nonneoplastic disorders of wbc &...
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NONNEOPLASTIC
DISORDERS OF WBC &
LEUKEMIAS
NONNEOPLASTIC DISORDERS OF
WHITE BLOOD CELLS
The number of leukocytes in the
peripheral circulating blood ranges from
4500 to 11 000/uL
The term leukopenia describes an
absolute decrease in WBC count
NEUTROPENIA
(AGRANULOCYTOSIS)
Neutropenia refers to a decrease in
neutrophils – less than 1500 cells/µL
(norm 1800 - 7700 cells/μL)
Agranulocytosis – a severe
neutropenia - is characterised by
count less than 200 cells /µL
ACQUIRED GRANULOCYTOPENIA
(↓) = NEUTROPENIA
Reduced or ineffective production
(neoplasms involving the bone marrow e.g.
acute leukemias, lymphomas, drugs, aplastic
anemia, chemotherapy, viral infections)
Excessive removal from the blood
(inflammation and infection)
Drugs (idiosyncratic)
Most cases of neutropenia are drug related
The term idiosyncratic is used to describe drug reactions
that are different from the effects obtained in most
people and that cannot be explained in terms of allergy
Many idiosyncratic cases of drug-induced neutropenia
are thought to be caused by immunological mechanisms,
when the drug or its metabolites acting as antigens to
iniciate the production of antibodies react against the
neutrophils
NEUTROPENIA(↓)
DRUG-INDUCED
GRANULOCYTOPENIA (↓)
Cytotoxic drugs use in cancer therapy
Phenotiazin
Thiouracil
Chloramphenicol
Hydantoin derivates
Phenylbutazone
CONGENITAL NEUTROPENIA (↓)
A group of hereditary hematologic disorders,
including:
Cyclic neutropenia (periodic neutropenia that
develops every 21 to 30 days and lasts about 3-6days =
impaired feedback regulation of granulocyte production and
release)
Kostmann’s syndrome (neutrophile count is
less than 200/uL but the total WBC may be within
normal limits. RBC and platelets are normally produced)
ACQUIRED GRANULOCYTOSIS (↑)
Bacterial infections
Malignancy (leukemia = CML)
Tissue trauma
NEOPLASTIC DISORDERS OF
HEMATOPOETIC AND LYMPHOID
ORIGIN
The leukemias, which arise from
hematopoetic precursors in the bone
marrow, can involve lymphocytes,
granulocytes and other blood cells.
Because blood cells circulate throughout
the body, these neoplasms are
disseminated from the onset
LEUKEMIA
Leukemia (from the Greek leukos-
white, and haima blood) is a type of
cancer that usually begin in the bone
marrow and characterized by an
abnormal increase of immature WBC
called “blasts” or mature WBC .
LEUKEMIAS
The leukemic cells spill out into the
blood and infiltrate the liver, spleen,
lymph nodes, and other tissues throughout
the body, causing enlargement of these
organs
Leukemias are more frequent in
adults than in children although
leukemias are the leading cause of death
in children between the ages of 1 and 14.
LEUKEMIA
Leukemia is clinically and
pathophysiologically subdivided into
acute and chronic forms.
ACUTE LEUKEMIA
Acute leukemia is characterized by
rapid increase of immature blood
cells and makes the bone marrow
unable to produce healthy blood cells
(most common in children)
CHRONIC LEUKEMIA
Chronic leukemia is distinguished by
the excessive build up of relatively
mature, but still abnormal WBCs,
Typically taking months or years to
progress. The cells are produced at a
much higher rate than normal
(most common in the elderly)
LEUKEMIAS
Additionally leukemias are subdivided
according to which kind of cell is
affected. This split divides leukemias
into:
• Lymphoblastic or lymphocytic leukemias
• Myeloid or myelogenous leukemias
LEUKEMIA
• The lymphocytic leukemias involve immature lymphocytes and their progenitors that originate in bone marrow but infiltrate the spleen, lymph nodes, CNS, and other tissues
• The myeloblastic leukemias, which involve the malignant transformation of pluripotent hematopoetic stem cell in bone marrow, interfere with the maturation of granulocytes, erythrocytes and thrombocytes.
LEUKEMIAS
Classification
Acute lymphocytic leukemia ( ALL)
Chronic lymphocytic leukemia (CLL)
Acute myeloblastic leukemia ( AML)
Chronic myeloblastic leukemia (CML)
LEUKEMIA- CAUSES
The causes of leukemia are largely unknown
The incidence of leukemia is higher among persons
who have been exposed to:
radiation
benzene
drugs (cyclophosphamide, procarbazin, chloramphenicol)
aggressive chemotherapy (leukemia as a second cancer)
There is also genetic predisposition to develop acute
leukemia incidence among a number of congenital
disorders ( Downe’s syndrome, Fankoni’s anemia)
Acute leukemias can occur within the same family
ACUTE LYMPHOCYTIC
LEUKEMIA (ALL)
• ALLs are consist of a group of neoplasms
composed of immature precursor B or T
lymphocytes. Moste cases (85%) of ALL are
of pre-B-cell origin
• ALL is the most common leukemia in
childhood (80-85% of all leukemias)
ALL
ACUTE MYELOBLASTIC
LEUKEMIA (AML)
• AMLs are an extremely heterogenous group of disorders and compose of immature myeloid cell precursor
• AML is chiefly an adult disease (median age 60-65 years ), however it is also seen in children
AML
ACUTE LEUKEMIAS
• Leukostasis is a condition in which the
circulating blast count is markedly elevated
(usually 100 000 cells/µL)
• Circulating leukemic blasts increase blood
velocity and predispose to development of
thrombosis in small vessels in the
pulmonary (progressive dyspnea) and
cerebral (lethargy, confusion and coma)
circulation
LEUKEMIAS
SYMPTOMS
• Proliferating leukemic cells infiltrate bone marrow,
where they may constitute 60% to 100% of the cells
• The development of other blood cell lines in the
marrow is suppressed
• Anemia ( RBC), Haemorrhagic diathesis ( platelets)
and infections ( granulocytes 500 cells/µL).
• Weight loss, low-grade fever, night sweats (rapid
proliferation and hypermetabolism of lukemic cells)
ACUTE LEUKEMIAS
SYMPTOMS II
Nosebleeds and other type of hemorrhage,
easy bruising (decreased platelet count)
Anemia (weaknes, tachycardia, pallor)
Bone pain (bone marrow expansion by
leukemic cells)
Splenomegaly, hepatomegaly and lymph
node enlargement
Symptoms from CNS ( headache, nausea,
vomiting, seizures and coma - leukemic cells
can cross the blood-brain barrier)
CHRONIC LEUKEMIAS
• In contrast to acute leukemias, chronic
leukemias are malgnancies involving the
proliferation of well-differentiated
myeloid and lymphoid cells
• Two types of chronic leukemias: CLL and
CML
CLL & CML
frequency of morbidity
• CLL is mainly a disorder of old persons (above 50 years; men are affected twice as frequently as women)
• CML accounts for 15% of all leukemias in adults. It is predominantly a disorder of adults between the age of 30-50 years, but it can affect children as well
CLL
CLL is a lymphoproliferative disorder characterized by:
Lymphocytosis (95% of cases – transformation of mature B-
cells; B-cells are immunologically incompetent and don’t respond to antigen stimulation)
Lymphadenopathy (swollen/enlarged lymph nodes)
Splenomegaly (enlarge spleen)
CLL (BLOOD SMEAR)
•
CLL
Infections remain a major cause of morbidity and mortality because of:
• Immunologically incompetent B-cells
• Hypogammaglobulinemia (↓Ig)
Other immunological abnormalities include:
• Autoimmune hemolytic anemia (↓RBC)
• Immune-mediated thrombocytopenia (↓PLT)
CLL - SYMTOMS
Symptoms are related to the progresive infiltration of neoplastic lymphocytes in the
bone marrow and to secondary immunologic defects
Typical symptoms in CLL are: Enlargement of lymph nodes and spleen
Recurent or persistent infections
Anemia ( fatigue, pallor, tachcardia etc.)
Bleeding (low platelets)
Edema
Pain
CML
CML is a myeloproliferative disorder that results
from the malignant transformation of
pluripotent stem cell
CML is associated with the presence of the
Philadelphia chromosome (reciprocal translocation between
the long arm of chromosome 22 and the long arm of chromosome 9)
A new fusion gene on chromosome 22 resulting
in cell growth and proliferation.
Philadelphia chromosome
CML
• In 95% of persons with CML the Philadelfia
chromosome can be identified in granulocytic,
erythroid and megacariocytic precursors as
well as B cells, and some cases T cells
• Although CML originates in the pluripotent
stem cells, granulocyte precursors remain the
dominant leukemic cell type
CML( BLOOD SMEAR)
•
CML - symptoms gradually
exacerbated
Typical CML follows a triphasic course
1. Chronic phase (nonspecific symptoms such as
weakeness, weight loss; laboratory tests: leukocytosis with immature granulocyte in the peripheral blood, anemia and eventually trompocytopenia; 4 years)
2. Short accelerated phase (enlargement of the spleen
and progresive symtoms like low-grade fever, night sweats, bone pain, weight loss, bleeding, easy bruising; 6-12 months)
3. Terminal blast crisis phase (splenomegaly can
increase significantly and symptoms become more pronounced, lab tests – blast counts 100 000/ l; median survival 3 months)