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Leukemia
Leukemia
About the Disease
Leukemia, lymphoma and myeloma are cancers that originate in the bone marrow (leukemia & myeloma) or in lymphatic tissues (lymphoma).
Different Types of Blood Cancers
Leukemia Non-Hodgkin Lymphoma Hodgkin Lymphoma Myeloma Myelodysplastic Syndromes
What is Leukemia?
Leukemia is cancer found in the blood cells
There are many types of Leukemia
They are classified by how quickly they progress and what type of cell they affect
Leukemia is causes when there is an imbalance of healthy unhealthy blood cells in the body
This occur when one cell awry and the body begins to produce large numbers of this cell
What Is Leukemia?
Cancer of the white blood cells Acute or Chronic Affects ability to produce normal blood cells Bone marrow makes abnormally large
number of immature white blood cells called blasts
What is Leukemia
Greek word which means “white blood” Leukemia is when cells spread rapidly and destroy
living tissue. It grows/invades the bone marrow which is the
factory of blood and replaces normal blood elements with cancer cells.
Cancer cells replace all bone marrow cells which causes infection and bleeding problems.
Leukemia is basically white blood cells that don’t work well and cause trouble.
Continued
Millions of immature and useless white blood cells are produced which makes it harder to kill cancer cells and preserve the good/healthy ones.
Leukemia causes change in cells, DNA, and gene. If the blood matches with donator then you are
curried. Bone marrow is spongy tissue that fills in the center
core of bone. There are 4 different types of Leukemia.
Types of Leukemia
Based on how quickly the disease develops it is classified as either acute or chronic
In Acute Leukemia the white blood cells tend to develop more rapidly and very immature
In Chronic Leukemia the cells tend to develop more slowly
They are also classified by which type of white bloods cells are affected
If the lymphoid cells are affected the disease is referred to as Lymphocytic Leukemia
If the myeloid cells are affected it is called Myelongenous Leukemia
Types of Leukemia
Acute lymphoblastic Leukemia (ALL)
Acute myeloblastic Leukemia (AML)
Chronic lymphocyte Leukemia (CLL)
Chronic myeloid Leukemia (CML)
Demographics of Leukemia Patients (2001 Data)
ALL11%
CLL26%
AML31%
CML15%
others17%
Total Reported Cases = 31,500Sources from Leukemia, Lyphoma, Myeloma Facts 2001
CLL=Chronic Lymphocytic
ALL=Acute Lymphocytic
CML=Chronic Mylogenous
AML=Acute Mylogenous
Chronic and Acute
Chronic Leukemia: Progress slowly (runs a slow course) Not immediately fatal.
Acute Leukemia: Progress rapidly (runs a fast course) Life expectancy short without treatment.
Lymphocyte and Myeloid
Lymphocyte: Increase in white blood cells produced in lymph
nodes and bone marrow. Strikes without any warning.
Myeloid: Increase in white blood cells produced exclusively in
the bone marrow. Strikes without any warning.
Acute Myeloid Leukemia
(AML): Mixed group of disease It means “marrow like” and in this context it
simply means arising from developing blood cells.
This type of leukemia runs a rapid course.
Acute Lymphoblast Leukemia
(ALL): Group of different diseases A complexity of which is still trying to be
unraveled Reached a point where not all are being
treated the same. This type of Leukemia runs a rapid course.
Chronic Myeloid Leukemia
(CML): Characterized by increased production of
granulocytes in the bone marrow. Usually associated with a specific
chromosomal abnormality called the Philadelphia chromosome
Progresses slowly
Chronic Lymphocyte Leukemia
(CLL): This type of cancer is so rare it could be said
not to arise at all in the first two decades of life.
Starts of in the Bone marrow This type of cancer runs a slow course giving
more time to live.
Risk Factors
As of now we do not know the exact cause of Leukemia
Exposure to these have been identified as risk factors
High energy radiation Some genetic syndromes People working with chemical
benzene for a long period of time
Causes
High level radiation/toxin exposure
Viruses
Genes
Chemicals
Mostly unknown
Can’t be caught
Development of Leukemia in the Bloodstream
Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis
Stage 4- Worsening
Stage 5a- Anemia
Stage 5b- Infection
Legend
White Cell
Red Cell Platelet Blast Germ Sources from Leukemia, by D. Newton and D. Siegel
Effects On the Body
Attacks the immune system
Infections
Anemia
Weakness
No more regular white blood cells, red blood cells, and platelets
Blasts clog blood stream and bone marrow
Symptoms
When there are excessive white blood cells --> Infections
When there are few red blood cells: Paleness --> Anemia
When there are few platelets --> Excessive bleeding
Signs Of Leukemia
Most of the symptoms of leukemia are similar to those of a common illness such as the flu. The symptoms will vary according to the type of leukemia.
Tired Frequent infections Easy bruising or bleeding Bone tenderness Headache Enlarged lymph nodes Low red blood count Pale skin Poor appetite
Tests For Diagnosis
Finger prick
Blood sample
Blood dye
Bone marrow sample
Spinal Tap/Lumbar Puncture
Diagnosis
As immature cells increase in the body leads to lower amounts of red blood cells and platelet cells
The low amounts of red blood cells cause patient to be tired and pale
Low amounts of platelet cells cause the patient to easily bruise or bleed
During a physical exam the doctor detects swollen spleen, liver, or lymph nodes
Then there is a blood test conducted to see if it is leukemia The type of Leukemia is determined after bone marrow is
extracted and tested
Diagnosis
Most commonly leukemia is diagnosed by a blood test to count the number of red cells, white cells and platelets. A biopsy of the bone marrow may also be performed
Pictures Of Blood
Normal human blood
White Cell Red Cell
Platelet
Blood with leukemia
BlastsRed Cell
Platelet
White Cell
Sources from Arginine.umdnj.eduSources from beyond2000.com
DiagnosisDiagnosis
Requires all of the following diagnostic components:
a) Documentation of bone marrow infiltration
b) Myeloid origin of the leukemic cellsc) FAB/WHO classification of the
leukemiad) Karyotypic analysis
Differential Diagnosis
chronic myelogenous leukemia
other myeloproliferative disorders
reactive leukocytosis: leukemoid reaction
acute leukemia
Philadelphia Chromosomet(9;22)(q34;q11)
BCR-ABL Gene Product
BCR-ABL p210 Fusion ProteinActivity
Higher tyrosine kinase activity.
– Increases progenitor cells, reduces the pool of
stem cells. Semin Hematol 1988;25:1-19.
– Defective cytoadherence. Hematol Oncol Clin North
Am 1988;12:1-29.
– Suppression of apoptosis. Blood 1994;83:1575-85.
BCR-ABL p210 Fusion Protein
Evidence of its role in CML
In vitro: cause factor-independent,
leukemogenic cell growth in hematopoietic
cell lines.
In vivo: generate in mice CML-like syndrome.
Science 1990;247:824-30.
FAB ClassificationsFAB Classifications
M0: minimally differentiatedM1: without maturationM2: with maturation. May have t(8;21) translocation.M3: promyelocytic. Good prognosis. Can be associated
w/ t(15;17).M4: myelomonocytic; assoc. w/ t(16;16) or inv(16)
(p13q22).M5: monoblasticM6: erythroleukemiaM7: megakaryoblastic. Poor overall survival.
Clinical Course
Median survival: 3.5~8 yr. Chronic phase: 3~4 yr. Accelerated phase (15%): 3~6 mo, then enters acute
phase. Acute phase (blast crisis), 25% in each year,
findings: blasts > 30%, cytogenetic changes other than Ph chromosome, progression likes acute leukemia. 70% enters AML, 30% ALL.
PrognosisPrognosis
“Good risk”: favorable karyotype, including t(8;21), t(15;17), inv(16)/t(16;16)/del(16q) or FAB subtype M3
“Poor risk”: adverse karyotype or resistant disease after first course of chemo (i.e. >15% blasts in post-tx bone marrow bx)
5-yr survival for good, standard, and poor risk patients 70, 48, and 15% respectively. Relapse rates are 33, 50, and 78% respectively.
Treatment
As of yet there is no cure for Leukemia
Many advances have been made in the past couple years
The survival rate of children with Acute Lymphocytic is around 82%
Treatments include: Chemotherapy Radiotherapy Immunotherapy Bone marrow transplant
Research
New drugs
Cord blood and planceta
Treatment
Depending on the type of cancer treatments may vary. Treatments of leukemia may include chemotherapy, radiation therapy, or bone marrow transplant. They also treat leukemia patients with the infusion of healthy blood cells and platelets. During and after the treatment blood counts are done to see if the patient is being controlled or in remission.
Treatments
Blood and marrow stem cell transplantation. Research. Development of new drugs. Immunotherapy. Vaccines. Reversal of multidrug resistance. Gene therapy.
Management (1)
Chronic phase– Hydroxyurea or busulfan, relieves symptoms and
control of disease.
– Interferon-: 20% cytogenetic response, prolongation of survival. . It can gain 20 more months survival than C/T. This advantage must be weighed against its significant side effects.
Management (2) BMT or PBSCT
Allogeneic bone marrow transplantation in the chronic phase is the only therapy known to cure CML 5YS > 50%, relapse < 20%, 20~40% BMT related death in the first year.
It should be done as soon as possible for patients – Chronic phase.– <50 years old.– Has an HLA-identical sibling.
Management (3)STI571
STI 571:Inhibitors of the BCR-ABL fusion proteins (tyrosine kinase)
After six months of therapy with Glivec (STI571), preliminary findings showed that half of 290 patients tested were improving. They had what's known as a cytogenic remission -- a reduction in the 'Philadelphia Chromosome' which causes the disease.
"In these patients we found a very high response rate, there was some response seen in 91 percent of the patients," said Dr. Talpaz of the M.D. Anderson Cancer Center. "Some of the patients returned to the chronic phase of the disease."
Allogeneic Stem Cell Transplantation
eradicates of the marrow cells (marrow-ablating C/T or R/T)
implantation of allogeneic stem cells homing of the stem cells to the marrow cavity growth of the stem cells and recovery of the
blood cells
Complications of SCT
rejection, graft failure graft-versus-host disease infection VOD obliterative bronchiolitis sepsis relapse of disease
GVHD (Graft versus Host Disease)
Immunologic reaction of donor lymphocytes to “foreign” antigens present on the surface of host cells
“foreign” antigens:– HLA antigens– “minor” antigens not detected by current typing
techniques
Acute GVHD (1) incidence
Within the first 3 months after BMT
20~50% of HLA-identical, 80% of HLA non-
identical recipients
incidence increases with
– patient age
– degree of HLA disparity
Acute GVHD (2)manifestations
Histology: lymphocytic infiltration of the epidermis and GI tract
fever dermatitis: diffuse macular dermatitis, bullas,
desquamation enteritis: cramping abdominal pain, watery to bloody
diarrhea hepatitis: jaundice, cholestasis, hepatocellular
necrosis infection: frequently related to mortality hyperacute GVHD (no prophylaxis): 7 days after BMT:
exfoliative dermatitis, shock, hyperpyrexia
Chronic GVHD (1) incidence
develops > 3 months after BMT
20~50% of allografts, usually following acute
GVHD
20~30% develops de novo, without prior
acute GVHD
Chronic GVHD (2) manifestations like collagen diseases
skin: pigmentation, sclerosis mucosa: lichenoid oral plaque, esophagitis,
polyserositis, oral and eye sicca syndrome liver: elevated ALP and GOT in 90% cases chronic wasting due to anorexia chronic pulmonary disease: 10~20% (diffuse interstitial
pnuemonitis and obliterative bronchiloitis)
death usually caused by infection, low mortality related to de novo onset & less tissue involvement.
Blast Crisis
30% ALL, 70% AML
Treatment likes de novo acute leukemia with poor
success.
Chance of achieving remission is possible in ALL,
which may last 4~8 months, but low in AML.
Survival is usually 2~4 months.
CML in Blast Crisis