General introduction
Definition
Classification
Etiology
Incidence and prevalence
Definition
A heterogeneous group of neoplasms arising
from the malignant transformation of
hematopoietic cells.
Leukemia cells proliferate primarily in the bone
marrow and lymphoid tissues where they
interfere with normal hematopoiesis and immunity
They emigrate into the peripheral blood and
infilitrate other tissues
Etiology
The cause is not known in most patients
1. Virus : a unique human retrovirus
1) Human T-cell leukemiavirus I
(HTLV-I ): adult T-cell leukemia
(ATL)
2) Human T-cell leukemiavirus II
(HTLV-II) : chronic T-cell leukemia( CTL)
Etiology
2. Environmental factors
1) Ionizing radiation: causes leukemia in
experimental animal
2) Chemicals: benzene and other
aromatic hydrocarbons associated with
AML; treatment with alkylating agents and
other chemotherapeutic drugs lead to an
increased incidence of AML
Etiology
3. Genetic factors
Down syndrome
Classification
Acute
Acute myelogenous leukemia
Acute lymphocytic leukemia
( have a rapid clinical course)
Chronic
Chronic myelogenous leukemia
Chronic lymphocytic leukemia
(have a more prolonged nature course)
Incidence and prevalence
Incidence: 2.76 / 100,000 people / year in China
Morphology
Cytogenetic features
Morphology
Aneuploidy
Pseudodiploidy
Trisomy 8, 21; monosomy 7, 21
t(15,17)q(22,21),the PML-RARa fusion
gene for M3
Loss of an X or Y chromosome
Therapy
Temporary
Supportive care
Chemotherapy
Temporary care
Hyerleukocytosis
usually WBC > 200 ×109/L
headache confusion and dyspnea
Emergent leukapheresis
Supportive care
Antibiotictherapy
The use of Growth factors that stimulate
granulopoiesis
Component transfusion therapy
Antibiotic therapy
Pancytopenia after treatment is a sign of
effective drug action
The patient usually becomes febrile(>38oC),often
severe, and cultures of stool, urine, blood, throat,
and , if available, sputum should be obtained
Empirical antibiotic therapy should be started
immediately after cultures are obtained
Growth factors that stimulate
granulopoiesis
Cytokine therapy is an adjunctive treatment for
AML
Granulocyte-monocyte colony-stimulating factor
(GM- CSF ) has been used in the
chemotherapy of AML
It increases blast cell proliferation in a proportion
of patients, and this can render the cells more
sensitive to simultaneous or subsequently
administered chemotherapy
This cytokine shortens the duration of neutropenia
by about 3 to 5 days in treated patients
Component transfusion therapy
Red cell transfusion: be used to keep Hb>80g/L
or higher
Platelet transfusion: be used for hemorrhagic
manifestations related to thromocytopenia
Granulocyte transfusion: just in few hospitals
1. Not be used prophylactically for neutropenia
2. Be used in patients with high fever,rigors,and
bacteremia unresponsive to antibiotics,
patients with fungal infections, or patients
in septic shock
Chemotherapy
Remission–inductiontherapy
Remission–maintenance therapy
Remission–induction therapy
Tenet :
1. two competing populations of cells in
marrow: a normal, polyclonal population
and a leukemic, monoclonal population
2. Profound suppression of the leukemic
cells;Restoration of polyclonal
hemopoiesis
Remission–induction therapy
Current standard induction treatment :
1. Daunorubicin plus cytosine
arabinoside ( DA )
2. Homoharringtonine plus cytosine
arabinoside ( HA )
The remission rates: 50%~90%.
The therapy for Acute
promyelocytic leukemia
All-trans retinoic acid (ATRA) has been used
to initiate the therapy for acute promyelocytic
leukemia. The effect of ATRA is to induce
maturation of the leukemic cells and to suppress
the malignant clone, restoring polyclonal
hemopoiesis
Arsenical(As2O3)
The intensive chemotherapy should be used
after remission–induction therapy with all-trans
retinoic acid
Most dangerous and Best Prognosis
Remission–maintenance
therapy
Early intensive consolidation therapy
after remission results in a somewhat
longer remission duration and , more
significantly, a subset of patients who
have a prolonged remission ( > 2 years)
Features influencing outcome of
therapy in AML
B-cell ALL :
HLA-DR , CD19 , CD20
CD10
T-cell ALL : CD7, CD5, CD2
AML: CD13, CD33
Cytogenetic characteristics
Four major groups:
1. Normal karyotype
2. Pseudodiploid
3.Hyperdiploid group I or hyperdiploid
group II
4.Chromosomal translocation
Clinical features
Anemia : pallor , fatigue, weakness,
palpitatioms and dyspnea on exertion
Bleeding
Infection
Pain
Lymphadenopathy and hepatosplenomegaly
Infiltration into other tissues such as skin,
nervous tissue and bone
Laboratory features
Blood cell findings
The total leukocyte count
Anemia
Thrombocytopenia
Borrow
Histochemical analysis
Therapy
Four component to ALL treatment
protocol
1. phase of remission induction
2. Followed by prophylactic treatment of
central nervous system sanctuary area
3. A consolidation or intensification phase
after remission
4.Maintenance or continuation therapy for
a total treatment period of 2 to 3
years
Remission–induction therapy
Current standard induction treatment :
1. Vincristine , Daunorubicin , L-
Asparaginase plus Prednisone (VDLP )
2.
Vincristine , Daunorubicin ,
Cyclophosphamide plus Prednisone
(VDCP)
Consolidation therapy
High-dose methotrexate
Prophylactic treatment of
central nervous system
Intrathecalinjection
methotrexate, hydrocortisone, cytosine
arabinoside
Maintenance therapy
Methotrexate and 6 -mercaptopurine
Chronic myelogenous
leukemia(CML)
Definition
Basophils 3
Eosinophils 2
Nucleated red cells 0.5
Monocytes 8
Lymphocytes 8
Marrow
Ph chromosome, t(9;22)(q34;q11);
Present in all blood cell lineages;
Have the classic Ph chromosome in
about 90% of patients in CML
Chemical abnormalities
1. Uric acid is increased;
2. Serum vitamin B12- binding protein
and vitamin B12 is increased
Therapy
Chemotherapy
Alpha-interferon
Bone marrow transplantation
Glivec
Chemotherapy