لخّصلي

Acute leukaemia is a malignant disorder in which haemopoietic blast cells constitute >20% of bone marrow cells.
‏•The primitive cells usually also accumulate in the blood, infiltrate other tissues and cause bone marrow failure.ص
‏CLASSIFICATION
‏•There are two main groups: acute lymphoblastic (ALL) and acute myeloid (myeloblastic) leukaemia (AML).
‏•Rare cases are undifferentiated or mixed.
‏•Subclassification of ALL or AML depends on morphological, immunological, cytochemical and cytogenetic criteria
‏AETIOLOGY AND PATHOGENESIS
‏•The malignant cells typically show a chromosome translocation or other DNA mutation affecting oncogenes.
‏•AML may follow previous myeloproliferative or myelodysplastic diseases.
‏•In some cases of childhood B lineage (common) ALL there is evidence from identical twin studies that the first event, a chromosomal translocation, may occur in utero and subsequent events (e.g. infection) precipitate the onset of ALL.
‏INCIDENCE
‏•Approximately 1000 new cases (20–25/million population) each of AML and ALL per year in the UK.
‏•ALL is the most common malignancy in childhood (peak age 4 years) but also occurs in adults.
‏•AML occurs at all ages but is rarer than ALL in childhood, being most common in the elderly
‏INCIDENCE
‏•Approximately 1000 new cases (20–25/million population) each of AML and ALL per year in the UK.
‏•ALL is the most common malignancy in childhood (peak age 4 years) but also occurs in adults.
‏•AML occurs at all ages but is rarer than ALL in childhood, being most common in the elderly
‏LABORATORY FEATURES
‏•Anaemia, thrombocytopenia and often neutropenia.
‏•Leucocytosis caused by blast cells in the blood usually occurs.
‏•Leucopenia is less frequent.
‏•The bone marrow shows infiltration by blast cells (>20% and often 80–90% of marrow cells).
‏•Coagulation may be abnormal and DIC can occur, especially with AML M3.
‏•Serum uric acid, lactate dehydrogenase (LDH) may be raised.
LABORATORY FEATURES
•Cytogenetic analysis of dividing cells or using the more sensitive fluorescence in situ hybridization (FISH) analysis of dividing or non dividing cells gives diagnostic and prognostic information.
•Cases with normal cytogenetics may be subclassified after DNA analysis into whether or not they show mutations detected only by molecular techniques of genes, e.g. FLT3.
•These mutations also have prognostic significance
TREATMENT
•The first phase of therapy (remission-induction) is with high dose intensive combination chemotherapy to reduce or eradicate leukaemic cells from the bone marrow and re-establish normal haemopoiesis.
•Further therapy is postinduction chemotherapy: this may be intensive (‘intensification’ or ‘consolidation’ chemotherapy) or less intensive (maintenance chemotherapy).
•Each course of intensive treatment typically requires 4–6 weeks in hospital.
TREATMENT
•Remission induction regimes usually comprise an anthracycline (e.g. daunorubicin), cytosine arabinoside (ara-C) and, in some protocols, etoposide.
•Fludarabine combined with high doses of ara-C and granulocyte colony-stimulating factor (G-CSF) (FLAG) may also be used for induction.
•All-trans retinoic acid (ATRA) is given with an anthracycline or arsenic trioxide in acute promyelocytic leukaemia (APML) to induce remission.
TREATMENT
•More than 80% of patients under the age of 60 years achieve remission, defined as a normal full blood count and 85% with two courses.
•Older patients  and those with preceding myelodysplasia or AML secondary to another  disease (e.g. myeloproliferative disorder) have lower remission rates.  
•Two or three further courses are usually given as post-induction therapy  to younger (