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Hematology, oncology > Acute Lymphoblastic Leukemia (B-cell) > Flashcards

Acute Lymphoblastic Leukemia (B-cell) Flashcards

1
Q

immunophenotypic categories of ALL

A

B-precursor ALL
B-precursor with myeloid features
Mature B cell
T-cell

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2
Q

signs/symptoms

A

painless lymphadenopathy, HSM, painless testicular swelling, constitutional symptoms (fever, fatigue), bruising/bleeding, leukostasis, TLS, mediastinal mass, MSK pain

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3
Q

Variables predicting clinical course of ALL

A

age, immunophenotype, WBC count, genetic aberrations, CNS involvement, response to therapy

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4
Q

General treatment approach of patients less than 70 without major comorbidities who are Ph+

A

induction chemo + TKI’s –> If Cr is achieved, pt undergoes ASCT in first remission followed by consideration for use of maintenance TKI for period of time following allogeneic transplant

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5
Q

Treatment for ALL in general

A

Combination chemotherapy

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6
Q

hyper-CVAD regimen

A

cyclophosphamide, vincristine, doxorubicin (also known by its trade name, Adriamycin), and dexamethasone.

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7
Q

General treatment strategy for PH + ALL

A

Induction with multiagent chemotherapy -and TKI –> once first CR achieved, find HLA matched sibling –> consolidation with allogeneic stem cell transplant

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8
Q

Treatment in general for PH+

A

Multi agent chemotherapy and a BCR/ABL TKI

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9
Q

Major branch point in ALL

A

Presence of philadelphia chromosome (Philadelphia negative or positive ALL)

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10
Q

Why is leucovorin given with MTX?

A

Chemoprotectant – since MTX depletes folic acid in cells, it also targets non-cancerous cells, so leucovorin (reduced folinic acid) is added as a rescue agent 24 hours after methotrexate is given

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11
Q

Why do you need to draw MTX levels on a regular basis?

A

At a specified level, it is safe to stop leucovorin administration

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12
Q

WBC count in b-cell ALL

A

Anything – May be decreased, normal, or very high

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13
Q

Clinical course

A

Variable – can be indolent or aggressive

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14
Q

Diagnosis in general

A
  • Detection of lymphoblasts with characteristic immunophenotype by flow cytometry/IHC
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15
Q

Essential characteristic of B-ALL on flow cytometry

A

Expression of B cell antigens + absence of T cell antigens

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16
Q

What is an immunophenotype?

A

Antigens or markers expressed on cell surface

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17
Q

Characteristic b cell antigens

A

CD19, 22, 79

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18
Q

Prognostic importance of philadelphia chromosome?

A

Used to be considered bad, but don’t really know now that TKI’s are available

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19
Q

Term for quantifying remaining burden of leukemia cells after induction therapy

A

MRD – measurable or minimal residual disease)

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20
Q

Preferred induction therapy regimen

A

No agreed upon standard, center specific. None have been directly compared in prospective RCTs.

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21
Q

Most chemo regimens for ALL contain….

A

Vincristine
steroid
anthracycline
*rituxan if CD20 positive

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22
Q

Prognosis

A
  • Most achieve CR after induction chemo
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23
Q

Definition of CR in ALL

A

Less than 5% blasts from bone marrow and blood + restoration of normal hematopoiesis

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24
Q

Better marker for prognosis than CR

A

MRD

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25
Q

Resistant disease defined as

A

Inability to achieve a CR with initial induction therapy

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26
Q

Workup prior to diagnosis

A
  • Flow cytometry looking for cell markers of precursor B-cell
  • Cytogenetics
  • PCR for BCR-ABL
  • NGS
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27
Q

Demographic incidence

A

bimodal (young patients and older than 45)

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28
Q

B-cell subcategories in ALL

A

Ph-positive, Ph-like, Ph-negative

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29
Q

Therapy is based on

A

1) cytogenetics (Ph+ or Ph like, hypodiploidy, KMT2A-rearrangements) (There are different strategies based on cytogenetics –TKIs only, intensive chemo then transplant)
2) Age (Older than 60, younger than 40)

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30
Q

Management of older patient with ALL

A

Lower intensity chemo

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31
Q

Assessment of Minimal residual disease for PH+

A

PCR for BCR-ABL1

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32
Q

What is Ph-like ALL?

A

Similar gene expression to those of Ph+ ALL but with no BCR-ABL

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33
Q

Concept of Minimal residual disease

A
  • Depth of remission is highly correlated to prognosis . Trumps all other prognostic factors.
  • In patients who achieve MRD, HSCT does not impact outcome.
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34
Q

Agent approved for MRD-positive B-cell ALL

A

Blinatumomab

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35
Q

Severe hypodiploid is associated with what

A

TP53 mutation

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36
Q

Regimens used for young adults in general

A

Pediatric chemo regimens

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37
Q

commonly used ALL regimens

A

1) CALGB (Linker, Larson, ABC regimen) – asparaginase containing
2) Hyper CVAD

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38
Q

Hyper CVAD is

A

cyclophosphamide, vincristine, doxorubicin and dexamethasone (Hyper-CVAD) ***alternating with high-dose methotrexate and high-dose cytarabine
- This regimen includes a risk-stratified schedule of central nervous system prophylaxis with intrathecal methotrexate and intrathecal cytarabine.

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39
Q

Who is transplanted in ALL?

A
  • *Patients with highest relapse risk
    1) Ph+ ALL
    2) MLL (all translocations though t(4:11) the worst
    3) Hypodiploid
    4) ETP (early T-cell ALL)
  • But you have to consider whether MRD negativity trumps decision to transplant
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40
Q

Relapsed/refractory ALL management options

A
  • Transplant
  • Blinatumomab, inotuzomab
  • CAR T-Cell (unknown role at this point)
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41
Q

Blinatumomab mechanism

A

BiTE antibody designed against direct cytotoxic T-cells to CD-3 and CD-19 expressing cancer cells

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42
Q

Induction regimen for most PH negative ALL patients

A

HYPER-CVAD

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43
Q

Consolidation management for most ALL patients

A

Allo transplant

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44
Q

Blinatumomab administration

A
  • 24 hr infusion for weeks in a row (at least 6 cycles, have to be inpatient for first 9 days of treatment)
45
Q

Blinatumomab side effects to know

A

1) CRS

2) Neurotoxicity

46
Q

Major issue for ALL induction therapy

A
  • regimens are highly myelosuppressive, which is why hospitalization is required for blood product support
47
Q

Important complication of asparaginase therapy to be mindful of + why

A

Venous thrombosis (reduces ATIII, protein C and S)

48
Q

class of drug etoposide is in

A

epipodophyllotoxins

49
Q

what is restoration of normal hematopoieisis defined as?

A

25 percent cellularity and normal peripheral blood counts

50
Q

What are the high risk ALL subtypes?

A

1) Ph-like and Ph-positive
2) CNS involvement
3) Burkitt-type

51
Q

ALL and CNS involvement

A
  • ALL has a high risk of CNS involvement, thus all current treatment regimens include CNS prophylaxis
52
Q

Management of CNS involvement with ALL

A
  • whole brain cranial irradiation + at least 6 doses of intrathecal MTX
53
Q

Management of Ph-like

A
  • should be considered for early allo transplant
54
Q

Preferred TKI for PH+ ALL

A

None, choice depends on toxicity profile, comorbidities, and availability (no head to head studies)

55
Q

Preferred TKI per UTD for PH+ ALL

A

Dasatinib (data, some CNS penetration, well-tolerated)

56
Q

TKI duration

A

TKIs are continued through post-remission management

57
Q

Why imatinib is not used

A

less effective than second and third generation TKIs

58
Q

CALGB regimen

A

begins with a cycle of dasatinib plus dexamethasone, followed by systemic and intrathecal methotrexate, and for patients with >20 percent lymphoblasts in bone marrow, vincristine and daunorubicin.

59
Q

Prognostic significance of TEL-AML1

A

good risk

60
Q

Patients with ALL who require CNS prophylaxis

A

ALL patients

61
Q

medications used for CNS prophylaxis with ALL

A
  • methotrexate

- cytarabine

62
Q

clinical significance of CD20 expression in Ph negative ALL

A
  • adverse prognosis
63
Q

High risk features in ALL

A

1) poor cytogenetics
2) elevated white count greater than 30K for B cell or greater than 100K for T cell

64
Q

basic HyperCVAD regimen

A

CVAD alternating with HD-MTX + cytarabine

65
Q

AYA means

A

adolescent and young adult

66
Q

Induction therapy for PH+ ALL under age 65

A 
TKI + vincristine + dex
TKI + multiagent chemo
TKI + steroid
TKI + multiagent chemo
CALGB
blinatumomab + TKI
67
Q

Duration of TKI in maintenance phase

A

At least 1 year

68
Q

Consolidation therapy for PH+ in CR

A

Continue TKI + allotransplant if donor available (in TKI era, still unclear if transplant is needed)
IF donor not available → continue multiagent chemo +TKI

69
Q

BCR-ABL1 transcripts that can be seen in PH+ ALL

A

BOTH p190 and p210

70
Q

PH+ B-ALL markers

A

TdT + Cd25

71
Q

Adverse risk features in ALL

A
  • hypodiploidy
  • KMT2A
  • t(v;14q23)/IgH
  • complex karytoype
  • Ph-like
72
Q

Unique feature of management of patients under 21

A
  • IF they achieve MRD negativity, allo-transplant may not confer any advantage over chemo + TKI, they are not taken to transplant
73
Q

Most common toxicities of asparaginase

A
  • pancreatic (pancreatitis) + hepatic
74
Q

Medication used to treat allergic reactions to pegasparaginase

A
  • Erwinia chrysanthem
75
Q

Best regimen for frail adults

A

TKI + steroid

76
Q

Preferred TKI for hyper-CVAD

A

ponatinib

77
Q

Targeted therapies for anti-CD22

A
  • inotuzumab + blinatumomab
78
Q

blinatumomab mechanism

A
  • anti-CD22 immunoconjugate
79
Q

inotuzumab mechanism

A
  • carries a chemotoxin called calicheamicin (upon internalization, binds to DNA which induces a double-strand DNA break, leading to apoptosis)
80
Q

Blincyto SE’s

A
  • hypotension
  • cytokine release syndrome
  • encephalopathy
  • edema
81
Q

Tisangenlecleucel indication

A

Patients under age 26 with refractory ALL or greater than 2 relapses

82
Q

Refractory or relapse options

A
  • Blinatumomab
  • Allo-HSCT
  • CAR-T cell (kymriah + brexu-cel)
  • inotuzumab (ADC)
83
Q

Management of ALL patient with isolated extramedullary relapse (testicles or CNS)

A
  • systemic therapy (prevent bone marrow relapse)
84
Q

lab results of Ph like

A
  • Philadelphia chromosome negative on cytogenetics

- ABLclass rearrangements (ABL1, ABL2, PDGFRA, PDGFRB, FGFR) on molecular analysis

85
Q

most frequently employed method for MRD assessment

A
  • flow cytometry (specific assays are designed to detect abnormal MRD immunophenotypes), PCR, and NGS
86
Q

basic concept of MRD

A
  • presence of leukemic cells below the threshold of detection by conventional morphologic methods
87
Q

optimal sample for MRD

A

initial pull of bone marrow aspirate

88
Q

management of Ph negative patient is in CR1 but MRD+

A

blinatumomab then transplant (eliminate MRD prior to transplant)

89
Q

Sanctuary sites for leukemic cells

A

CNS + testes (leukemic cells are protected relatively from chemotherapeutic agents)

90
Q

What is the CALGB regimen?

A

Daunorubicin, vincristine, prednisone, pegaspargase

91
Q

What is AYA cancer population defined as

A

Ages 15-39

92
Q

Management of AYA ALL population

A
  • pediatric regimens (CALGB)
93
Q

second line therapy for ALL typically

A

etoposide/ifosfamide/mitoxantrone

94
Q

Side effect to know about with inotuzumab

A
  • severe liver damage (veno-occlusive liver disease)
95
Q

Percentage of hemosiderin laden macrophages among all alveolar macrophages on iron staining from BAL required for DAH diagnosis

A

greater than 20%

96
Q

management of Ph+ ALL patient on TKI with rising BCR-ABL oncoprotein

A
  • ABL1 kinase domain mutation testing (same as for CML patients)
97
Q

First line asparaginase drugs

A
  • pegaspargase
  • calaspargase
  • NOT asparaginase erwinia chrysanthemi (second line)
98
Q

high-risk features of ALL

A

poor cytogenetic features of WBC>30k

99
Q

MRD+ threshold

A

greater than 0.01%

100
Q

HyperCVAD part A? Part B?

A

part A is cyclophosphamide, vincristine, doxorubicin, part B is MTX, cytarabine

101
Q

What is triple IT?

A

steroid + MTX + cytarabine

102
Q

White count denoting high risk ALL

A

50K

103
Q

Management of young, fit person who has PH+ w/ ALL

A

Rituximab and hyper-CVAD (cyclophosphamide, vincristine, adriamycin, and dexamethasone) alternating with high dose methotrexate and cytarabine plus CNS prophylaxis and tyrosine kinase inhibitor

104
Q

PH negative ALL management in older adults with good performance status

A

Inotuzumab ozogamicin + mini-hyper-CVD

105
Q

relapsed refractory options

A

Blinatumomab (blincyto)
If young → CAR-T (kymriah + brexu-cel) then allo-HSCT
IF CD22+ → inotuzumab
Allo-HSCT

106
Q

How is LBL treated

A

Essentially the same as ALL and not like most other aggressive lymphomas

107
Q

What is lymphoblastic lymphoma (LBL)?

A

Extramedullary blast proliferation +/- up to 20% blasts in the bone marrow

108
Q

Most common “PH like” gene rearrangement in ALL patients

A

CRLF2

109
Q
A

Hematology, oncology (218 decks)

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