LEUKEMIA Flashcards
a malignant disease characterized by unregulated proliferation of one cell type.
LEUKEMIA
leukemia may involve any of the ____ or a ____ common to several cell lines
cell lines; stem cell
leukemias 2 major groups
chronic and acute leukemia
the onset is insidious, the disease is usually less aggressive, and the cells involved are usually more mature cells
chronic leukemia
the onset is usually rapid, the disease is very aggressive, and the cells involved are usually poorly differentiated with many blasts.
acute leukemia
Both acute and chronic leukemias are further classified according to the prominent cell line involved in the expansion:
If the prominent cell line is of the myeloid series it is a myelocytic leukemia (sometimes also called granulocytic)
If the prominent cell line is of the lymphoid series it is a lymphocytic leukemia
four basic types of leukemia
Acute myelocytic leukemia
Acute lymphocytic leukemia
Chronic myelocytic leukemia
Chronic lymphocytic leukemia
type of leukemia that includes myeloblastic, promyelocytic, monocytic, myelomonocytic, erythrocytic, and megakaryocytic
Acute myelocytic leukemia (AML)
type of leukemia that includes T cell, B cell, and Null cell
Acute lymphocytic leukemia (ALL)
type of leukemia that includes myelocytic and myelomonocytic)
Chronic myelocytic leukemia (CML)
a type of leukemia that includes plasmocytic {multiple myeloma}, Hairy cell, prolymphocytic, large granular cell lymphocytic, Sezary’s syndrome, and circulating lymphoma
Chronic lymphocytic leukemia (CLL)
predisposing factors of leukemia (etiology)
host factors
environmental factors
Some individuals have an _____ to develop leukemia
inherited increased predisposition
There is an increased incidence in those with an ______ or ________ of chromosomes (such as _____).
inherited tendency for chromosome fragility or abnormality ; those with increased numbers ; Down’s syndrome
Many of these diseases are characterized by _______.
chromosomal translocations
There is an increased incidence in those with ________.
hereditary immunodeficiencies
There is an increased incidence in those with chronic marrow dysfunction such as those with…
myeloproliferative diseases, myelodysplastic syndromes, aplastic anemia, or paroxsymal nocturnal hemoglobinuria.
Environmental factors
Exposure to ionizing radiation
Exposure to mutagenic chemicals and drugs
Viral infections
incidence of leukemia
Acute leukemias can occur in all age groups
Chronic leukemias are usually a disease of adults
ALL is more common in _____
children
AML is more common in _____
adults
CLL is extremely rare in ____ and unusual before the age of ___
children ; 40
CML has a peak age of ____
30-50
acute leukemias on the ff.
Age
Clinical onset
Course (untreated)
Leukemic cells
Anemia
Thrombocytopenia
WBC count
Lymphadenopathy
Splenomegaly
Age = all ages
Clinical onset = sudden
Course (untreated) = 6 mos. or less
Leukemic cells = immature >30% blasts
Anemia = prominent
Thrombocytopenia = prominent
WBC count = varibale
Lymphadenopathy = mild
Splenomegaly = mild
chronic leukemias on the ff.
Age
Clinical onset
Course (untreated)
Leukemic cells
Anemia
Thrombocytopenia
WBC count
Lymphadenopathy
Splenomegaly
Age = usually adults
Clinical onset = insidious
Course (untreated) = 2-6 years
Leukemic cells = more mature cells
Anemia = mild
Thrombocytopenia = mild
WBC count = increased
Lymphadenopathy = present;often prominent
Splenomegaly = present;often prominent
acute leukemia is a result of malignant transformation of a stem cell leading to _____
unregulated proliferation
acute leukemia is also a result of Arrest in maturation at the ______
primitive blast stage (Remember that a blast is the most immature cell that can be recognized as committed to a particular cell line)
clinical feature: Leukemic proliferation, accumulation, and invasion of normal tissues, including the ____________ cause lesions ranging from rashes to tumors.
liver, spleen, lymph nodes, central nervous system, and skin.
clinical feature: A humoral mediator from the leukemic cells may inhibit _______
proliferation of normal cells.
clinical feature: Failure of the bone marrow and normal hematopoiesis may result in ______
pancytopenia with death from hemorrhaging and infections.
lab diagnosis is based first on,
Finding a significant increase in the number of immature cells in the bone marrow including blasts, promyelocytes, promonocytes (>30% blasts is diagnostic)
lab diagnosis is based secondly on,
Identification of the cell lineage of the leukemic cells
peripheral blood
Anemia (normochromic, normocytic)
Decreased platlets
Variable WBC count
The degree of peripheral blood involvement determines classification
leukemic
subleukemic
aleukemic
increased WBCs due to blasts
leukemic
blasts without increased WBCs
subleukemic
decreased WBCs with no blasts
aleukemic
Classification of the immature cells involved may be done by
Morphology
Immunologic markers (immunophenotyping)
an experienced morphologist can look at the size of the blast, the amount of cytoplasm, the nuclear chromatin pattern, the presence of nucleoli and the presence of auer rods (are a pink staining, splinter shaped inclusion due to a rod shaped alignment of primary granules found only in myeloproliferative processes) to identify the blast type
Morphology
the myeloblast is a large blast with a moderate amount of cytoplasm, fine lacey chromatin, and prominent nucleoli. 10-40% of myeloblasts contain auer rods.
AML
in contrast to the myeloblast, the lymphoblast is a small blast with scant cytoplasm, dense chromatin, indistinct nucleoli, and no auer rods
ALL
help to classify the lineage of a leukemic cell (myeloid versus lymphoid)
Cytochemistry
found in the primary granules of granulocytic cells starting at the late blast stage. Monocytes may be weakly positive.
Myeloperoxidase
stains phospholipids, neutral fats and sterols found in primary and secondary granules of granulocytic cells and to a lesser extent in monocytic lysosomes. Rare positives occur in lymphoid cells
Sudan Black
used to identify monocytic cells which are diffusely positive. T lymphocytes may have focal staining
Nonspecific esterase
May be found in myeloblasts and lymphoblasts. T lymphocytes have a high level of ____ and this can be used to help make a diagnosis of acute T-lymphocytic leukemia.
acid phosphatase
located in the secondary granules of segmented neutrophils, bands and metamyelocytes.
Leukocyte alkaline phosphatase
Leukocyte alkaline phosphatase score
The LAP score is determined by counting 100 mature neutrophils and bands. Each cell is graded from 0 to 5. The total LAP score is calculated by adding up the scores for each cell.
these are used mainly for lymphocytes, i.e., for determining B cell or T cell lineage. These tests rely on antibodies made against specific surface markers.
Immunologic markers (immunophenotyping)
Immunologic markers (immunophenotyping) constitute what we would call the ______ and in an indirect assay they are allowed to react with the cells and ______ is then washed away.
primary antibody ; unbound antibody
______ (secondary antibody) against the primary antibody is added and allowed to react and then _____ is washed away.
Fluorescently labeled antibody ; unbound secondary antibody
The cells are then sent through a ______ that will determine the _____ of cells that have a fluorescent tag and which are thus positive for the presence of the surface marker to which the primary antibody was made.
flow cytometer ; number.
In a direct assay, the primary antibody is _______
fluorescently labeled.
This is a unique DNA polymerase present in stem cells and in precursor B and T lymphoid cells.
TERMINAL DEOYXTIDYL TRANSFERASE
TERMINAL DEOYXTIDYL TRANSFERASE high levels are found in 90% of _____
lymphoblastic leukemias.
TERMINAL DEOYXTIDYL TRANSFERASE can also be detected using ______ and ______.
appropriate antibodies and flow cytometry
a study that can now be used for diagnosis and for prognosis of hematologic malignancies.
cytogenetics
Many leukemias (and lymphomas) are characterized by specific chromosomal abnormalities, including specific translocations and aneuploidy. The specific type of malignancy can be identified based on the specific abnormality or translocation. These may be identified by
Looking at the karyotypes of the chromsomes from the abnormal cells
DNA based tests – these tests are very useful for following the course of the disease
RT-PCR
Southern blotting
A ______ is usually associated with a better prognosis.
normal karyotype
Acute lymphoblastic leukemia may be classified on the basis of the cytological features of the lymphoblasts into;
L1
L2
L3
This is the most common form found in children and it has the best prognosis.
L1
in L1, The cell size is ______ with ______ nuclear chromatin and ____ nucleoli.
small ; fine or clumped homogenous nuclear chromatin ; absent or indistinct nucleoli
in L1, The nuclear shape is ____, occasionally _____ or _____.
regular ; clefting or indented
in L1, The cytoplasm is _____, with slight to moderate _____ and variable _____.
scant ; basophilia ; vacuoles
This is the most frequent ALL found in adults.
L2
in L2, The cell size is ______ and _______ with _____ nuclear chromatin and _____ nucleoli.
large and heterogenous ; variable ; prominent
in L2, the nucleus is ______, _______ and _____
irregular, clefting and indented.
in L2, the cytoplasm is ______ and often ______ with variable ______ and variable ______.
variable ; moderate to abundant ; basophilia ; vacuoles.
This is the rarest form of ALL.
L3
in L3, the cell size is ____, with ____ homogenous nuclear chromatin containing _____ nucleoli.
large ; fine ; prominent
in L3, the nucleus is regular ______.
oval to round
in L3, the cytoplasm is moderately _____ and is deeply _______
abundant ; basophilic and vacuolated.
ALL may also be classified on the basis of immunologic markers into:
Early pre-B ALL
Pre-B ALL
B ALL
T ALL
Null or unclassified ALL (U ALL) - lack B or T markers and may be the committed lymphoid stem cell)
ALL is primarily a disease of young children (2-5 years), but it can also occur in adults
acute leukemia incidence
pancytopenia with resulting fatigue, pallor, fever, weight loss, irritability, anorexia, infection, bleeding, and bone pain.
acute leukemia clinical findings
L1 occurs in _______, L2 in _____, and L3 is called _____
children ; adults ; Burkitts leukemia
age, WBC count, and cell type are the most important prognostic indicators
acute leukemias prognosis
Patients younger than ___ and greater than ___ have a poor prognosis
1 ; 13
If the WBC count is _____ at presentation, the prognosis is good
< 10 x 10^9/L
If the WBC count is ______ at presentation the prognosis is poor
> 20 x 10^9/L
____ ALL (more common in males) has a poorer prognosis than any of the ____ ALLs which have a cure rate of _____
T cell ; B cell ; 70%
Acute leukemias with mixed lineage – occasionally there are acute leukemias that are biphenotypic and display phenotypes for two different lineages
B lymphoid/myeloid
T lymphoid/myeloid
B/T lymphoid
Myeloid/Natural killer
A rare trilineage leukemia has also been seen (was B/T lymphoid/myeloid!)
classification of Acute myeloid leukemia depends upon
Bone marrow blast morphology
Degree of cell maturation
Cytochemical stains
Immunophenotyping
also called acute granulocytic leukemia
Acute myeloid leukemia
AML is divided into 7 different classifications
M1
M2
M3 (M3m)
M4
M5 (M5A, M5B)
M6
M7
myeloblastic without maturation
M1
in M1, the bone marrow shows ___ blasts and ___ promyelocytes
≥ 90% ; <10%
the disease occurs in older adults
M1
myeloblastic with maturation
M2
in M2, The bone marrow shows ____ blasts and ____ promyelocytes
30-89% ; > 10%
characterized by an 8,21 chromosomal translocation and occurs in older adults
M2
hypergranular promyelocytic
M3
This form of AML has a bone marrow with ___ blasts
> 30%
Is more virulent than other forms
Occurs with a medium age of 39
The WBC count is decreased
It is characterized by a 15,17 chromosomal translocation
M3
in M3, Treatment causes a release of the ____ and may send the patient into _____ and _____
granules ; disseminated intravascular coagulation ; subsequent bleeding
hypogranular promyelocytic
The WBC count is increased.
It is characterized by a 15,17 translocation
M3M
IN M3M, The bone marrow has_____ blasts
> 30%
Like the M3 type, M3M _____
treatment causes a release of the granules and may send the patient into disseminated intravascular coagulation and subsequent bleeding
acute myelomonoblastic leukemia
M4
in m4, Both ______ are seen in the bone marrow and peripheral blood
myeloblasts and monoblasts
in m4, Infiltration of extramedullary sites is more common than with the _____
pure granulocytic variants
acute monoblastic leukemia
M5
in M5, _____ of the nonerythroid cells in the bone marrow are _____
> 80% ; monocytic
There is extensive infiltration of the gums, CNS, lymph nodes and extramedullary sites, This form is further divided into:
M5A
M5B
Poorly differentiated (>80% monoblasts)
M5A
Well differentiated (<80% monoblasts)
M5B
This is rare and is characterized by a bone marrow having a predominance of erythroblasts
M6 – erythroleukemia
3 sequentially morphologically defined phases of M6
Preponderance of abnormal erythroblasts
Erythroleukemia – there is an increase in both erythroblasts and myeloblasts
Myeloblastic leukemia – M1, M2, or M4
in M6, anemia is common (Yes or No)
Yes
This is a rare disorder characterized by extensive proliferation of megakaryoblasts, atypical megakaryocytes and thrombocytopenia
M7 - Acute megkaryoblastic leukemia
2 goals of leukemia treatment
Eradicate the leukemic cell mass
Give supportive care
Except for ALL in children, cures are not common but ______ is.
complete remission (absence of any leukemia related signs and symptoms and return of bone marrow and peripheral blood values to within normal values)
There are four general types of therapy
Chemotherapy
Bone Marrow Transplant
Radiotherapy
Immunotherapy
Monoclonal antibodies
usually a combination of drugs is used
chemotherapy
stimulate the patients own immune system to mount a response against the malignant cells
immunotherapy
examples include Rituxin
monoclonal antibodies
WHO CLASSIFICATION includes different biologically distinct groups based on:
clinical features
cytogenetic and molecular abnormalities
morphology
a major difference between WHO and FAB classification is the blasts cut-off for a diagnosis of AML:
20% - WHO
30 % - FAB
AML with blasts 20 – 30 % by WHO can benefit from therapies for ________ that were approved by USFDA
MYELODYSPASIA
are neoplastic proliferative diseases that are characterized by an overproduction of immature and mature cells of various leucocyte types in the Bone Marrow and/or peripheral blood
leukemia
characterize by
a. symptoms of short duration
b. many immature cell forms in the Bone marrow and/or peripheral blood
c. elevated leucocyte count
acute leukemia
characterize by
a. symptoms of long duration
b. mostly mature cell forms in the Bone marrow and/or peripheral blood
c. total leucocyte counts that range from extremely elevated to less than normal
chronic leukemia
