leukemias Flashcards
acute leukemia main indication
blast/immature cells.
Bone aspirate smear is a must to confirm the diagnosis): >20% blasts in the bone marrow.
in myelogenous leukemia what cells are affected
granulocytes or monocytws
in lymphocytic leukemia what cells affected
lymphocytes are affected
how do u differ btwn chronic and acute leukemias
• By the maturity of cells affected and the rapidity of disease progression:
1-Acute leukemias are characterized by rapid progression and affect immature cells (i.e., immature cells proliferate before maturation)
2-Chronic leukemias progress slowly and affect mature cells
what is a symotom specific for AML
gingival hypertrophy
specific presentation more specific to ALL
testicular enlargement, lymphadenopathy, bone pain
what is the percentage in ppl of ost occurence in acute myeloid leukemia
80% of adult acute leukemias, 20% of childhood (<15 y/o) leukemias
risk factors of acute myeloid leukemia
o Exposure to ionizing radiaAon, previous chemotherapy e.g. alkylaAng agents (secondary AML), exposure to chemicals e.g. benzene o MyeloproliferaAve syndrome o Down syndrome o Viral infecAons
pathogenesis of AML
1.Loss of function of transcription factors needed for differentiation differentiation block.
2.Gain of function mutations of tyrosine kinases =enhanced proliferation
bone marrow biopsy in AML is a defenitive test would show
• >20% myeloid blasts confirms AML
• Checks for Auer rods (needle-like structures in blasts)
Chromosomal abnormaliAes in AML
o t (8;21) - AML1
o t (15;17) - PML/RARA
o Inversion 16 - MYH-11/Cbfb
acute promeolyctic leukemia
• A variant of AML (10-15% of cases) –> cytogeneAcs: t (15;17)
• May present with pancytopenia
• Associated with coagulopathy (DIC) is almost all cases, due to release of procoagulant/profibrinolytic factors from blast cells. (major cause of early death)
• All-trans-reAnoic acid (ATRA) must be combined to the treatment
tx of AML
Chemotherapy, targeted drugs, and bone marrow transplant in severe cases.
what are two main prognostic factors in AML
age
cytogenetics
gd prognostic factors in AML
o Favorable cytogeneAcs: T (15;17), t (8;21), inv (16)
o NPM1 mutaAon with normal FLT3
o De novo disease
poor prognostic factors in AML
o Adverse cytogenetics chromosome 5 del (5q), 7 del, or complex karyotype
o Minimal residual disease posiAvity after chemotherapy
o FLT3 mutation
o Secondary disease e.g. prior MDS or MPN
o Demographics: Age >60, male gender
o High WBC
in lymphoid leukemia there is three types of lymphocytes
- B-cells
- T-cells
- NK cells
what is the commonest type of leukemia in children more males and high risk in down syndrome
ALL
what is the mutation in ALL
A genetic mutation causes uncontrolled growth of lymphoblasts (immature B or T cells).
• These blasts don’t mature or function properly, leading to low normal blood cells and leukemia symptoms.
symptoms of ALL
- Patients present with infections, lymphadenopathy and testicular enlargement and splenomegaly due to extramedullary infiltration), bone pain and arthralgia
- May present with meningeal signs (headache, N/V, visual symptoms; especially in ALL relapse) > CNS disease
ALL -> diagnosis depends on immunophenotyping:
- B-cell: CD19, CD20, CD10, Tdt (terminal deoxynucleo.de transferase)
- T-cell: CD3, CD5, CD7, Tdt
Note: Tdt is found in both B-cells and T-cells, help us to differentiate between myeloid & lymphoid leukemia, bcz Tdt is only found in lymphoblast cells
in chest x ray of ALL
patients with ALL may have a mediastinal mass
ALL prognosis
C. Achievement of first remission: 60-90%
D. Childhood ALL: 75% long-term remission (>5yr) -> better chemo tolerance, lower prevalence of
BCR- Abl fusion gene.
E. Adult ALL: 30-40% 5yr survival
tx of ALL
- Intensive Chemotherapy (Induction Phase)
• Goal: Destroy leukemia cells and achieve remission- CNS Prophylaxis (Prevents Brain Relapse)
• Intrathecal chemotherapy (Methotrexate) injected into spinal fluid - Consolidation & Maintenance Therapy
• Several months to years of lower-dose chemotherapy to prevent relapse - Targeted Therapy (For Specific Mutations)
- CNS Prophylaxis (Prevents Brain Relapse)