BL - Acute Leukemias Flashcards
Demographics & prognosis of affected patients: AML vs ALL
AML: typically a disease of adults. Average age at diagnosis: 65. Heterogeneous prognosis, approximate remission rate of 60%.
ALL: 75% of cases in children < 6 years old. Good prognosis in children, worse prognosis in adults.
Risk factors for acute leukemias
Previous chemotherapy (DNA damaging/alkylating agents, topoisomerase inhibitors), tobacco smoke, ionizing radiation, benzene exposure, genetic syndromes (Down syndrome, Bloom syndrome, Fanconi anemia, AT).
B-ALL vs T-ALL
Compared to B-ALL, T-ALL…
occurs more frequently in adolescents, young adults (B-ALL is the typical ALL of childhood). More frequently presents with mediastinal mass. More likely to have markedly elevated WBC count. Favors males over females. T-ALL has worse prognosis than B-ALL.
3 cytogenetic abnormalities in B-ALL
1) B-ALL with t(9;22); BCR-ABL1. 25% of cases of adult ALL but only 2% of childhood cases. Worst prognosis of any subtype of ALL.
2) B-ALL with translocations of 11q23; MLL. Frequently seen in neonates and young infants. Poor prognosis.
3) B-ALL with t(12;21); ETV6-RUNX1. 25% of cases of childhood B-ALL. Very favorable prognosis.
2 findings that would allow diagnosis of AML
1) >20% myeloblasts in marrow (“packed marrow”) and/or peripheral blood
2) Presence of certain recurrent cytogenetic abnormalities (translocations)
Auer rods
Present in myeloblasts, help to differentiate myeloblasts from other types of blasts. Present in some cases of AML.
Markers to know in AML
Generic markers of immaturity: CD34
Common myeloid markers: CD117 (C-Kit), Myeloperoxidase
Markers to know in ALL
Generic markers of immaturity: CD34
Common lymphoblast marker: TdT
Markers of B-cell lineage: CD19, CD22
Markers of T-cell lineage: CD3, CD7
5 recurrent cytogenetic abnormalities in AML
1) AML with t(8;21); RUNX1-RUNX1T1 – younger patients, good prognosis
2) AML with inv(16) or t(16;16) – younger patients, good prognosis
3) AML with t(15;17); PML-RARA (aka APL) – good prognosis (treat with all-trans retinoic acid and arsenic salts instead of chemotherapies)
4) AML with t(1;22); RBM15-MKL1 – infants with Downs, good prognosis. Shows megakaryoblastic differentiation.
5) AML with abnormalities of 11q23; MLL – poor prognosis
Therapy-related AML (T-AML)
1) from alkylating agents or radiation: 2-8 year latency period. Complex karyotype with whole or partial deletions of 5 and 7. Usually progresses through MDS stage.
2) from topoisomerase inhibitors: 1-2 year latency period. Rearrangement of 11q23 (MLL). Does not usually progress through MDS stage.
**Both have very bad prognosis! Account for 10-20% of cases of AML.
2 reasons it’s important to recognize APL subtype at initial diagnosis
1) Patients can be treated with all-trans retinoic acid and arsenic salts instead of chemotherapies (which can be dangerous/fatal)
2) APL often presents with disseminated intravascular coagulation, which is a medical emergency
3 molecular markers used in AML, NOS
- 1) FLT3 internal tandem duplication (ITD) – poor prognosis
2) Nucleophosmin-1 (NPM1) mutation – if FLT3 ITD negative, good prognosis.
3) CEBPA mutation – if FLT3 ITD negative, good prognosis.
Leukemic stem cell
Has the potential for self-renewal; basically provides an inexhaustible source of leukemic cells in an AML patient – these replace the normal bone marrow.
S/S of patients with acute leukemias
S/S due to decreased numbers of normal cells due to marrow infiltration by leukemic cells. Symptoms: fatigue, malaise, dyspnea, easy bruisability, weight loss, bone pain/abdominal pain, neurologic symptoms. Signs: anemia, pallor, thrombocytopenia, hemorrhage, ecchymoses, petechiae, fundal hemorrhage, fever & infection, adenopathy, hepatosplenomegaly, gum or skin infiltration, renal enlargement/insufficiency, cranial neuropathy
More rare S/S: high white blood cell counts causing hyperviscosity or thrombotic problems.
Markers of B-cell lineage
CD19, CD22
