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864 > Hematologic Malignancies Leukemias > Flashcards

Hematologic Malignancies Leukemias Flashcards

1
Q

Chronic Myeloid Leukemia (CML) - Epidemiology

In 2024 estimated 9,280 new cases of CML

Median age of diagnosis: __

More common in ___ (2.5 vs. 1.5)

5-year relative survival: 70%

A

66
men

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2
Q

CML – Pathophysiology

Unregulated myeloid proliferation = excess mature neutrophil production

oncogenic protein resulting in the pathogenesis of CML = ___ chromosome
- ___ active tyrosine kinase
- Increased proliferation of the CML clone
- Decreased apoptosis

A
  • philadelphia
  • Constitutively
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3
Q

CML – Philadelphia chromosome

Breaks in chromosome 9 & 22 = translocate to form BCR-ABL fusion gene
- ___ active oncogene

A

Constitutively

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4
Q

CML – Risk Factors

  • No genetic component identified
  • ___ radiation
  • Atomic ___ survivors
A
  • Ionizing
  • bomb
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5
Q

CML – Presentation

Incidental finding during routine examination or CBC
- Fatigue, Sweating, Bone pain, Weight loss

___ : medical emergency
- As high as 1,000,000 cells/mm3
◦ Risk of leukostasis

A

leukocytosis

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6
Q

CML – Treatment

No treatment, fatal within 5 years

Goals: eradicate leukemic clone with minimal toxicity
◦ Only to cure way is ___ hematopoietic stem cell transplant (HSCT)

Tyrosine kinase inhibitors (TKIs)
◦ Dramatically changed clinical course
◦ Disease control for many years = treat as a chronic disease

A

allogenic

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7
Q

CML

2nd Generation TKIs (3)
- all are approved in first line setting
- faster and deeper response

A

Dasatnib, Nilotinib, Bosutinib

No overall survival advantage when compare to imatinib

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8
Q

CML – Resistance

  • BCR-ABL gene amplification/ overexpression
  • Mutations in the kinase domain
  • Secondary genetic alterations
A

T315I super resistance gene

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9
Q

CML - Asciminib

newest TKI
- Can be used in ___ resistant CML, but study yet to be published on outcome

  • Different dosing for CML CP with and without T315I
    ◦ 40 mg PO BID
    ◦ 200 mg PO BID
A

T315I

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10
Q

TKI DISCONTINUATION CRITERIA

  • No history of AP or BP
  • On TKI therapy for at least __ years
  • Quantifiable BCR-ABL = BCR-ABL < 0.01%(deep molecular response)
  • Stable deep molecular response for > __ years
A

3
2

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11
Q

MONITORING AFTER DISCONTINUATION

  • Quantifiable ___
  • Patient must remain in major molecular response (MMR, BCR-ABL < 0.1%
  • Loss of MMR = restart TKI within ___ weeks
A

PCR
4 weeks

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12
Q

CML – Summary

Translocation between the long arms of chromosomes 9 and 22
- BCR-ABL fusion oncogene (aka Philadelphia chromosome)

Three phases: ___ , ___ , ___

TKIs have revolutionized the treatment and prognosis of CML
- Selection based on patient factors and resistance testing

A

chronic, accelerated, blast crisis

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13
Q

Chronic Lymphoid Leukemia (CLL)

Can convert to an
aggressive lymphoma:
___ transformation

A

Richter’s

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14
Q

CLL – Risk Factors

median diagnosis age: ___

A

old, white, male
70

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15
Q

CLL – Cytogenetics

Del(11q) is associated with extensive lymphadenopathy, disease progression
and shorter median survival
◦ May respond well to fludarabine + alkylating agent

Del( ___ ) is associated with the worst outcomes
◦ Reflects the loss of the key tumor suppressor ___ gene
◦ Short treatment free intervals, poor response to chemotherapy, and short median survival‐

A
  • 17p
  • TP53
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16
Q

CLL – Treatment

Treatment reserved for:
◦ Stage III or IV disease
◦ Clinical symptoms
◦ End organ dysfunction

  • Disease treatment selection is stratified based on cytogenetics and age
  • First line option for all: ___ inhibitors as single agent or chemoimmunotherapy
A

BTK
We do NOT
treat a number!

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17
Q

CLL – Venetoclax

Inhibits BCL-2 resulting in release of BIM and PUMA
◦ BCL-2 is a ___ protein
◦ BIM and PUMA are ___ proteins

A
  • pro-survival
  • pro-apoptotic
18
Q

CLL – Venetoclax & Drug

Interactions!

CYP ___ and ___

A

CYP3A4, P-gp

19
Q

CLL – Relapse or Refractory Disease

Goal of treatment is to ___ symptoms
◦ Current therapies do not cure disease
◦ Patient will ___ after treatment

Management of relapse depends on:
◦ Age and performance status
◦ Previous therapy
◦ Response and duration of response to therapy
◦ Time from last therapy

A

palliate
relapse

20
Q

CLL – Lymphocytosis or Tumor

Flare

Transient increase in absolute lymphocyte count
◦ Associated with ___ , ___ , and ___

Peaks early in treatment course
◦ Resolves by week 12

Does not signify disease progression

A

acalabrutinib, ibrutinib, zanubrtuinib

21
Q

CLL – Summary

Patients with early stage (asymptomatic) disease may only require observation

del( ___ ) is associated with worse prognosis

1st line treatment with
◦ Zanubrutinib/acalabrutinib +/- obinutuzumab (or rituximab) indefinitely
◦ Venetoclax + obinutuzumab x 1 year

Transient ___ may occur with BTK inhibitors

A
  • 17p
  • lymphocytosis
22
Q

AML – Epidemiology

More common in men than women
Median age at diagnosis: __
5-year relative survival
rate: 31.9%
- Highest leukemic deaths in aged 75-84

A
  • 69
23
Q

AML – Pathophysiology

  • Arise from single leukemic cell = expands & acquires additional mutations = proliferation
    resulting in monoclonal population of leukemic cells
  • Failure to maintain balance between ____ and ___
  • Defect in the pluripotent stem cell or a myeloid precursor stem cell
  • Leukemic cells have growth advantage = crowd out normal cells
A

proliferation, differentiation

24
Q

AML – Risk Factors

Secondary AML
- From other disease (i.e. myelodysplastic syndrome)
* Treatment related
* ___ agents
* ___inhibitors

Primary AML
* Genetic predisposition
* Environmental carcinogens

A
  • alkylating
  • Topoisomerase II
25
Q

AML – Presentation

Signs of pancytopenia
- ___ : fatigue, pallor, palpitations
- ___ : infections
- ___: gingival bleeding, ecchymosis, epistaxis

___ pain

___ hypertrophy

A
  • anemia
  • neutropenia
  • thrombocytopenia
  • bone
  • gum
26
Q

AML – Diagnosis

Bone marrow biopsy: greater than ___ % blasts

A

20%

27
Q

AML – FLT3 Mutations

Mutations in the fms-related tyrosine kinase 3 gene (FLT3) are present in 30% of adults with newly diagnosed AML

Cause a factor-independent growth of leukemia cells

Associated with ___ overall prognosis
◦ More aggressive disease
◦ Lower chance of complete remission
◦ Higher rate of relapse

___ can target this mutation: midostaurin, quizartinib, gilteritinib (2nd line only)

A

worse
TKI

28
Q

AML – Treatment

induction
Goal: remission
Consolidation
Goal: prevent relapse

Intensive Induction eligible (7+3)
- Continuous infusion cytarabine + anthracycline
- FLAG-ida +/- gemtuxumab ozogamicin (CD33 + disease)
- Venetoclax + hypo-methylating agent

Intensive induction ineligible
- Venetoclax + hypo-methylating agent
- Hypo-methylating agents; lower dose chemotherapy

Supportive Care
Blood products, prophylactic anti-infectives, hydroxyurea
* Goal: Symptomatic management

A

Intensive Chemotherapy
(7+3)
- cytarabine, idarubicin/daunorubicin

29
Q

AML – Acute Promyelocytic Leukemia (APL)

t(15;17) = PML:RARA
- All trans retinoic acid (ATRA)
- Restores normal maturation/differentiation pathway
- Arsenic trioxide (ATO)

A

Differentiation Syndrome:
* High risk patients can get
prophylaxis with steroids.
Hydroxyurea for treatment
* Signs and sympoms

30
Q

AML – Summary

Diagnosis based on bone marrow biopsy

Treatment divided into induction and consolidation
◦ Induction: induce a complete remission
◦ Consolidation: eradicate residual disease & maintain remission

Low intensity therapy may be an option in those not fit for intense induction chemotherapy

A
31
Q

ALL – Epidemiology

Median age at diagnosis: ___
◦ Most common in ___ , adolescents and young adults aged
15-39 years old
More common in Hispanics and Whites
5-year relative survival rate: 72%
◦ Older age = poorer prognosis
Acute Lymphocytic Leukemia — Cancer Stat Facts

A

17
children

32
Q

ALL - presentation

pancytopenia
ine pain
gum hypertrophy
lympadenopathy
abdominal masses
painless testicular enlargement

A
33
Q

ALL – Diagnosis

Bone marrow biopsy with greater than or equal to ___ % blasts
Classified by:
◦ Type of lymphocyte
◦ Degree of differentiation

A

20

34
Q

ALL – Philadelphia Positive Disease

___ added to multi-agent chemotherapy

A

TKI

35
Q

ALL can hide in sanctuary sites

A

brain and testes

Most protocols include intrathecal chemotherapy!

36
Q

Ph positive: ___ + vincristine + prednisone

Ph negative:weekly ___ + daily 6MP + monthly vincristine (POMP)

A

TKI
methotrexate

37
Q

ALL – HyperCVAD

HyperCVAD
◦ Hyper-fractionated cyclophosphamide
◦ Vincristine
◦ Doxorubicin (Adriamycin)
◦ Dexamethasone

Methotrexate (high-dose) and cytarabine

Intrathecal cytarabine and intrathecal
methotrexate with each cycle

A
38
Q

ALL - Blinatumomab

Bispecific T-cell engager
◦ Fragment of antibody that binds CD19 and CD3

Toxicities very different than standard antineoplastics
◦ Cytokine release syndrome (CRS)
◦ Immune effector cell-associated neurotoxicity syndrome (ICANS)

A
39
Q

Asparaginase

Enzyme that breaks down asparagine (an essential amino acid)
Utilized in many multiagent chemotherapy regimens, but only done in specialized centers and patients are
closely monitored for infusion allergic reactions
3 formulations in clinical use:
◦ PEG
◦ Calaspargase pegol-mknl (Cal-PEG) (1-21 years old)
◦ Erwinia
Unique toxicities:
◦ Hypersensitivity
◦ Anaphylaxis
◦ Pancreatitis
◦ Hemorrhage
◦ Thromboembolism
◦ Hyperglycemia
◦ Hypertriglyceridemia
◦ Hepatotoxicity

A
40
Q

ALL – Relapse/Refractory

Disease

Treatment options:
◦ Consider changing BCR-ABL inhibitor
◦ Clofarabine
◦ Nelarabine (T-cell ALL)
◦ Vincristine sulfate liposomal
◦ Blinatumomab (if not used first line)
◦ Inotuzumab ozogamicin (if not used first line)
◦ CAR-T cell therapy = tisagenlecleucel or brexucabtagene autoleucel
◦ Allogenic stem cell transplant if patients get in to 2nd remission

A
41
Q

ALL – Summary

Risk stratification plays a large role in overall prognosis
Treatment regimens are comprised of an anthracycline, steroid, vincristine, ± pegaspargase
◦ Dose adjusted HyperCVAD or ECOG1910 are 2 protocols used frequently
Maintenance therapy plays a large role in treatment
BCR-ABL is important in therapy selection and overall prognosis. If positive add TKI to treatment

A

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