Leukemia Flashcards
Q18.
ACUTE LEUKEMIAS - CLASSIFIY
Neoplastic proliferation of lympho-, myeloblasts in BM >20% –> peripheral blood
Sudden onset
ALL - Acute Lymphocytic Leukemia
- neopl. prolif of lymphoblasts
- 80% childhood, (usu. aggressive around age 4)
1. B-ALL = most common, dg. TdT +ve for CD10,19,20
- Philadelphia chromosome, t(9;22) –> tyrosine kinase (mainly adults, poor prognosis with translocation)
[- others e.g. t(12;21) more in children, better prognosis]
- good responsive to chemo
2. T-ALL = Tdt +ve for CD2-CD8
- generally presents as a medistinal thymus mass in teenagers, assoc w. lymphobastic lymphoma that can rapidly progress –> T-ALL
AML - Acute Myelogenous Leukemia
- neopl. prolif of myeloblasts
- older 50-60yrs +
1. Acute promyelocytic leukemia
- t(15;17), disruption RAR on chr17 –> blocks maturation/ myeloid differentiation –> accumulation
- give all trans retinoic acid (vitA derivative) - differentiation into e.g. neutrophils (6hrs lifespan)
2. Acute Monocytic Leukemia
- lack MPO
- infiltrates gums - swelling
3. Acute Megakaryoblastic Leukemia
- lacks MPO
- associated with Down’s sy before age 5
Dg. karyotyping tranlocation, Giemsa stain, Auer rods
- -> Bad prognosis - 5yr survival 10-15%
- BM transplantation
Q18.
ACUTE LEUKEMIAS - histo
ALL
- lymphoblasts - 1-2 nucleoli w. clumped chromatin
- cytoplasm - acid-shiff material
AML
- myeloblasts - 3-5 nucleoli w. fine chromatin
- cytoplasm w. azurophilic granules cont. MPO
- MPO (in granulocytes) - myeloperoxidase forms crystal aggregates –> Auer rods
Q18.
ACUTE LEUKEMIAS - clinical features?
Similar for both ALL and AML:
- hypercellular BM, expnasion –> bone pain
- neutropenia –> infection, fever
- thrombocytopenia –> bleeding e.g. petechiae, gums, epistaxis etc.
- erythropenia –> anemia, fatigue
- generalised lymphadenopathy, hepatosplenomegaly
- CNS –> headache, vomiting, paralysis
NB. In AML = rare lymphadenopathy and splenomegaly (less dissemination?, maybe as no prolif in them)
Q18.
WHAT IS MYELODYSPLASTIC SY?
AML may arise from pre-existing dysplasia esp. chemo (alkylating agents) and radiotherapy exposure –> myelodsyplastic sy - usu. cytopenias, hypercellular BM, abnormal cell maturation, blasts >20%
- usu. die from infection/bleeding
Q19.
CHRONIC LEUKEMIAS - CLASSIFY
- Chronic Lymphocytic Leukemia (CLL/SLL) - neoplastic proliferation of mature naive B-cells.
- hypogammaglobinemia, thrombocytopenia, neutropenia, erythropenia - anemia, infection, bleeding..
- lympadeno, HSM
- usu. asymptomatic, non-specific symptoms
- small crowded ly, dark round nucleus, smudge cells on smear, proliferation centers.
- can (precursor) –> e.g. DLBCL
- older patients, 50% with trisomy 12 - Hairy Cell Leukemia
- chronic B cell leukemia, CD19, CD20
- proliferation of B-cells with fine hair-like cytoplasmic projections (blood smear, EM)
- marrow infil, spleen - massive splenomegaly, pancytopenia
- rare lymp/ hepatomegaly
- +ve TRAP, dry tap on BM aspiration
- excellent prognosis (cladribine) - Chronic Myelogenous Leukemia (CML)
- -> a myeloproliferative disorder, proliferation of myeloid progenitor cells
- associated with Philadelphia gene, t(9;22), BCR-ABL fusion –> tyrosine kinase, in pluripotent SC so affects granulocytes, megakary and B/T cells.
- hypercellular BM, leukocytosis, characteristic increase in basophils!
- myeloid lineage affected but mostly granulocytes!
- slow onset.. 3 stages:
1. chronic = non-specific symptoms, can survive w/o treatment for up to 3yrs.
2. accelerating = splenomegaly, anemia, bleeding (thrombocyto) etc.
3. transformation = blast crisis - can progress to acute leukemia… AML (2/3), ALL (1/3) - bad prognosis (younger patients with BM transplant within 1st yr - best)
- less common progress –> BM fibrosis
- 1st line treatment to block TRK activity - imatinib
CML vs leukemoid reaction
- t(9;22)
- increased basophils
- granulocytes = LAP -ve (leukocyte alkaline phosphatase)
