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Heme / Onc > SM_270b: Acute Lymphoblastic Leukemias > Flashcards

SM_270b: Acute Lymphoblastic Leukemias Flashcards

1
Q

Describe hierarchy of hematopoiesis

A

Hematopoiesis

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2
Q

T cells mature in the ___

A

T cells mature in the thymus

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3
Q

B cells mature in the ___

A

B cells mature in the bone marrow

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4
Q

Describe antigen expression in normal B cell development

A

Antigen expression in normal B cell development

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5
Q

Describe antigen expression in normal T cell development

A

Antigen expression in normal T cell development

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6
Q

Describe acute lymphoblastic leukemia / lymphoma

A

Acute lymphoblastic leukemia / lymphoma

  • B acute lymphoblastic leukemia / lymphoma: recurrent genetic abnormalities, not otherwise specified
  • T acute lymphoblastic leukemia / lymphoma: early precursor T, others
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7
Q

LBL involves ____, while ALL involves ____

A

LBL involves mass lesion and <25% blasts in bone marrow, while ALL involves > 25% blasts in bone marrow

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8
Q

Describe epidemiology of ALL

A

Epidemiology of ALL

  • Most common cancer of children
  • 85% of ALL are B-ALL
  • Peak incidence of T-ALL/LBL in adolescence
  • Male predominance
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9
Q

ALL is associated with ___

A

ALL is associated with Down syndrome

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10
Q

Describe B-ALL pathophysiology

A

B-ALL pathophysiology

  1. Acquired genetic alterations
  2. Maturation arrest and cell proliferation
  3. Bone marrow replaced by neoplastic lymphoblasts and normal hematopoiesis impaired
  4. Peripheral cytopenia
  5. Lymphoblasts enter blood and infiltrate other organs (spleen, lymph nodes)
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11
Q

Describe B-ALL clinical features

A

B-ALL clinical features

  • Abrupt onset within days to a few weeks
  • Symptoms related to bone marrow failure: anemia, thrombocytopenia, neutropenia
  • B symptoms: fever, night sweats
  • Hepatosplentomegaly, lymphadenopathy, testicular enlargement
  • Bone pain
  • Uncommon CNS involvement
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12
Q

Describe T-ALL / LBL clinical features

A

T-ALL / LBL clinical features

  • High WBC count
  • Anterior mediastinal mass
    • SVC syndrome: pain, dysphagia, dyspnea, or swelling of neck / face / upper limbs due to obstruction of SVC
    • Tracheal obstruction
    • Pericardial and pleural effusion
    • CNS involvement
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13
Q

This is a ___ seen in ___

A

Lymphoblast in ALL

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14
Q

This is ___ seen in ___

A

Hand-mirror cell in ALL

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15
Q

Describe ALL morphology

A

ALL morphology

  • Bone marrow biopsy: hypercellular, sheets of blasts
  • Bone marrow aspirate: increased number of blasts
  • B and T lymphoblasts are morphologically similar
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16
Q

TdT, CD19, and cytoplasmic D3 are markers of ___

A

TdT, CD19, and cytoplasmic D3 are markers of ALL

17
Q

Describe important phenotypic markers of ALL

A

ALL important phenotypic markers

  • Precursor markers: TdT, CD34, CD1a (T cells)
  • B cell markers: CD19, CD10, CD22
  • T cell markers: cytoplasmic CD3, CD1a, CD2, CD5, CD7, CD4 and/or CD8
18
Q

Describe ALL genetics

A

ALL genetics

  • Most cases of ALL have cytogenetic (chromosomal) abnormalities
  • Some recurrent genetic abnormalities define specific subtypes of B-ALL
19
Q

___ typically occurs in infants with ALL

A

KMT2A/MLL translocations t(v;11) typically occurs in infants with ALL

20
Q

___ typically occurs in children with ALL

A

t(12;21) ETV6-RUNX1 typically occurs in children with ALL

21
Q

____ typically occurs in adults with ALL

A

t(9;22) BCR-ABL1 Philadelphia chromosome typically occurs in adults with ALL

22
Q

Describe B-ALL with t(12;21)

A

B-ALL with t(12;21)

  • Fusion of ETV6 with RUNX1 gene
  • Most common genetic lesion in children with B-ALL: 25%
  • Favorable prognosis
23
Q

Describe B-ALL with t(9;22) or Ph+ B-ALL

A

B-ALL with t(9;22) or Ph+ B-ALL

  • BCR-ABL1 fusion gene
  • 25% of adults
  • Poor prognosis: Ph+ has poor prognosis, imatinib improves prognosis
  • Treatment with tyrosine kinase inhibitors
24
Q

Describe B-ALL with t(v;11q23) KMT2A rearranged

A

B-ALL with t(v;11q23) KMT2A rearranged

  • Occurs mostly in infants t(14;11)
  • 60-80% of infants with ALL have translocations involving 11q23.3
  • High WBC counts, organomegaly, CNS involvement
  • Poor prognosis
25
Q

Describe T-ALL genetics

A

T-ALL genetics

  • Abnormal karyotypes in 50-70% cases
  • No major impact on prognosis
  • Most common recurrent cytogenetic abnormalities involves TCR loci (14q, 7p)
  • 50% of cases have NOTCH1 mutations
26
Q

Describe early T-cell precursor ALL

A

Early T-cell precursor ALL

  • Defined by early T cell precursor phenotype
    • Low CD5, no CD1a or CD8
    • Express CD34
    • Express myeloid antigens (no MPO)
  • High risk
27
Q

Survival for children with ALL has ___ over time

A

Survival for children with ALL has improved over time

28
Q

Describe prognosis of ALL

A

ALL prognosis

  • Age at presentation: age < 1 is unfavorable
  • Initial WBC: unfavorable if > 100,000
  • Cytogenetics
    • Favorable: t(12;21), hyperdiploidy
    • Unfavorable: MLL / KMT2A gene, t(9;22) / BCR-ABL1, low hyodiploidy
  • Time to response to inducation chemo: slow response is unfavorable
  • CNS / testicular involvement at initial diagnosis is unfavorable
29
Q

Blinatumomab ____

A

Blinatumomab simultaneously binds to specific molecules on B-ALL cells and T cells, bringing T cells close enough to ALL cells to recognize and kill them

30
Q

This is ___

___ would be a good prognosis

A

B-lymphoblastic leukemia

t(12;21) would be a good prognosis

31
Q

This is ___

Phenotype of abnormal cells is ___

A

T-lymphoblastic leukemia

Phenotype of abnormal cells is cytoCD3+, Tdt+, CD19-, ctoCD22-

Heme / Onc (41 decks)

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