2 BL Acute leukemias Flashcards
Two types of Leukemias
Acute myeloid leukemia (AML)
and
Acute lymphoblastic leukemia (ALL)
ALL demographics
75% of cases of ALL occur in children under 6 years old
Two types of ALL
B-lymphoblastic ALL (B-ALL)
T-ALL
3 types of B-ALL
B-ALL with:
- BCR-ABL1
- MLL
- ETV6-RUNX1
3 types of AML
- Congenital
- Therapeutic
- AML, NOS (not otherwise specified)
5 cytogenic abnormalities for congenital AML
AML with:
- RUNX1-RUNX1T1
- CBFB-MYH11
- PML-RARA (APL)
- RBM15-MKL1
- MLL
2 causes of therapeutic AML
- aklylating agent + radiation
2. topoisomerase II inhibitors
molecular findings leading to AML-NOS
- FLT3 ITD
- NPM1
- CEPBA
“leukemic stem cell” theory
• Theory suggests that chemo only kills differentiating or differentiated cells, so you don’t kill the LSCs. As a result, the cancer can recur.
risk factors for acute leukemia
dont forget: majority of acute leukemias occur in the apparent absence of risk factors
- Previous chemotherapy, especially DNA alkylating agents and topoisomerase-II inhibitors
- Previous exposure of active marrow to ionizing radiation
- Tobacco smoke
- Benzene exposure
- Genetic syndromes (Down Syndrome, Bloom, Fanconi, ataxia-telangiectasia)
signs and symptoms of acute leukemia at initial presentation. What are they due to?
• Signs and symptoms are because normal cells in the marrow are replaced by leukemic cells
○ anemia: fatigue, malaise, pallor, dyspnea
○ thrombocytopenia: bruising, petechiae, hemorrhage
○neutropenia: fever, infections
Rare signs and symptoms of acute leukemia
- Thrombocytic events are due to increased blood viscosity (known as leukostasis and is seen where WBC count is very high)
- DIC can be initiated by some leukemic cells
- Direct infiltration of skin, gums, lymph nodes, and other tissues
ALL and AML generic marker of immaturity
CD34
ALL lymphoblast marker
TdT
- common lymphoblast marker (not on mature lymphocyte)
ALL markers of B cell lineage
CD19,
CD22
ALL markers of T cell lineage
CD3
CD7
B-ALL
- patient age
- sex
- manner of manifestation
- prognosis.
○ Age: more frequent in neonates and young children
○ Sex: Females > Males
○ Manifestation: B-cell lineage antigens, lack CD20 markers of mature B-cells
○ Prognosis: depends
Does B-ALL express CD20?
No.
Not on mature B cells
-express CD19, CD22, CD34
T-ALL
- patient age
- sex
- manner of manifestation
- prognosis.
○ Age: more frequent in adolescents and young adults
○ Sex: Males > Females
○ Manifestation: T-lymphoblastic lymphoma, (mediastinal mass). Elevated WBC.
○ Prognosis:
- adults: complete remission 60-80%; 50% cure
-children: cure rates >95% remission , 80% cure
% of ALL cases. How much B-ALL, how much T-ALL?
B-ALL: 75% of all ALL cases
T-ALL: 25% of all ALL cases
Pt age group of (B-ALL) BCR-ABL1
-prognosis?
25% cases of adult B-ALL, 2% of childhood B-ALL
(more common in adults)
- Ph+: worst prognosis of any ALL!
Pt age group of (B-ALL) MLL
-prognosis?
a. Most common in neonates and young infants
b. Poor prognosis
*MLL of both B-ALL and congenital AML MLL have poor prognosis
Pt age group of (B-ALL) ETV6-RUNX1
-prognosis?
a. 25% of cases of childhood B-ALL
b. Very favorable prognosis!
5 factors affecting prognosis in ALL
- Age
- White blood cell count
- Slow response to therapy / small amounts of residual disease after therapy
- Number of chromosomes
- B versus T lineage
What has worst prognosis, B-ALL or T-ALL?-ALL
B-ALL
What is the prognosis for ALL with regards to hyperdiploidy vs hypodiploidy?
very favorable prognosis for hyperdiploidy (>50 but <46 chromosomes).
2 types of findings that would allow for a diagnosis of AML.
- Increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood
- cytogenetic findings
- CD34 (on myeloblasts)
- CD117 (C-Kit)
- Myeloperoxidase marker
clinical significance of Auer rod
Myeloblasts are very generic looking, can be confused with lymphoblasts unless you see Auer rods!
• Not only does the presence of an Auer rod tell you that you have a myeloblast, it means you have an ABNORMAL myeloblast.
Here are 3/5 cytogenic abnormalities for congenital AML: Prognosis and Pt population?
- RUNX1-RUNX1T1
- CBFB-MYH11
- RBM15-MKL1
- RUNX1-RUNX1T1:
- younger patients
- good prognosis - CBFB-MYH11:
- younger patients
- good prognosis - RBM15-MKL1
- infants with down syndrome
- good prognosis
Here are 2/5 cytogenic abnormalities for congenital AML:
- PML-RARA
- % of AML? - MLL
- prognosis?
- PML-RARA (APL)
- 5-10% of all AML
- prognosis not stated - MLL
- Poor prognosis
- Pt not stated
two reasons why it is important to recognize at initial diagnosis that a case of AML is the AML with t(15;17)(aka acute promyelocytic leukemia (APL)
- Don’t need chemo!
- treat with all trans retinoic acid (ATRA) - APL is associated with DIC
2 main categories of therapy-related AML, and compare their latency and prognosis.
- t-AML secondary to alkylating agents or radiation:
- Latency of 2-8 years from prior treatment
- POOR prognosis
- t-AML secondary to topo-II inhibitors:
- Latency period of 1-2 years from prior treatment
- POOR prognosis
3 molecular markers (abnormalities) currently used to predict prognosis in patients with AML with normal karyotype
- FLT3 - Internal tandem duplication
- Nucleophosmin-1 : NPM1 mut.
- CEBPA mutation
Which of the 3 molecular markers for AML NOS has poor prognosis (driving prognostic factor)?
FLT3
