بسم ا الرحمن الرحيــــــم Leukemia Course- Lecture #3
ACUTE LEUKEMIAS Akram Al-Hilali 2009
08/06/14
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WHY DOES THE LEUKEMIA ?BEHAVE AS ACUTE Type of oncogene Change in the oncogene Rate of multiplication in the resulting leukemia cells Analogy with benign vs. malignant tumours elsewhere.
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CLASSIFICATION OF ACUTE LEUKEMIAS Original classification by morpholgy in the
Romanowsky and specials stains Presence of intermediate cells. Clinical: Adenopathy, age, gum ulceration, DIC Auer rods in blasts Positive myeloperoxidase or SBB. Positive PAS in blasts. Positive NSE (alpha naphthyl esterase) 08/06/14
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Myeloblast with Auer rod
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M1- Myeloperodxidase
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ALL-PAS
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M5- NSE
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TALL-Acid phosphatase
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CLASSIFICATION OF ACUTE LEUKEMIAS Refined morphologic classification (FAB)
M1 to M7 for myeloblastic Later M0 was added. M3 microgranular variant was then demarcated. M5 divided into A & B L1 to L3 for lymphoblastic
In FAB classification of MDS CMML was one of the conditions and RAEB-T had 2030% blasts. Later RAEB-T was removed in the WHO classification as an entity and considered AML and CMML was added to the combined MDS-MPN group 08/06/14
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AML- M1
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AML-M2
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AML-M3 08/06/14
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AML-M3
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AML- M3 variant
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AML-M4
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AML-M5-A 08/06/14
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AML-M5-B
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AML-M6
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AML-M7
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ALL-L3
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CLASSIFICATION OF ACUTE LEUKEMIA- DEVELOPMENTS Between the FAB classification and the emergence of
WHO classification there have been developments in technology with results being reported on some of the morphologic subtypes in: Chromosomal aberrations and clone with the recurring aberration in the same leukemic type. Inv16 became known before WHO classification. Immunomarkers specific for certain types were being discovered that helped clearly split ALL from AML cases as well as subtypes within each. Later on, detailed gene studies became available, which helped put clones together on a molecular basis, whether or not they had chromosomal change. 08/06/14
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CLASSIFICATION OF ACUTE LEUKEMIAS- Comments
Latest WHO classification More meaningful, both treatment and prognosis-wise. Takes morphology into consideration but depends heavily on immunophenotyping by flowcytometry and molecular changes in genes (by PCR or FISH), with or without gross chromosomal aberrations 08/06/14
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CLASSIFICATION OF ACUTE LEUKEMIAS- highlights Secondary leukemia as a special entity. Acute leukemia arising from MDS Leukemia secondary to chemotherapy and immune suppressive agents. Acute biphenotypic leukemia
This is suspected morphologically in some cases (2 types of blasts or same blasts showing dual morphology) Myeloid lineage confirmed by MPO or monocytic differentiation (NSE, CD11c, CD14, CD64) B lineage confirmed by strong CD19 with one of CD79a, CD22 or CD 10. If CD19 is weak we need 2 of the others. T lineage: cCD3, or sCD3 (rare) 08/06/14
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SOME PROGNOSTIC ELEMENTS IN ACUTE LEUKEMIA Age, gender, leukocyte count at diagnosis and type of leukemia (B-ALL bad, pre-B ALL good) PML: good. Presence of previous MDS and chemotherapy history. Chromosomes: Bad: t(9;22), t(6;9),t(6;11) del5q, complex 3,5,7 karyotype, t(11;19) Good: X or Y abnormalities alone, t(15;17), t(8;21) Inv16 and t(16;16) in AML. Polyploidy in ALL.
Genes: Bad: WT1 mutations, FLT3-ITD, MLL-PTD and KIT in AML and t(9;22) in ALL Good: NPM1 and CEBP-A in AML. 08/06/14
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MANAGEMENT OF AML Chemotherapy combination protocols. Advantage of combined chemotherapy protocols. Induction course, consolidation and intensification
courses. No maintenance therapy. Bone marrow transplantation. Peripheral blood Stem Cell Transplantation Cord Blood Transplantation Non-ablative SC transplantation Donor lymphocyte infusion. Immunotherapy by monoclonal antibodies ATRA as a maturing agent in promyelocytic leukemia Possible introduction of cancer vaccines in leukemias. 08/06/14
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Hb
WBC
Platelets
Transfusions Drugs
1
30 08/06/14
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Days of therapy
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MANAGEMENT OF ALL Induction therapy Followed by maintenance, which may take 2
to 3 years, depending on protocol and type of ALL. Problem of CNS involvement by ALL. Problem of testicular involvement (sanctuary) Stem cell transplantation. Immunotherapy 08/06/14
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