Lecture 1: The Leukemias Flashcards
1
Q
How do the cells of acute vs. chronic leukemias differ?
A
- Acute = the cells represent immature precursor cells (blast cells)
- Chronic = the cells are more mature appearing
2
Q
In older patients with mild pancytopenia and macrocytosis what should also be in the differential diagnosis?
A
Myelodysplasia or early AML
3
Q
In acute leukemia (especially ALL) patients often present with what complaint?
A
Bone pain
4
Q
What is Sweet’s Syndrome aka acute febrile dermatosis (AFND); and what is it associated with?
A
- Cutaneous manifestation of AML w/ biopsy demonstrating myeloblasts in the dermis (histiocytic variant of AFND)
- Can be confused with pyoderma gangrenosum
- Tx = management of AML
5
Q
Auer rods are seen as azurophilic rods in the cytoplasm of cells in pt’s with what disorder?
A
AML
6
Q
Gingival hypertrophy is most commonly seen in which variant of AML?
A
The M4 and M5 variants
7
Q
Multiple smudge cells seen on peripheral smear are associated with what condition?
A
CLL
8
Q
What are some of the known risk factors for developing AML?
A
- Exposure to radiation and benzene
- Chemotherapy, especially alkylating agents
9
Q
Radiation is a risk factor for all leukemias except for?
A
CLL
10
Q
When the leukocyte count is very high in pt with AML, the leukemic blasts can occlude the microcirculation leading to respiratory failure and cerebral dysfunction, this is known as what?
A
Leukostasis syndrome
11
Q
How is the diagnosis of AML confirmed?
A
Bone marrow aspiration + biopsy showing >20% blasts
12
Q
Which antigens expressed by myeloblasts can be used as markers for AML?
A
- CD34 (stem cell marker)
- HLA-DR
- CD33 and CD13
13
Q
Which translocation is most frequently observed in children with AML?
A
t(8;21)
14
Q
Most cases of AML with t(8;21) are classied as what type of AML; what is the prognosis in adults and children?
A
- AML w/ maturation
- Favorable prognosis in adults
- Poor prognosis in kids
15
Q
Which genetic abnormality is seen in most causes of Acute Myelomonocytic Leukemia (AMML)?
A
inv(16); some have t(16;16)
16
Q
Which tx do pt’s with AMML due to inv(16) or t(16;16) mutation have a good response to?
A
Intensive Chemotherapy
17
Q
Which secondary mutation seen in AMML due to inv(16) mutations confers a poor prognosis?
A
KIT mutations
18
Q
Recurring translocations involving 11q23.3 are seen in what type of AML; what is the prognosis?
A
Acute MONOcytic leuekmia; assoc. w/ poor outcome
19
Q
FLT3-ITD mutations may occur in any subtype of AML, but are most common in which 2; what is the prognosis w/ this mutation?
A
APL and AML with normal karyotype; poor prognosis
20
Q
Mutations of NPM1 are most often seen in what type of AML; prognosis?
A
- Most frequent in acute monocytic leukemia
- In absence of FLT3 mutations is assoc. w/ favorable prognosis
21
Q
Pt’s with AML require immediate hospitilization for what?
A
- Placement of durable venous access (Hickman catheter, subcutaneous port)
- Initiation of chemotherapy
- Irradiated blood and platelet transfusion support
- If febrile and leukopenic, Abx for presumed infection
22
Q
What is the standard chemotherapy induction regimen for AML?
A
- 3 days of an anthracycline, such as danorubicin or idarubicin
- 7 days of continous infusion of cytarabine (aka Ara-C)
23
Q
Which complication may be seen in some patients during the initiation for AML?
A
Tumor lysis syndrome = abrupt necrosis of a large mass of leukemia cells and release of intracellular contents into circulation
24
Q
After induction therapy for AML, patients with neutropenic fever should receive what therapy; what is done if there is persistent neutropenic fever following therapy?
A
- Should receive broad-spectrum Abx
- If there is persistent neutropenic fever despite Abx this warrants empiric ANTI-FUNGAL therapy
25
Older pt's with AML that have significant comorbidities and high-risk cytogenic abnormalities have lower remission rates and are best treated how?
**Palliatively**, rather than w/ induction chemo
26
In addition to advanced age, poor performance status, and certain cytogenetic abnormalities, what are 2 other asssociations with AML that indicate a poor prognosis?
AML related to **prior cancer chemo** or a **pre-existing myeloproliferative neoplasm** or **dysmyelopoietic syndrome**
27
Describe the induction, consolidation, and maintenance phase of tx for AML?
- **Induction**: **3 + 7 (anthracycline** and **cytarabine** aka **Ara-C)**
- **Consolidation**: high-dose **Ara-C** (**HDAC**)
- **Maintenance**: acute promyelocytic leukemia **only** w/ **ATRA**
28
Describe the induction, consolidation, and maintenance phase of tx for ALL?
- **Induction**: vincristine/prednisone plus others
- **Consolidation**: multiple agents plus **CNS prophylaxis** (MTX or Ara-C)
- **Maintenance**: 6-MP and MTX
29
ALL is a malignancy of B or T lymphoblasts and occurs most commonly in whom?
**Children** although may occur in **adults**, predominantly in **7th decade**
30
Diagnosis of ALL requires what; examination of what is a essential part of the initial diagnostic evaluation?
- Presence of **20% or more lymphoblasts** on **BM exam**
- **CSF examination** for evidence of CNS involvement is essential
31
What are some of the common presenting signs/sx's and complications which may occur with ALL?
- Fatigue + dyspnea + bleeding + infection-related fever
- **LAD** and **hepatosplenomegaly** are commom, and **CNS-involvement** may occur
- **Severe cytopenias** and metabolic derangements due to **tumor lysis syndrome** are **common**
32
What is the most frequent translocation seen with adult ALL?
**t(9;22)**
33
Most cases of adult ALL are of B-lineage and express which markers?
- **CD10+, CD19+, TdT+**
- Frequent **myeloid**-assoc. Ags **CD13** and **CD33**
34
Hyperdiploidy (\>50 and usually \<66 chromosomes) is common in which pt's with ALL?
Children
35
Hyperdiploidy is common in the leukemia cells of ALL, gain of which chromosome is most common?
**Chromosome 21**
36
Hyperdiploidy gain of which chromsome is associated with a good prognosis in ALL vs. gain of which is associated with poor prognosis?
- Gain of chromosomes **4, 10,** and **17** = **favorable prognosis**
- Gain of chromosomes **5** and **i(17q)** = **poor prognosis**
37
The t(1;19) translocation is seen in what?
6% **children** w/ **B-lineage leukemia (ALL)**
38
In ALL due to t(1;19) translocation, what markers are seen in the leukemia cells?
**CD10+**, **CD19+**, **CD34-**, and **CD9+\*\*\***
39
A t(8;14) translocation is seen in what type of ALL; common presentation?
- Seen in **mature B-cell ALL**
- These pt's have **_high_** incidence of **CNS** and/or **abdominal nodal involvement** at **diagnosis**
40
Ph-like ALL is a novel subgroup of **high-risk** ALL characterized by increased expression of what?
**HSC** genes, and similar gene expression profile to Ph-positive ALL
41
Induction therapy for ALL commonly consists of which 4 drugs?
**Anthracycline + Vincristine + L-asparaginase** + a **glucocorticoid**
42
Given the risk for CNS involvement in ALL, how should this be treated?
**Intrathecal chemoprophylaxis** **(MTX** or **Ara-C)** WITH or WITHOUT **crnaial irradiation**
43
Since tumor lysis syndrome is common at diagnosis or shortly after institution of chemotherapy for ALL; all patients should receive what?
**IV hydration therapy** and **Allopurinol**
44
What is the follow-up for pt's with ALL who achieve complete remission following therapy?
Further **intensive chemo** with **multiple agents** for **several months** followed by **2-3 years** of **maintenance chemo**
45
Majority of pt's with CML present in chronic phase of disease and may do well for yeasrs, but if untreated, will invariably transform into what?
**Acute leukemia** (myeloid in **2/3's** and lymphoid in **1/3**)
46
How do pt's with CML most often present?
- **Fatigue + lethargy + low-grade fever** and **weight loss**
- **Splenomegaly** may be **striking!**
- **LAD** is **NOT common**
47
What is seen in the blood and peripheral smear of pt with CML?
- Elevated **blood leukocyte count**
- ↑ **granulocytic cells** in **ALL** phases of development on smear; **myelocytes** and **metamyelocytes** are most often found
48
Which finding on BM exam should make you consider the accelerated or blast phase of CML may be occurring?
When **blasts** represent **\>10% of leukocytes** on **BM exam**
49
How is the diagnosis of CML confirmed?
**Cytogenetic studies** of the **BM aspirate** showing **t(9;22)** or presence of **BCR-ABL** gene via **PCR**
50
How should patients with CML presenting with abdominal pain or discomfort be worked up?
Undergo **ultrasonography** or **CT** to identify **splenomegaly** or **splenic infarction**
51
What is the treatment for CML and for how long?
- **Imatinib**
- **Dasatinib** and **nilotinib** = newer and may be used to **initiate** therapy or in pt's who become **resistant** to **imatinib**
- These drugs are given **indefinitely**
52
When is allogenic BMT an option for CML?
- May be used as **initial therapy** in **very young pt's** w/ CML
- More typically used in pt's showing signs of **resistance** to **tyrosine kinase inhibitors** (i.e., **Imatinib**)
53
What is the follow-up schedule and tests done during the initiation phase and once stable in pt with CML?
- **Typically** every **1-2 weeks** during **initiation** of tx w/ **imatinib**
- Once **stable** blood counts achieved, pt's are followed **every month** to monitor blood counts
54
What type of reduction in BCR-ABL transcripts is needed for the best results in tx of CML?
**4-fold reduction** of BCR-ABL transcripts determined by **quantitative PCR**
55
Which findings during follow-up of pt with CML are signs of accelerate phase or blast crisis?
↑ **leukocyte counts** + **basophilia** + **fever** + **enlarging spleen**
56
Which immune defect is most common in pt's with CLL?
- **Infection** w/ **encapsulated organisms** (i.e., ***S. pneumoniae****)* due to inadequate **B-cell function** or **hypogammaglobulinemia**
- **Cell-mediated** immune defects that predispose to **recurrent herpes simplex virus infections** also may be seen
57
Pt's with CLL are at increased risk for which autoimmune disorders?
Most commonly, **autoimmune thrombocytopenia**
58
In CLL the monoclonal proliferation of B-lymphocytes express which markers?
**CD19** and **CD20**, along w/ expression of **T-lymphocyte Ag CD5**
59
An increase in what helps with the diagnosis of CLL?
Increase in **mature lymphocytes** **\>5000/uL** in the **_absence_** of an **acute viral illness** or other trigger of reactive lymphocytosis
60
Which lab tests are required for diagnosis of CLL?
**Flow cytometry** on a **peripheral blood sample** is **adequate**
61
Using the Rai Staging System for CLL, what is Stage 0 - Stage IV?
- **Stage 0:** lymphocytosis only (ALC \>10,000/mm3)
- **Stage I**: plus **Lymphadenopathy**
- **Stage II**: plus **Hepatosplenomegaly**
- **Stage III**: plus **Anemia** **(Hb \<11 gm)**
- **Stage IV**: plus **Thrombocytopenia** **(\<100,000)**
**\***Remember as **L-L-H-A-T**
62
How is asymptomatic, early-stage CLL treated vs. later-stage disease?
- **Early-stage**: requires only **observation**
- **Late-stage**: required **active tx**
63
What is treatment for pt with CLL who develops autoimmune thrombocytopenia or hemolytic anemia?
**Chemotherapy** for **CLL**, using **prednisone** or **anti-CD20** tx
64
CLL pt's with recurrent bacterial infections should be treated how and all pt's should receive what annually?
- Tx with **IVIG infusion therapy**
- All pt's should receive **annual influenza vaccine** and be vaccinated for **pneumococcal**
65
What are the chemotherapeutic agents which may be used for induction tx of CLL?
- **Purine analogs** (i.e., **fudarabine** and **pentostatin**)
- **Alkylating agents** (i.e., **chlorambucil**, **bendamustine**, and **cyclophosphamide**)
- **Monoclonal Abs** against **CD20** (i.e., **rituximab** and **ofatumumab**)
66
Young patients with CLL and what high-risk genetic factors may be considered for hematopoietic stem cell transplantation?
**17p deletion** or **11q deletion**
67
What is the recommended follow-up for CLL pt's who have not yet required tx or those achieving remission through chemotherapy?
- **Routine monitoring** of the **CBC** every **3-6 months** is recommended to assess **lymphocyte** **count**
- **PE** should include **full LN exam** and careful assessment of **live****r**and**spleen size**
68
Clinical picture of Hairy Cell Leukemia is dominated by sx's related to what?
**Enlarged spleen** and **pancytopenia**
69
Hairy cell leukemia is associated with increased numbers of what in the bone marrow?
**Reticulin fibers**; cause a **"dry tap"**
70
Pt's with hairy cell leukemia have a predisposition to infections by what?
**Atypical mycobacterial infections**
71
Hairy cell leukemia tumor cells express which markers?
**CD22, CD25**, and **CD103**
72
Soluble levels of what antigen from the cells of hair cell leukemia is an excellent tumor marker for disease activity?
**Soluble CD25**
73
Most cases of Hairy Cell Leukemia have what 2 mutations?
Activating **BRAF** mutation **V600E**
74
Median age for hairy cell leukemia is when and what is the male to female ratio?
**Median age = 55 y/o** w/ **M:F** of **5:1**
75
Which tx for hairy cell leukemia has been associated with prolonged remissions?
**Splenectomy**
76
What are some of the chemotherapeutic options for hairy cell leukmia; what are complications of some of these agents?
- **Nucleosides** --\> **Clardibine** and **Deoxycoformycin** = **highly active**, but assoc. w/ **further immunosuppression** and can ↑ risk for **opportunistic infections**
- **IFN-**α is also **effective**, but not as effective as **nucleosides**
77
Hairy cell leukemia which is chemotherapy-refractory may be treated with what?
**Vemurafenib**, a **BRAF inhibitor**
