الاثنين، 8 فبراير 2010

LEUKEMIA'S


Definition:
A heterogeneous group of malignant neoplasm of the precursors of blood cells
resulting in appearance of blastcells in the blood and bone marrow.
Aetiology
It is unknown but theories are implicated:
o Ionizing radiation.
o Drugs and chemicals; prolonged chemotherapy and immunosuppressive agents,
benzene and its derivatives.
o Genetics; familial incidence, chromosomal abnormalities in leukemic patients.
o Retrovirus.
o Immune status; increased incidence of immunosupressed individuals.
Classification:
FAB classification of acute Ieiikemia depending on morphological and cytological
differences..
Now the diagnosis of acute leukemia based on morphology, cytochemistry,
immunophenotyping and cytogentic.
a)Acute lymphoblastic leukemia (ALL):
Cytochemistry: MPO: Negative, PAS : Positive
Immunophenotyping: Bcell marker ( CD19, CD20 and CD22 ),
Tcellmarker ( CD2, CD3, CD5, CD7 )
Cytogentic: t(8;21), t(8;14)
FAB classification
o LI (small homogenous blasts)
o L2 (large heterogeneous blasts)
o L3 (large homogenous blasts).
b)Acute non lymphoblastic leukemia (ANLL)or (AML)
Cytochemistry: MPO: Positive, PAS : Negative
Immunophenotyping: ( CD13, CD33 ) and others
Cytogentic: t(15;17 ) in M3 and other cytogentic abnormalities in diefferent FAB Classification
FAB classification
o Ml: Acute myelobla~tic leukemia without maturation.
o M2: Acute mycloblastic leukemia with maturation.
o M3 :Hypergranular promyelocytic leukemia.
o M4:Myelomonocytic leukemia.
o M5:Monoeytic leukemia.
o M6: Erythroleukemia.
o M7: Megakaryocytic leukemia.
Clinical Features of acute leukemia:
o ALL is common in children while ANLL is common in adults
o It is of acute onset with pallor, fever, various infections.
Bone tenderness.
o Mild hepatosplenomegaly.
o Enlarged lymph nodes (in ALL).
o Infiltration of organs (in M4 and M5).
o Meningeal and testicular infiltration in ALL.
o Symptoms of hyperviscosity (due to increased blasts).
o Bleeding tendency in M3.
Hematological findings:
o Severe anemia (normocytic normochromic).
o WBCs; usually increased, but may be within normal or even below the normal range..
o Blood film; blasts are present or absent as in aleukemic leukemia.
o Thrombocytopenia.
o B.M.; hypercellular and infiltrated with blast cells (>20%).
o Biochemical fmdings:
· Increased serum uric acid.
· Increased serum LDH.
N.B.: By treatment with chemotherapy (< style="font-weight: bold;">Lymphoproliferative Disorders
o It is a group of both malignant ( clonal ) and reactive ( polyclonal ) lymphoid disorders.
o It includes:
1. Acute lymphoblastic leukemia.
2. Chronic lymphocytic leukemia.
3. Prolymphocytic leukemia.
4. Hairy cell leukemia.
5. Plasma cell leukemia.
6. Non Hodgkin's lymphoma.
7. Large granular lymphocytosis.
8. reactive lymphocytosis.
o The above mentioned disorders are either :
1. B – cell disorders.
2. T cell disorders.
3. MK cell disorders.
Chronic lymphocytic leukemia
o Affect older people ( > 50 years old )
o Male predominance.
o Diagnostic criteria :
1. Peripheral blood : absolute lymphocytosis > 5.000 / mm 3 usually > 10.000 /mm 3 .
2. Bone marrow: lymphocytosis > 20% of total bone marrow cells.
3. Mature B – cell markers ( CD19, CD20, and single type light chain ).
4. Express CD5.
5. Certain karyotypic abnormalities.
6. Hairy cell leukemia.
o Age > 50 years.
o Male prodominance.
o Characterized by : splenomegaly / pancytopenia.
Diagnostic criteria :
1. Megaloblastic cell have fine hair – like cytoplasmic projection.
2. Cytochemical stains : tartrateresistant acid phosphatase positive.
3. Clonal disorders of mature B – cell markers ( CD19, CD20, sIg, and its specific
markers CD103 / CD 11c.
Plasma cell dyscrises:
o It is a groupe of disorders characterized by expasion of a single clone of
Immunoglobulin – selecting cells.
o Resultant of increase in serum level of a single homogenous Ig or Ig chain
o It includes:
1. Multiple Myeloma.
2. Solitary Plasmocytoma.
3. Waldenstom's macroglobulinemia.
4. Heavy chain disease.
5. Primary Amyloidosis.
6. Monoclonal Gammopathy of undetermined significance.
Multiple Myeloma
o Criteria for diagnosis of plasma cell myeloma:
1. Major criteria:
· Bone marrow plasmocytosis > 20 % (provided clonal markers either K or L)
· Plasmocytosis on tissue biopsy.
· Monoclonal globulin sipke on serum electrophoresis (> 3.5 gm / l for IgG /
2.0 g / L for IgA and > / g / 24 hrs for kappa or lambda light chain excretion in urine )

o Minor criteria :
· Marrow plasmacytosis 10 – 20 %
· Lytic bone lesion.
· Monoclonal globulin spike less than defined in mejor criteria.
· IgM, IgA or IgG decreased.
Myeloproliferative disorders
o Related hematopoietic stem cell malignancies – classified by lineage as following:
1. Chronic myeloid leukemia ( CML ) predominanthy myeloid.
2. Polycythemia vera ( pv ) predominanthy erythroid.
3. Essential thrombocytobenia ( ET) platelets.
4. Myelofibrosis with myeloid metaplasiafibrosis.
5. Myelodysplasia.
6. Paroxysmal nocturnal hemoglobinurea
7. Dysplastic anemias
o Middle aged – eldery individual
o Chronic process – More indulent than acute leukemia
Chronic myeloid leukemia
Diagnostic criteria:
o Pripheral blood and bone marrow: increased total leukocytic count more than 50.000
with immature myeloid cells, basophilis and eosinophilis
o Decresead leukocytic alkaline phosphatase.
o Unique chromosomal abnormality philadelphia chromosom which is reciprocal
translocation t(9;22) resulting in bcr / ab / gene fusion.
Polycythemia rubera vera:
Increased erythrocyte cell mass lead to increased hematocrit blood volume and blood viscosity
with subsequent thrombotic or hemorrhagic problems.
Primary criteria:
o Increased hemoglobin / Hematocrit 18 gm / d1 in men and 16 gm in women or red
cell mass increase ( > 36 ml / kg in male and > 32 ml / kg in female )
o Normal arterial oxygen saturation.
o Palpable splenomegaly
o No other explenation – renal disease, hypocia, tumours …
Secondary criteria :
o Leukocytosis (> 12.000 / mm 3 )
o Thrombocytosis (> 400.000 / mm 3 )
o Abnormal marrow karyotyping
o Elevoted leukocytic alkaline phosphatase
o Elevoted serum β 12 / transcoblamin
Diagnosis of polycythemia vera is usually mode by presence of all primary criteria with
some of secondary criteria.
Myeloid metaplasia ( myelofibrosis )
o Abnormal stem cells leads to deranged hematopoietic cells (esp. megakaryocytes )
which stimulate fibroblast.
o Originally agnogenic ( etiology unknown ) with myeloid metaplasia ( extramedullary
spleen )
o The natural history is in two phases
· Initial cellular phase
· Progressive bone marrow faliure / fibrosis
o Diagnostic criteria
· Diamorphic blood picture with pancytopenia or not depend on the phase.
· Bone marrow biopsy show increase reticulin and collagen.
· Biggest spleen in medicine.
Essenthial thrombocythemia:
o The increased blood plateletes leads to episodicsymptoms: Bleeding thrombosis,
unrelated or acute leukemia in < style="text-align: center;">

ليست هناك تعليقات:

إرسال تعليق