failure (i.e., anemia,
neutropenia, thrombocytopenia) in the acute leukemia
Involvement of other organs (e.g., liver, spleen, lymph
nodes, meninges, brain, skin or testes)
6

7. Leukemia cont’d...
Although viruses cause several forms of leukemia in animals,
their role in humans is uncertain.
Only two viral associations are identified
Epstein-Barr virus, a DNA virus, associated with Burkitt's
lymphoma
Human T-cell lymphotropic virus type I, an RNA retrovirus,
associated with some T-cell leukemia and lymphoma
Exposure to ionizing radiation and certain chemicals (e.g.,
benzene, some anti-neoplastic drugs) is associated with an
increased risk of leukemia
 Some genetic defects (e.g., Down syndrome, Fanconi's anemia)
also predispose to leukemia
7

8. Classification of leukemia
oBased on natural history of the diseases (how quickly
the disease develops and gets worse)
– Acute: fatal within weeks or months of diagnosis
– Chronic: fatal in years in the absence of treatment
o On the basis of morphology and Cytochemistry, acute
leukemia is further subdivided into:
Acute myeloid (myeloblastic/myelogenous) leukemia
(AML)
Acute lymphoblastic (lymphocytic) leukemia (ALL)
8

9. Classification of Leukemia cont’d...
AML is further subdivided into eight variants on a
morphological basis according to the French-American-
British (FAB) scheme (M
0
– M
7
)
ALL is subdivided on a morphological basis according to the
French-American-British (FAB) classification into L
1, L
2, and L
3
The chronic leukemia comprise two main types:
Chronic myeloid leukemia (CML)
Chronic lymphocytic (lymphatic) leukemia (CLL)
Other chronic types include:
Hairy cell leukemia, HCL
Prolymphocytic leukemia, PLL
Various leukemia/lymphoma syndromes
9

10. Epidemiology
•AML - occurs in both in adults (80%) and children.
•ALL - the most common type seen in children (80%), but
also seen in adults, most often over 65.
•CML - occurs mostly in adults, young and old.
•CLL - most often seen in people over age 55, can affect
younger adults, but almost never seen in children.
10

11. Treatment
• Chemotherapy
• Immunotherapy
• Radiation
• Bone marrow transplant
Diagnostic methods:
- Morphological
- Cytochemistry
- Immunophenotyping
- Cytogenetic / Molecular
11

12. The Acute Leukemia
The leukemic cell population in ALL and AML probably
result from clonal proliferation by successive divisions
from a single abnormal stem or progenitor cell
There are over 50% myeloblasts or lymphoblasts in the
bone marrow at clinical presentation, and these blast
cells fail to differentiate normally but are capable of
further divisions.
Replacement of the normal hemopoietic precursor cells
of the bone marrow by myeloblasts or lymphoblasts
and, ultimately results in bone marrow failure
12

13. The Acute Leukemia cont’d...
The clinical condition of the patient can be correlated
with the total number of leukemic cells in the body.
When the abnormal cell number approaches 10
12
, the
patient is usually gravely ill with severe bone marrow
failure.
Peripheral blood involvement by the leukemic cells and
infiltration of organs such as the spleen, liver and lymph
nodes (RES) may not occur until the leukemic cell
population comprised 60% or more of the marrow cell
total.
13

14. The Acute Leukemia cont’d...
The clinical presentation and mortality in acute leukemia
arises mainly from:
Neutropenia
Thrombocytopenia, and
Anemia because of bone marrow failure
Organ infiltration, e.g., of the meninges or testes
(less commonly)
14

15. The Acute Leukemia cont’d...
The acute leukemia comprise over half of the leukemia
seen in clinical practice
ALL is the common form in children
Its incidence is highest at 3-4 years
Falls off by 10 years
There is a lower frequency of ALL after 10 years of
age with a secondary rise after the age of 40
AML occurs in all age groups
It is the common form of acute leukemia in adults
including the elders
15

16. Laboratory features in Acute Leukemia
AML -Blood(Lab) features
• Anemia
- Normocytic Normochromic (NCNC)
• Red cell morphology: mildly abnormal ( anisocytosis,
poikilocytosis)
-NRBCs
•Thrombocytopenia- over half patients, platelet count <
50,000/mm3
- giant platelets
- poorly granulated platelets
• In elevated leukocytosis – low proportion of mature
Neutrophils (neutropenia)
16

17. • Myeloblast
- almost always present
- may range from very rare to 95% of leukocytes
• Auer rods: present in a very small percentage of blast
cells (M2, M3, M4)
17
Laboratory features of Acute Leukemia cont’d…

18. Laboratory features of Acute Leukemia cont’d…
In AML M
6 (erythroleukemia) many erythroblasts may be
found
The bone marrow is hypercellular with a marked
proliferation of leukemic blast cells which amount to over
50% - 75% of the marrow cell total.
In ALL, the marrow may be difficult to aspirate because of
increased reticulin fiber.
In AML M
7, the patient typically has an acute onset of
Pancytopenia with BM fibrosis.
18

19. 19
Figure 5.7 Type III blasts may have
numerous azurophilic granules

20. 20

21. Differentiate AML/ALL
Myeloblasts are distinguished from Lymphoblasts in that:
 Myeloblasts are usually larger than lymphoblasts
Myeloblasts cytoplasm is more abundant
Fine azurophilic granules (particularly in promyelocytic
leukemia)
delicate nuclear chromatin
1-4 nucleoli
Myeloblasts Lymphoblasts

22. Differentiation of ALL from AML ...
In most cases, the clinical features and morphology on
routine staining separate ALL from AML
In ALL, the blasts show no differentiation (with the
exception of B-ALL)
In AML, some evidence of differentiation to granulocytes
or monocytes is seen in the blasts or their progeny
Special test (e.g., Cytochemistry, gene rearrangement studies
and chromosome analysis) are needed when the cells are
undifferentiated to:
Confirm the diagnosis of AML or ALL, and
Subdivide cases of AML or ALL into their different subtypes
22

23. •Auer rods ¼ of cases (diagnostic of AML), but Auer rods are
not always present in myeloblasts while auer rods are totally
absent in ALL
• Leukemic myeloblasts react to histochemical staining for
MPO/SB, on the other hand Lymphoblasts are MPO/SB/ NSE
= Negative, and PAS = Positive , Fig [a, b]
• But to identify M0 (which is Negative for MPO, SB ) from ALL,
Immunophenotyping for Myeloid Ag is necessary [c]
MPO+ SB + CD 13 +[b][a] [c]
23

24. AML – Classification
1) WHO Classification
- WHO classification (2001) requires only 20% of
blasts in bone marrow or blood to diagnose
AML (was 30% under FAB), which eliminates
Myelodysplastic category of “refractory anemia
with excess blasts in transformation”
24

25. 2) AML French-American-British (FAB) classification
system divided AML into M0-M7
Table : Simplified summary of the FAB classification
of acute myeloid leukaemia
25

26. 26

27. ACUTE LYMPHOBLASTIC LEUKEMIA
• ALL is a disease resulting from mutation in a lymphoid
stem cell of either B or T lineage.
- The cell carrying the mutation gives rise to an expanding clone
- The peak incidence is in early childhood, particularly between the
ages of 2 and 10 years
•ALL can be further classified on the basis of cytology,
immunophenotype or cytogenetic and molecular genetic
features
ALL - WHO classification
- WHO classification system includes former FAB classifications
ALL-L1 and L2
- FAB L3 is now considered Burkitt’s lymphoma
27

28. •A morphological classification in to L1, L2 and L3 categories
has been proposed by the FAB group.
Morphological features of ALL subtypes
28

29. L
1 ALL =
L2 ALL
L3 ALL
= large varied cells with
 
vacuoles
 
(bubble-like features)
small uniform cells
= large varied cells
29

30. MO: AML MINIMALLY DIFFERENTIATED
30

31. M1: AML WITHOUT MATURATION
31

32. M2: AML WITH MATURATION
AUER
ROD
32

33. M3: HYPERGRANULAR (ACUTE)
PROMYELOCYTIC
33

34. M4: ACUTE MYELOMONOCYTIC
34

35. M5a: ACUTE MONOCYTIC – POORLY
DIFFERENTIATED
35

36. M5b: ACUTE MONOCYTIC –
DIFFERENTIATED
36

37. M6: ERYTHROLEUKEMIA
37

38. M6: ERYTHROLEUKEMIA
38

39. M7: ACUTE MEGAKARYOBLASTIC
39

40. Acute Plasmacytic Leukemia
40

41. Lymphoblasts vs Myeloblasts
CharacteristicsALL
(Acute
Lymphoblastic
Leukemia)
AML
(Acute Myeloid Leukemia)
Blast Size Small Large
Cytoplasm Scanty Moderate
Chromatin Dense Fine, Lacy
Nucleoli Indistinct Prominent
Auer Rods Absent Present in
approximately 50%
41

42. Which one is the myeloblast?
42

43. ANSWER: Which is the
Myeloblast?
MYELOBLAST:
Large Size, Moderate Cytoplasm,
Fine Chromatin, Prominent Nucleoli,
& Auer rods
43

44. The Chronic Leukemia
Chronic Myeloid Leukemia (CML)
>20% of all the leukemia
seen most frequently in middle age
Due to replacement of normal bone marrow by cells
with an abnormal chromosome- Philadelphia or Ph
chromosome
Affects all cell lines
70% of patients develop acute leukemia
Assignment: what is Philadelphia chromosome?
44

45. Chronic Myeloid Leukemia (CML) cont’d
Formation of the Philadelphia chromosome resulting in a
BCR-ABL fusion gene that generates a fusion protein
(p210) responsible for the CML phenotype
45

46. Chronic Myeloid Leukemia (CML) cont’d…
Laboratory findings in CML
Leukocytosis >50x10
9
/l and sometimes >500x10
9
/L
Spectrum of myeloid cells
Neutrophils and myelocytes increased
Ph chromosome
Hypercellular bone marrow with granulopoietic
predominance
low Neutrophil alkaline phosphatase (NAP) score
46

47. Laboratory findings in CML cont’d
Increased circulating basophils
Normochromic normocytic anemia
Platelet count may be increased (most frequently),
normal or decreased
Serum vitamin B
12 and vitamin B
12-binding capacity
are increased
Serum uric acid is usually raised
47

48. Chronic lymphocytic leukemia, CLL
Accounts for 25% or more of the leukemia
Accumulation of large numbers of lymphocytes to 50 -100 times
the normal lymphoid mass
Occurs in older subjects and is rare before 40 years
The male to female ratio is 2:1
Result:
•Bone marrow failure
•Monoclonal population of B lymphocytes
•Lymphadenopathy
•Immunological failure results from reduced humoral and
cellular immune processes with a tendency to infection
48

49. Chronic lymphocytic leukemia cont’d
Laboratory findings in CLL
Lymphocytosis
The absolute lymphocyte count is >5x10
9
/L and
may be up to 300x10
9
/L or more
Between 70% and 99% of white cells in the blood
film appear as small lymphocytes
Smudge or smear cells are also present
Normocytic normochromic anemia is present in later
states due to marrow infiltration or hypersplenism
49

50. Laboratory findings in CLL …
Thrombocytopenia occurs in many patients
Bone marrow aspiration shows lymphocytic
replacement of normal marrow elements
Lymphocytes comprise 25-95% of all the cells
Reduced concentrations of serum
immunoglobulins
More marked with advanced disease
50

51. CHRONIC LYMPHOCYTIC LEUKEMIA
SMUDGE
CELLS
51

52. Hairy Cell Leukemia
•Also known as leukemic reticuloendotheliosis
•It is a slow growing leukemia
•It is most common in older white males
•It is an unusual disease of peak age 40-60 years
•Men are affected nearly four times as frequently as
women
•It is a type of CLL.
•The disease is characterized clinically by features of
Pancytopenia
•The spleen may be moderately enlarged, splenomegally.
52

53. Hairy Cell Leukemia cont’d
There is a monoclonal proliferation of cells with an irregular
cytoplasmic outline (‘hairy’ cells, a type of B lymphocyte) in:
The peripheral blood
Bone marrow
Liver and other organs
The number of hairy cells in the peripheral blood is variable
The bone marrow trephine shows a characteristic
appearance of mild fibrosis and a diffuse cellular infiltrate
The patients may have arthritis, serositis or vasculitis
53

54. CML CLL
CLL
54

55. CMML (Chronic
Myelomonocytic Leukemia)
Hairy Cell Leukemia
Prolymphocytic
Leukemia (PLL)
55

56. Myelodysplastic Syndromes (MDS)/Myelodysplasia
A heterogeneous group of disease states that usually present
as peripheral blood cytopenia with a hypercellular bone
marrow
Most common in the elderly and males are more commonly
affected
There is a tendency to progress to AML
The fundamental disorder is the clonal proliferation of stem
cells that produce progeny that fail to mature normally
The maturation defect is more subtle; mature forms
develop but they are often morphologically atypical
(“dysplastic”) and frequently dysfunctional as well
56

57. Myelodysplastic Syndromes (Myelodysplasia) cont’d
The MDS are classified into five subgroups:
Refractory anemia (RA)
RA with ring sideroblasts (RARS)
RA with excess blasts (RAEB)
RAEB in transformation (RAEB-t)
Chronic Myelomonocytic leukemia (CMML)
57

58. Myelodysplastic Syndromes (Myelodysplasia) cont’d
Laboratory features of MDS
Peripheral blood
Pancytopenia is a frequent finding
The red cells are usually macrocytic or dimorphic but
occasionally hypochromic; Normoblasts may be present
The reticulocyte count is low
Granulocytes are often reduced
Show lack of granulation, “hypogranulation”
Their chemotactic, phagocytic and adhesive functions
are impaired
58

59. Laboratory features cont’d…
The Pelger abnormality (single or bilobed nucleus in
neutrophils) is often present
In CMML, monocytes are >1.0x10
9
/L in the blood
The total white blood count may be >100x10
9
/L
The platelets may be unduly large or small and are
usually decreased in number but in 10% of cases are
elevated
Variable numbers of myeloblasts in blood indicating
poor prognosis
59

60. Laboratory features cont’d…
Bone marrow
The Cellularity is usually increased
Ring sideroblasts may occur in all five FAB types
Multinucleate normoblasts and other dyserythropoietic
features are seen
The granulocyte precursors
Show defective primary and secondary granulation, and
Cells which are difficult to identify as either agranular
myelocytes, monocytes or promonocytes are frequent
Megakaryocytes are abnormal with micro-, small binuclear
or polynuclear forms
Bone marrow biopsy shows fibrosis in 10% of cases
60

61. Malignant Lymphomas
This group of diseases is divided into:
Hodgkin’s disease, and
Non-Hodgkin’s lymphomas
In both, there is replacement of normal lymphoid
structure by collections of abnormal cells
Hodgkin’s disease is characterized by the presence of
Reed-Sternberg (RS) cells and
The non-Hodgkin’s lymphomas are characterized by
diffuse or nodular collections of abnormal
lymphocytes or, rarely, histiocytes
61

62. Hodgkin’s disease
It is a type of lymphoma characterized by the presence
of Reed-Sternberg cells
In many patients, the disease is localized initially to
single peripheral lymph node region and its subsequent
progression is by contiguity within the lymphatic system
RS cells and the associated abnormal and smaller
mononuclear cells are neoplastic and the associated
inflammatory cells represent a hypersensitivity response
by the host
After a variable period of containment within the lymph
nodes, the natural progression of the disease is to
disseminate to involve non-lymphatic tissue
62

63. Hodgkin’s disease cont’d
The disease can present at any age but is rare in
children
It has bimodal age incidence
First peak in young adults (age 20-30 years)
A second after the age of 50
There is an almost 2:1 male predominance
63

64. Laboratory findings in Hodgkin’s disease
Normochromic normocytic anemia is most common
One-third of patients have a Leukocytosis due to a
Neutrophil increase
Eosinophilia is frequent
Advanced disease is associated with lymphopenia
The platelet count is normal or increased during
early disease, and reduced in later stages
The ESR is usually raised and is useful in monitoring
disease progress
64

65. Laboratory findings in Hodgkin’s disease cont’d
Bone marrow involvement is unusual in early disease
It may be demonstrated by trephine biopsy,
usually in patients with disease at many sites
There is progressive loss of immunologically
competent T lymphocytes with reduced cell-
mediated immune reactions
Infections are common, particularly:
Herpes zoster
Cytomegalovirus
Fungal, e.g., Cryptococcus and Candida
Tuberculosis may occur
65

66. Laboratory findings in Hodgkin’s disease cont’d
Patients with bone disease may show:
Hypercalcaemia
Hypophosphataemia
Increased levels of serum alkaline phosphatase
 Serum lactate dehydrogenase (LDH) is raised initially in
30-40% of cases an indicates a poor prognosis
Elevated levels of serum transaminases may indicate
liver involvement
Serum bilirubin may be raised due to biliary obstruction
caused by large lymph nodes at the portal hepatitis
Hyperuricaemia may occur
66

67. HODGKIN’S LYMPHOMA
Reed-
Sternberg
Cell
67

68. Non-Hodgkin’s lymphomas
The clinical presentation and natural history of these malignant
lymphomas are more variable than in Hodgkin’s disease
Pattern of spread is not regular
A greater proportion of patients present with extra nodal
disease or leukemic manifestations
Laboratory findings in Non-Hodgkin’s lymphoma
A normochromic normocytic anemia is usual but auto-immune
hemolytic anemia may also occur
In advance disease with marrow involvement, there may be
neutropenia, thrombocytopenia (especially if the spleen is
enlarged) or leuco-erythroblastic features
Assignment: NHL
68

69. Laboratory findings in non-Hodgkin’s lymphomas cont’d
Lymphoma cells (‘cleaved follicular lymphoma’ or ‘blast’
cells) with variable nuclear abnormalities may be found in
the peripheral blood in some patients
Trephine biopsy of marrow shows focal involvement, usually
paratrabecular, in 20% of cases
Elevation of serum uric acid may occur
Abnormal liver function tests suggest disseminate disease
The serum LDH level is raised in more rapidly proliferating
and extensive disease and may be used as a prognostic
marker
69

70. Multiple Myeloma
It is a neoplastic monoclonal proliferation of bone
marrow plasma cells characterized by:
Lytic bone lesions
Plasma cell accumulation in the bone marrow, and
The presence of monoclonal protein in the serum
and urine
98% of cases occur over the age of 40 with a peak
incidence in the 7
th
decade.
70

71. Laboratory finding in multiple myeloma
In 98% of patients monoclonal protein occurs in the serum or
urine or both
The serum paraprotein is IgG in two-thirds
IgA in one-third
Rare IgM or IgD or mixed cases
Normal serum immunoglobulins (IgG, IgA and IgM) are
depressed
The urine contains Bence-Jones protein in two-thirds of cases
The bone marrow shows increased plasma cells often with
abnormal forms – ‘myeloma cells’
Immunological testing shows these cells to be monoclonal
B cells
Express the same immunoglobulin heavy and light chains
as the serum monoclonal protein
71

72. Laboratory finding in multiple myeloma cont’d
There is usually a normochromic, normocytic or
macrocytic anemia
Rouleaux formation is marked in most cases
Neutropenia and thrombocytopenia occur in advanced
disease
Abnormal plasma cells appear in the blood film in 15% of
patients
Leuco-erythroblastic changes are occasionally seen
High ESR
Serum calcium elevation occurs in 45% of patients
72

73. Laboratory finding in multiple myeloma cont’d
The blood urea is raised above 14mmol/l and serum
creatinine raised in 20% of cases
Proteinaceous deposits from heavy Bence-Jones
proteinuria, hypercalcaemia, uric acid, amyloid and
pyelonephritis may all contribute to renal failure
A low serum albumin occurs with advance disease
Serum β
2
-microglobulin (the light chain of the HLA class 1
antigens) is a useful indicator of prognosis
It partly reflects renal function
Levels less than 4mg/l imply a relatively good prognosis
73

74. MULTIPLE MYELOMA
74

75. Myeloproliferative Disorders
A group of conditions characterized by clonal
proliferation of one or more hematopoietic
components in the bone marrow and, in many
cases, the liver and spleen.
Polycythemia vera (PV)
Essential thrombocythemia
Myelofibrosis
75

76. Polycythemia vera (PV)
•Also referred to as erythrocytosis
•Refers to a pattern of blood cell changes that includes:
•An increase in hemoglobin above 17.5g/dl in adult males
and 15.5g/dl in females
•An accompanying rise in red cell count (above 6.0 x 10
12
/l
in males and 5.5x10
12
/l in females)
•Hematocrit (above 55% in males and 47% in females)
•The increase in red cell volume is caused by endogenous
myeloproliferation
•The stem cell origin of the defect is shown in many patients
by an over-production of granulocytes and platelets as well as
of red cells.
•This is a disease of older subjects with an equal sex incidence
76

77. Laboratory findings in PV
The hemoglobin, hematocrit and red cell count are
increased
A neutrophilia is seen in over half the patients, and some
have increased circulating basophils
A raised platelet count is present in about half the
patients
The neutrophil alkaline phosphatase (NAP) score is
usually increased
Increased serum vitamin B
12 and vitamin B
12-binding
capacity due to an increase in transcobalamin I
77

78. Laboratory findings in PV cont’d
The bone marrow is hypercellular with prominent
megakaryocytes.
Best assessed by a trephine biopsy
Clonal cytogenetic abnormalities may occur, but
there is no single characteristic change
Blood viscosity is increased
Plasma urate is often increased
Circulating erythroid progenitors are increased and
grow in vitro independently of added
erythropoietin
78

79. Essential thrombocythemia
Megakaryocyte proliferation and overproduction of platelets
is the dominant feature of this condition
There is sustained increase in platelet count above normal
(400x10
9
/l)
Recurrent hemorrhage and thrombosis are the principal
clinical features
Splenic enlargement (splenomegally) is frequent in the early
phase but splenic atrophy due to platelets blocking the
splenic mirocirculation is seen in some patients
There may be anemia due to:
Iron deficiency from chronic gastrointestinal or uterine
hemorrhage
The marrow disorder itself
79

80. Laboratory findings in Essential thrombocythemia
Abnormal large platelets and megakaryocyte
fragments may be seen in the blood film
The bone marrow is similar to that in PV
Platelet function tests are consistently abnormal
80

81. Myelofibrosis
There is the gradual replacement of the bone marrow by
connective tissue
A prime feature is extramedullary hematopoieis
Patients will typically have an enlarged spleen and liver
(hepatosplenomegally)
Typically affects patients more than 50 years old
Laboratory findings in Myelofibrosis
Anemia is usual but a normal or increased hemoglobin level
may be found in some patients
The white cell and platelet counts are frequently high at the
time of presentation
Later in the disease leucopenia and thrombocytopenia are
common
81

82. Laboratory findings in Myelofibrosis cont’d
A leuco-erythroblastic blood film is found
The red cells show characteristic ‘tear-drop’ poikilocytes
Bone marrow is usually unobtainable by aspiration
Trephine biopsy may show a hypercellular marrow
with an increase in reticulin-fibre pattern
Low serum and red cell folate, raised serum vitamin B
12
and vitamin B
12-binding capacity, and an increased
neutrophil alkaline phosphatase score are usual
High serum urate, LDH and hydroxybutyrate
dehydrogenase levels reflect the increased but largely
ineffective turnover of hematopoietic cells
Transformation to AML occurs in 10-20% of patients
82

83. Review Questions
1. Briefly describe the classification of leukemia
2.Explain the laboratory diagnosis of different form of
leukemia
3.Define Myelodysplastic syndrome and indicate the
hematological findings
4. What are the features of malignant lymphoma?
5. What are the characteristics multiple myeloma?
6.Describe myeloproliferative disorders
83