Acute Leukemias and MDS Flashcards

1
Q

Contrast acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in regards to demographics of affected patients, and prognosis.

A

AML: 3 cases/100 K people/per year
Only ~10% of childhood leukemias are AML
AML with t(8;21)- relatively good prognosis
AML with inv (16) or t(16;16)- relatively good prognosis
AML with t(1;22)- relatively good prognosis
AML with abnormalities of 11q23- poor prognosis
Therapy-related AML (T-AML)- very bad prognosis

ALL: 1-5 cases/100K people/per year (75% of cases of ALL occur in children less than 6 yrs old)
B-ALL is the the typical ALL of childhood, B-ALL with t(9:22)– Philadelphia chromosome, has the worst prognosis of any subtype, B-ALL with translocations of 11q23; MLL has a poor prognosis, and B-ALL with t(12l21); ETV6-RUNX1 has a very favorable prognosis.

Factors associated with better prognosis in ALL:
2-10 yoa,
B-lymphoblastic
Hyperdiploidy (51-65)

Factors associated with worse prognosis in ALL: 
Infants
Teens/adults
Very high WBC count
Hypodiploidy (<46)
Slow response to Rx
Min. residual disease
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2
Q

Explain the concept of a “leukemic stem cell”.

A

The differentiation of leukemic cells can lead to a variety of different types of leukemias.

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3
Q

List risk factors for acute leukemia, while recalling that the majority of acute leukemias occur in the apparent absence of risk factors.

A
  • Previous chemotherapy, especially DNA alkylating agents and topoisomerase inhibitors
  • Previous exposure of active marrow to ionizing radiation
  • Tobacco smoke
  • Benzene exposure
  • Genetic syndromes, including Down Syndrome, Bloom syndrome, Fanconi anemia, and ataxia-telangiectasia
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4
Q

List common signs and symptoms exhibited by patients with acute leukemia at initial presentation, and explain the reasons for these findings.

A

S/sx of anemia: fatigue, malaise, pallor, dyspnea

S/sx of thrombocytopenia: bruising, petechiae, hemorrhage

S/sx of neutropenia: fever, infections

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5
Q

List methods for immunophenotyping in acute leukemias (covered in notes for previous Introduction lecture), and list a few basic markers (bolded in notes) that would help to assign blasts to a precursor-B, precursor-T, or myeloid lineage.

A

Use of antibodies to detect whether certain substances are being expressed by cells. In acute leukemia this can be done by flow cytometry and immunohistochemistry.

Genetic markers of immaturity: CD34
Common lymphoblast marker: TdT
Markerts of B cell lineage: CD19, CD22
Markers of T cell Lineage: CD3, CD7

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6
Q

Contrast B-ALL and T-ALL in regards to patient age and sex, manner of manifestation, and prognosis.

A

Compared to B-ALL:

  • T-ALL more frequently occurs in adolescents and young adults.
  • T-ALL more frequently presents with a component of T-lymphoblastic lymphoma (T-LBL), often presents as a mediatinal mass
  • T-ALL is more likely to have a markedly elevated WBC count
  • T-ALL favors males over females.
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7
Q

List 3 commonly observed cytogenetic abnormalities in B-ALL, and recall the usual patient age group and prognosis associated with these abnormalities.

A

B-ALL with t(9:22)– Philadelphia chromosome, has the worst prognosis of any subtype… 25% cases of adult ALL, but 2 % of childhood ALL

B-ALL with translocations of 11q23; MLL has a poor prognosis… frequently seen in neonates and young infants

B-ALL with t(12;21); ETV6-RUNX1 has a very favorable prognosis. …25% of cases of childhood B-ALL.

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8
Q

List 5 factors affecting prognosis in ALL.

A
Age
WBC
T-lymphoblastic vs. B-lymphoblastic
Hyperdiploidy vs hypodiploidy
Slow response to Rx
Min. Residual disease
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9
Q

List 2 types of findings that would allow for a diagnosis of AML.

A

AML is usually diagnosed due to presence of >= 20% myeloblasts

  • Identifying blasts by their morphologic appearance while performing a different count on marrow aspirate smear or peripheral blood smear.
  • Immunophenotyping via flow cytometry on marrow aspirate material or peripheral blood OR IHC on marrow core biopsy.
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10
Q

Recognize an Auer rod, and relate its clinical significance.

A

Some myeloblasts may containe Auer rods, allowing for their identification as myeloblasts by morphology alone.

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11
Q

Recall the associated prognosis for the 5 recurrent cytogenetic abnormalities for AML listed in the notes, and recall their typical patient populations if one is listed.

A

1) AML with t(8;21); RUNX1-RUNX1T1
- 5% of AML cases, younger patients
- relatively good prognosis

2) AML with inv(16) or t(16;16); CBFB-MYH11
- 5-10% of AML cases, younger patients
- relatively good prognosis

3) AML with t(15;17); PML-PARA
- 5-10% of AML cases

4) AML with t(1;220; RBM15-MKL1
- Most often seen in infants with down syndrome
- relatively good prognosis

5) AML with abnormalities of 11q23; MLL
- Poor prognosis

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12
Q

Explain 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)) subtype of AML.

A

1) Patients do not require traditional induction of chemo, can instead be treated with WTRA and arsenic salts (little morbidity, no mortality)
2) APL is often associated with disseminated intravascular coagulation (DIC), can be medical emergency.

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13
Q

Contrast the 2 main categories of therapy-related AML, and compare their prognosis.

A

T-AML b/c of Alkylating agents or radiation:
Latency period of 2-8 years, complex karyotype with whole or partial delations of chromosomes 5 and 7, usually progresses to AML through MDS stage.

T-AML b/c of Topoisomerase inhibitors:
Latency period of 1-2 yrs
Rearrangement of 11q23; MLL
Usually doesn’t progress to AML through MDS stage

BOTH HAVE A VERY BAD PROGNOSIS

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14
Q

List 3 molecular markers currently used to predict prognosis in patients with AML with normal karyotype (lacking recurrent cytogenetic abnormalities), and know which of these “trumps” the other two as a driving prognostic factor.

A

FLT3 Internal Tandem duplication
Nucleophosmin-1 (NPM1) mutation
CEBPA Mutation

FLT3 ITD trumps the other 2 has a driving prognositic factor.

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