1
Q
What is chronic lymphocytic leukemia (CLL)?
A
The most prevalent lymphoid malignancy in North America
2
Q
How does the incidence of CLL change with age?
A
It increases with age
3
Q
What is used for the diagnosis of CLL?
A
Flow cytometry demonstrating the presence of clonal B cells with the CLL phenotype
4
Q
What is the iwCLL criterion for the diagnosis of CLL?
A
An absolute B-cell count of at least 5 × 10^9/L
5
Q
What can smaller clones in CLL indicate?
A
Small lymphocytic lymphoma (SLL) if lymphadenopathy is present, or monoclonal B lymphocytosis if not
6
Q
What is monoclonal B-cell lymphocytosis (MBL)?
A
An established pre-CLL condition
7
Q
What risks are associated with MBL?
A
Increased risk of infection and secondary cancers
8
Q
What type of immunodeficiency is associated with CLL?
A
Significant humoral and T-cell-mediated immunodeficiency
9
Q
What is the consequence of immunodeficiency in CLL patients?
A
Increased risk of infection even for untreated CLL
10
Q
Name one class of drugs approved for CLL treatment.
A
Covalent Bruton’s tyrosine kinase (BTK) inhibitors
11
Q
What are the names of three covalent BTK inhibitors approved by the FDA?
A
- Ibrutinib
- Acalabrutinib
- Zanubrutinib
12
Q
What type of BTK inhibitor is pirtobrutinib?
A
A noncovalent BTK inhibitor
13
Q
What is the function of venetoclax in CLL treatment?
A
Inhibitor of BCL2
14
Q
For what types of CLL is venetoclax approved?
A
Both treatment-naive and relapsed CLL in combination with anti-CD20 monoclonal antibodies
15
Q
How is the treatment of relapsed CLL generally determined?
A
Based on which class of agents was used initially
16
Q
True or False: Current data suggest that the sequence of BTK inhibitor then BCL2 inhibitor or BCL2 inhibitor then BTK inhibitor is inappropriate.
A
False
17
Q
What are the two classifications of the same disease related to chronic lymphocytic leukemia?
A
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)
CLL primarily affects blood and bone marrow, while SLL affects lymph nodes.
18
Q
What is the most common leukemia in adults?
A
Chronic lymphocytic leukemia (CLL)
CLL has increasing prevalence due to improved survival with newer therapies.
19
Q
What is the significance of the B cell receptor (BCR) signaling pathway in CLL?
A
It is critical for the biology of CLL and has led to the development of effective therapies.
20
Q
What complications can arise from chronic lymphocytic leukemia?
A
Significant morbidity and mortality due to infections, secondary cancers, and autoimmune complications.
21
Q
What is the prevalence of CLL/SLL in North America and Europe?
A
Most prevalent lymphoid malignancy
It accounts for 25% to 30% of leukemia cases in the United States.
22
Q
What is the incidence of CLL in the United States?
A
4.7 cases per 100,000 persons
18,740 new cases were reported in 2023.
23
Q
What is the median age at diagnosis for CLL?
A
72 years
24
Q
In CLL, what is the sex ratio of incidence?
A
Twice as high in men than in women.
25
What type of malignancy is chronic lymphocytic leukemia?
Indolent malignancy of mature B cells.
26
What is the cell of origin for CLL?
Not fully defined; possibly a hematopoietic stem cell.
27
What does the gene-expression profile of CLL cells suggest?
A common cell of origin for CLL, regardless of somatic hypermutation status.
28
What is the connection between B-1 B cells and CLL?
CLL is most closely related to the CD5+ B-1 B-cell subpopulation.
29
What is the estimated prevalence of CLL in the United States?
207,463 persons.
30
What is known about the etiology of CLL?
The cause remains unknown but there is evidence of genetic predisposition.
31
What populations have the highest risk of developing CLL?
Populations with northern European genetic heritage.
32
What is the increased risk for first-degree relatives of patients with familial CLL?
Approximately 8.5-fold increase in risk of developing CLL or another B-cell malignancy.
33
Is there an indication for screening family members for CLL?
No, because the absolute risk to an individual is still very low.
34
What are some limited environmental risk factors associated with CLL?
Agent Orange, pesticides, and radon exposure.
35
What is monoclonal B lymphocytosis (MBL)?
A precursor to CLL defined as a clonal population of B cells with <5000 clonal B cells per µL.
36
What is the prevalence of MBL in the general population?
15-20%.
37
What defines low-count and high-count MBL?
Low-count MBL: <500 clonal B lymphocytes/μL; High-count MBL: >2000 but <5000 clonal B lymphocytes/μL.
38
What is the risk of developing CLL from high-count MBL?
15% risk of developing CLL over a median of 6.7 years.
39
What is the annual risk of progression to CLL requiring therapy from high-count MBL?
2.9% per year.
40
What risks are associated with high-count MBL?
Risks of bacterial infections and secondary malignancies similar to those of CLL.
41
What is CLL characterized by?
Peripheral blood lymphocytosis, with or without lymph node involvement
42
What is an important driver of CLL survival and growth?
B-cell receptor (BCR) signaling
43
What determines the antigen-binding specificity of BCR?
The composition of the variable regions of the immunoglobulin molecule
44
What percentage of CLL cases share stereotyped BCRs?
~40%
45
In CLL, stereotyped BCRs are primarily found in cases with what mutation status?
Unmutated IGHV
46
What do CLL idiotypic antibodies frequently react to?
Autoantigens, including antigenic targets on apoptotic cells
47
What is a characteristic of CLL idiotypic antibodies?
They tend to be polyreactive
48
What therapeutic targets have been identified in CLL?
The BCR and its signaling pathway
49
What contributes to increased survival of CLL cells in the stromal microenvironment?
Apoptotic defects
50
Which antiapoptotic molecules are important in CLL?
BCL2 and MCL1
51
What is the most common defect detected in CLL by FISH?
13q14 deletion
52
What genes are deleted in the 13q14 deletion in CLL?
Genes coding for the inhibitory microRNAs (miRs) miR15 and miR16
53
What do miR15 and miR16 downregulate in CLL?
Expression of the BCL2 gene
54
What might upregulate BCL2 expression in CLL patients without 13q14 deletion?
miRs, hypomethylation, or other epigenetic regulation
55
What are the effects of CLL cell accumulation in the lymph nodes, spleen, and liver?
Enlargement and disruption of function of these organs
56
What can bone marrow infiltration by CLL cells lead to?
Decreased hematopoiesis and cytopenias
57
What early effect do CLL cells have on normal immune function?
Impaired immunological response to infection
58
What are some constitutional effects of progressive CLL?
Weight loss, drenching night sweats, fevers, and fatigue
59
What likely causes the constitutional effects of progressive CLL?
Dysregulated cytokine production
60
What is the usual presentation for CLL?
Asymptomatic leukocytosis/lymphocytosis or lymphadenopathy/splenomegaly.
61
What percentage of CLL patients have symptomatic disease at diagnosis?
~20%.
62
List some constitutional symptoms of CLL.
* Profound fatigue
* Drenching night sweats
* Fevers
* Involuntary weight loss
63
What is characteristic of CLL cell morphology?
Increased cell-membrane fragility leading to smudge cells.
64
What does the 2022 WHO Classification state about prolymphocytic progression of CLL?
CLL with >15% prolymphocytes in peripheral blood is classified as prolymphocytic progression.
65
What is the significance of higher percentages of prolymphocytes in peripheral blood?
Associated with more aggressive disease.
66
What is required for the diagnosis of CLL via flow cytometry?
Immunophenotypic characterization showing light-chain restriction in B (CD19+) lymphocytes.
67
What are the characteristic immunophenotype features of CLL cells?
* Dim CD20
* Dim light-chain expression
* CD5+
* CD23+
68
What does a negative study result with FMC7 indicate?
Low CD20 expression.
69
What is the minimum clonal B-cell count required for a CLL diagnosis according to iwCLL guidelines?
≥5 × 10^9/L.
70
What is the classification for patients with a clonal B-cell population <5 × 10^9/L?
Small lymphocytic lymphoma variant if lymphadenopathy or splenomegaly is present.
71
What is the role of lymph node biopsy in CLL diagnosis?
Not required but should be performed for low clonal B cell count with palpable lymph nodes.
72
What is a pathognomonic characteristic of CLL/SLL?
Proliferation centers (pseudofollicles).
73
Is a bone marrow biopsy required for CLL diagnosis?
Rarely required; lymphoid tissue is preferred.
74
What is the utility of imaging studies like CT or PET scans in CLL?
Not necessary for most patients; serial imaging is generally not helpful.
75
What is the purpose of clinical staging in CLL?
To classify patients and identify those with advanced-stage disease requiring therapy.
76
What is the median time from diagnosis to first treatment for CLL?
5 to 7 years
77
What is the median survival for patients with CLL?
>10 years
78
What are prognostic markers used for in CLL?
They assist with therapy decisions for patients in need of treatment.
79
What is the most commonly used analysis method for CLL?
FISH
80
What does FISH stand for?
Fluorescence In Situ Hybridization
81
List the currently used genetic profiles in CLL analysis.
* 17p13 (TP53 locus)
* 11q22.3 (ATM locus)
* Trisomy 12
* 13q14 (miR15A and miR16–1 loci)
82
Rank the risk of disease progression based on genetic abnormalities in CLL.
17p13 deletion > 11q22.3 deletion > trisomy 12 > 13q14 deletion
83
What is the role of karyotype analysis in CLL?
It detects chromosomal defects in dividing cells.
84
What indicates a more aggressive disease in CLL according to karyotype analysis?
Complex karyotype (3 or more cytogenetic abnormal findings)
85
What does next-generation sequencing improve in CLL analysis?
Precision of analysis of genetic defects
86
What is the consequence of 17p13 deletion in CLL cells?
Loss of p53 function
87
What percentage of CLL patients with 17p13 deletion have dysfunctional mutations in the remaining TP53 allele?
~80%
88
What is the clinical relevance of BCR signaling in CLL?
Essential for CLL cell survival and proliferation
89
What is IGHV somatic hypermutation associated with in CLL prognosis?
Less aggressive disease and longer survival
90
What defines a patient as having unmutated IGHV?
>98% identity to germ line
91
What is the significance of antigen-binding sites in CLL?
They are important for the selection of CLL progenitor cells.
92
How many major subsets can stereotyped BCR in CLL be classified into?
19
93
What does ZAP70 expression indicate in CLL?
More aggressive disease
94
What is the challenge associated with using ZAP70 as a prognostic factor?
Accurate quantification of intracellular proteins is technically difficult
95
What does higher CD38 levels correlate with in CLL?
More aggressive disease and poorer outcome
96
What is the role of CD49d in CLL?
It is involved in trafficking of hematopoietic cells.
97
What is the association of increased CD49d expression in CLL patients?
Shorter time to first treatment and poorer overall survival
98
What does β2-Microglobulin (B2M) indicate in CLL?
Increased tumor burden and shorter treatment-free survival
99
What is lymphocyte doubling time (LDT) used to estimate?
Time required for a patient's absolute lymphocyte count to double
100
What LDT is associated with poorer prognosis in earlier studies?
<12 months
101
True or False: ALC is a stable parameter in CLL patients.
False
102
What is the main challenge in developing a prognostic examination system for early-intermediate-stage CLL patients?
Rapidly changing understanding of disease biology and limitations of published studies
## Footnote
The indolent nature of CLL also makes clinical studies redundant before completion.
103
What is the significance of TP53 disruption in CLL patients?
Occurs in <10% of patients at diagnosis, but leads to more aggressive disease and poor outcomes
## Footnote
Detected at low frequency with current clinical assays.
104
What is the CLL-International Prognostic Index (CLL-IPI)?
A prognostic model combining genetic, biochemical, and clinical parameters
## Footnote
Developed to improve prognostic accuracy in CLL patients.
105
How many independent prognostic markers for overall survival (OS) in CLL were identified by the CLL-IPI Working Group?
5 independent prognostic markers
## Footnote
These markers can be summed for a risk score.
106
What is the 10-year treatment-free estimate for patients with low-risk disease by IPI?
65.9%
## Footnote
Indicates favorable prognosis for low-risk patients.
107
What is the median time to first treatment for intermediate-risk CLL patients?
52 months
## Footnote
This is longer compared to high-risk and very-high-risk patients.
108
What is the median time to first treatment for very-high-risk CLL patients?
19 months
## Footnote
Reflects a more aggressive disease course.
109
What additional aspect does the CLL-IPI predict apart from time to treatment?
Progression-free survival (PFS) in the setting of treatment
## Footnote
Further validation is needed with patients receiving targeted therapy.
110
What has contributed to the rapid evolution of CLL management in the past decade?
More accurate and earlier diagnosis, better risk stratification, recognition of complications and prevention methods, development of highly effective targeted therapies and immunotherapy.
111
Is there a proven benefit to early treatment of patients with CLL?
No
112
What guidelines are used for the indications for initiating treatment of progressive CLL?
iwCLL guidelines
113
What has transformed the initial therapy for CLL over the past decade?
Shift from chemoimmunotherapy to targeted agents for almost all patients with previously untreated disease.
114
What defines active progressive disease in CLL patients requiring treatment?
Symptomatic disease, rapid disease progression, or bone marrow failure.
115
What precautions should be taken before starting treatment for CLL?
Test for hepatitis B and C infections, consider prophylaxis against herpesvirus and PJP, consider antiviral prophylaxis for patients receiving anti-CD20 monoclonal antibodies.
116
What is the role of prophylactic allopurinol in CLL treatment?
Suggested particularly for patients with a high burden of disease at the start of therapy.
117
What is Bruton's tyrosine kinase (BTK) and its significance in CLL treatment?
Important component of the B-cell receptor signaling pathway; targeted by BTK inhibitors.
118
Name the three BTK inhibitors approved for initial treatment of CLL.
* Ibrutinib
* Acalabrutinib
* Zanubrutinib
119
What is a common effect of BTK inhibitor therapy in CLL treatment?
Early increase in lymphocytosis due to redistribution.
120
What study led to the approval of ibrutinib for frontline treatment of CLL?
RESONATE 2 study
121
What were the outcomes of the RESONATE 2 study comparing ibrutinib to chlorambucil?
Improved progression-free survival (PFS) and overall survival (OS) with ibrutinib.
122
What has long-term follow-up revealed about ibrutinib's PFS?
7-year PFS of 59%.
123
In the A041202 study, what was compared to chemoimmunotherapy?
Ibrutinib alone and ibrutinib plus rituximab.
124
What was the result of the E1912 trial involving ibrutinib plus rituximab?
Prolonged both PFS and OS compared with fludarabine/cyclophosphamide/rituximab (FCR).
125
What was the basis for acalabrutinib's approval for CLL treatment?
ELEVATE TN study
126
What were the PFS results for acalabrutinib plus obinutuzumab compared to chlorambucil plus obinutuzumab?
4-year PFS of 87% for acalabrutinib plus obinutuzumab.
127
What is the significance of zanubrutinib's SEQUOIA trial?
Compared zanubrutinib to bendamustine plus rituximab; showed promising PFS.
128
What are some unique toxicities associated with BTK inhibitors?
* Atrial fibrillation
* Ventricular arrhythmias
* Bleeding
* Hypertension
129
How do the toxicity profiles of BTK inhibitors vary?
Different agents demonstrate different toxicity profiles based on selectivity.
130
What do NCCN guidelines recommend regarding BTK inhibitors?
Acalabrutinib and zanubrutinib as 'preferred' agents; ibrutinib as an 'other recommended regimen.'
131
What is the current treatment paradigm for BTK inhibitors in CLL?
Indefinite dosing.
132
What is venetoclax?
An orally active, targeted small-molecule inhibitor of the antiapoptotic molecule BCL2
133
In the CLL 14 study, venetoclax is administered in combination with which antibody?
Obinutuzumab
134
What is the total duration of venetoclax treatment in the CLL 14 study?
1 year
135
What was compared in the CLL 14 study?
Venetoclax plus obinutuzumab vs chlorambucil plus obinutuzumab
136
What was the outcome of venetoclax plus obinutuzumab compared to chemoimmunotherapy?
Prolonged PFS
137
At 5 years of follow-up, what percentage of patients treated with venetoclax were alive and progression-free?
62.6%
138
What does undetectable minimal residual disease (MRD) indicate?
No CLL can be detected to a depth of <1 CLL cell/10,000 leukocytes
139
What percentage of patients treated with venetoclax plus obinutuzumab showed undetectable MRD?
57%
140
What are the toxicities of concern with venetoclax plus obinutuzumab?
Neutropenia and tumor lysis syndrome (TLS)
141
What is TLS?
Tumor lysis syndrome, a potential toxicity seen with venetoclax or obinutuzumab
142
What is the ramp-up dosing schedule for venetoclax in CLL?
20 mg, 50 mg, 100 mg, 200 mg, and then 400 mg
143
How often does laboratory monitoring for TLS occur during dose escalation?
Predose and postdose
144
Why is chemoimmunotherapy not recommended for most patients with treatment-naive CLL?
Head-to-head comparisons show superiority of targeted agents
145
What is the median PFS for patients with IGHV mutated disease treated with FCR?
14.6 years
146
What are the toxicities associated with FCR?
Short-term myelosuppression, infectious complications, long-term risk of therapy-related MDS/AML
147
For which group of patients is FCR best suited?
Young (≤65 years) and healthy patients with IGHV mutated disease
148
What does MRD stand for?
Minimal residual disease
149
What does the presence of MRD at the end of therapy correlate with?
Shorter PFS
150
What sensitivity do NGS methods offer for MRD detection?
10−6 (or 1/1,000,000 leukocytes)
151
Do current data support using end-of-therapy or midtherapy MRD status to guide treatment decisions?
No, current data do not exist
152
What is the monitoring approach for patients with relapsed/refractory CLL?
Patients can be safely monitored until they meet iwCLL criteria for progressive disease
## Footnote
Monitoring includes assessment of CLL biological risk, disease burden, and screening for hepatitis B and C.
153
Is chemoimmunotherapy recommended for relapsed/refractory CLL?
No, chemoimmunotherapy is not recommended
## Footnote
Alternative therapies should be considered based on prior treatments.
154
What options are available for therapy at relapse for patients who received chemoimmunotherapy as initial treatment?
Any available novel agent
## Footnote
Switching to venetoclax-based therapy is possible if there is disease progression during BTK inhibitor therapy.
155
What can patients who received venetoclax-based therapy as initial treatment switch to at progression?
BTK inhibitor-based therapy
## Footnote
Retreatment with venetoclax can also be considered after a long disease-free interval.
156
What are the covalent BTK inhibitors effective in relapsed/refractory CLL?
Ibrutinib, acalabrutinib, and zanubrutinib
## Footnote
These inhibitors have been studied for their effectiveness in relapsed/refractory disease.
157
What was the outcome of the ELEVATE-RR phase 3 trial comparing acalabrutinib and ibrutinib?
Acalabrutinib showed noninferiority to ibrutinib in terms of PFS
## Footnote
Median PFS for both arms was 38.4 months.
158
What were the findings of the ALPINE study comparing zanubrutinib and ibrutinib?
Zanubrutinib demonstrated superiority in overall response rate and PFS
## Footnote
18-month PFS was 83.3% for zanubrutinib vs. 75% for ibrutinib.
159
What is a common cause of acquired resistance to ibrutinib therapy?
Mutations that prevent ibrutinib from inhibiting BCR signaling
## Footnote
The most common mutation occurs at BTK C481.
160
What mutations are associated with acquired resistance in patients treated with BTK inhibitors?
C481 mutation in BTK and gain-of-function mutations in PLCγ2
## Footnote
These mutations can be detected before clinical progression.
161
What is the significance of pirtobrutinib in treating relapsed/refractory CLL?
Pirtobrutinib is a highly selective noncovalent BTK inhibitor
## Footnote
It has received accelerated FDA approval for patients with prior lines of therapy.
162
What was the overall response rate for pirtobrutinib in the BRUIN study?
73.3%
## Footnote
Median PFS was 19.3 months and activity was independent of BTK mutation status.
163
What is the role of venetoclax in relapsed CLL?
Approved in combination with rituximab based on the MURANO study
## Footnote
Median PFS was 54.7 months.
164
What does PI3Kδ inhibition target in CLL therapy?
Constitutively activated PI3K activity
## Footnote
Inhibition prevents phosphorylation of kinases AKT and mTOR.
165
What are the median PFS results for idelalisib plus rituximab and duvelisib?
15.8 months for idelalisib plus rituximab and 13.3 months for duvelisib
## Footnote
These agents have demonstrated efficacy in relapsed/refractory CLL.
166
What limitations are associated with PI3K inhibitors after novel agents?
Significant toxicity and limited efficacy
## Footnote
These limitations have restricted their usage in current therapeutic approaches.
167
What is CAR-T therapy?
Ex vivo introduction of chimeric genes into autologous T cells using lentivirus vectors
168
Why has the development of CAR-T in CLL been slower than in other lymphoid malignancies?
Due to the inherent immunosuppression observed in CLL
169
What is lisocabtagene maraleucel (liso-cel) approved for?
Relapsed/refractory CLL patients previously treated with a BTK inhibitor and BCL2 inhibitor
170
What study led to the accelerated approval of liso-cel?
Phase 1/2 TRANSCEND CLL 004 study
171
What was the primary endpoint observed in the TRANSCEND CLL 004 study?
Complete response in 18% of patients
172
What was the overall response rate in the TRANSCEND CLL 004 study?
43%
173
How does the duration of response correlate with remission in CAR-T therapy?
Patients who achieve a complete response have a significantly longer PFS than those with a partial response
174
What percentage of patients experienced cytokine release syndrome in CAR-T therapy?
85%
175
What percentage of patients had grade 3 cytokine release syndrome?
9%
176
What percentage of patients experienced neurologic toxicity in CAR-T therapy?
45%
177
What were the grades of neurologic toxicity observed?
18% grade 3 and 1% grade 4
178
What is the goal of ongoing studies regarding CAR-T therapy in CLL?
To define the best product and timing for CAR-T and elucidate which patients are most likely to have long term remissions
179
What is the first effective modality for CLL treatment mentioned?
Reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT)
180
What can restoring immune surveillance in CLL patients lead to?
Long-term disease control and possibly even cure
181
What is the efficacy of RIC allo-SCT in relapsed/refractory CLL?
Effective therapy for patients with very-high-risk disease
182
What is the 5-year PFS range for RIC allo-SCT?
35% to 40%
183
What complication is associated with RIC allo-SCT?
Chronic graft-versus-host disease
184
What is the treatment-related mortality rate for RIC allo-SCT?
~20%
185
In which patients are optimal results of RIC allo-SCT achieved?
Younger and fitter patients with minimal residual CLL who have not had extensive prior therapy
186
Why has enthusiasm for RIC allo-SCT in CLL reduced?
Availability of highly effective targeted small-molecule therapies and alternative immunotherapies
187
Who should be referred for examination at a center specializing in CLL treatment?
Patients with very-high-risk CLL who are candidates for immune therapy
188
What complications are associated with Chronic Lymphocytic Leukemia (CLL)?
Defective innate and acquired immune function, increased risk of infection, autoimmune disease, second malignancy, clonal evolution to aggressive lymphoma (Richter transformation)
## Footnote
Immune dysfunction becomes more severe with disease progression.
189
What major cause of death is associated with patients suffering from CLL?
Serious infections
## Footnote
Infections lead to considerable morbidity.
190
Which types of infections are patients with CLL particularly at risk for due to impaired humoral immunity?
Overwhelming bacterial infections by encapsulated organisms
## Footnote
Examples include Streptococcus pneumoniae and Staphylococcus aureus.
191
What is the consequence of defective T-cell immunity in CLL patients?
Increased risk of herpesvirus reactivation
## Footnote
This includes varicella-zoster virus and herpes simplex virus.
192
What condition can result from reactivation of the varicella-zoster virus in CLL patients?
Shingles
## Footnote
Complications can include postherpetic neuralgia and disseminated varicella-zoster.
193
What reactivation can lead to local lymphadenitis in CLL patients?
Herpes simplex virus reactivation
## Footnote
It may also cause systemic herpes simplex virus infections.
194
In which patients is CMV reactivation more common?
Patients with advanced-stage disease and those treated with lymphotoxic therapies
## Footnote
This increases the risk of serious infections.
195
What type of infections are patients with advanced-stage CLL and those undergoing immunosuppressive therapy at high risk for?
Fungal and atypical bacterial infections
## Footnote
This includes infections associated with BTK inhibitors.
196
What infection has been associated with BTK inhibitors?
Invasive aspergillus infections
## Footnote
BTK plays a role in macrophage activation.
197
What are the recommendations for preventive measures in patients with CLL?
Education, rapid response to infection, vaccination strategies
## Footnote
Patients should be trained to recognize serious infections.
198
What is the general response to vaccination in patients with CLL?
Suboptimal
## Footnote
CDC guidelines should still be followed for vaccination.
199
Which type of vaccines are contraindicated in CLL patients?
Live-virus vaccines
## Footnote
Example: yellow fever vaccine.
200
What is the proven value of prophylactic antimicrobial therapy in CLL?
Not of proven value
## Footnote
However, prophylactic antiviral therapy can be useful.
201
What has been shown to decrease the risk of infections in patients with CLL?
Intravenous immunoglobulin (IVIG) 0.4 mg/kg every 4 weeks
## Footnote
It may not extend overall survival (OS).
202
When should IVIG be considered in CLL patients?
In patients with hypogammaglobulinemia associated with recurrent infections
## Footnote
Subcutaneous formulations are also available for home use.
203
What percentage of patients with CLL have autoimmune complications?
Approximately 5% to 10%
## Footnote
Most autoimmune complications are hematologic in nature.
204
What is the primary cause of autoimmune cytopenia in CLL patients?
Loss of self-tolerance due to disruption of T-cell function by CLL cells.
205
What are the characteristic findings of autoimmune hemolytic anemia (AIHA)?
Reticulocytosis, elevated serum lactate dehydrogenase, indirect bilirubin levels, positive direct antiglobulin test (DAT).
206
What percentage of CLL patients with AIHA have positive DAT results?
>90%
## Footnote
However, only ~15% to 20% of CLL patients develop AIHA.
207
What treatment options are available for patients with AIHA and adequate erythropoiesis?
Immunosuppression using corticosteroids.
208
What additional treatment may benefit patients with severe anemia or slow response to corticosteroids in AIHA?
IVIG (Intravenous Immunoglobulin).
209
What is the effectiveness of splenectomy in CLL-associated AIHA compared to idiopathic AIHA?
Less effective.
210
What condition is suggested by acute-onset or severe thrombocytopenia in CLL patients?
ITP (Immune Thrombocytopenic Purpura).
211
What should be considered in CLL patients presenting with thrombocytopenia without anemia?
Causes of platelet sequestration.
212
What is the recommended management for CLL patients with thrombocytopenia and no bleeding complications?
Careful observation and education.
213
What is a common treatment for patients needing therapy for ITP?
Immunosuppression with corticosteroids with or without rituximab.
214
What is the definitive diagnosis method for autoimmune PRCA?
Bone marrow study showing erythroid-lineage maturation arrest.
215
What is the treatment for autoimmune PRCA?
Immunosuppression using prednisone and cyclosporine.
216
What condition should be considered in patients with isolated neutropenia of uncertain etiology?
Autoimmune neutropenia.
217
What non-hematologic diseases are CLL patients at increased risk for?
Autoimmune-acquired angioedema, paraneoplastic pemphigus, glomerulonephritis.
218
What is the incidence rate of Richter transformation in CLL patients?
~0.5% per year.
219
What are the symptoms that may suggest Richter transformation in CLL?
High LDH, rapid disease progression, constitutional symptoms like weight loss and night sweats.
220
What is the best method for diagnosing diffuse large B-cell lymphoma (DLBCL) in CLL?
Excisional lymph node biopsy.
221
What distinguishes clonally evolved DLBCL from de novo DLBCL in CLL patients?
VDJ rearrangement analysis.
222
What types of skin cancer are CLL patients at increased risk for?
Squamous cell carcinoma, basal-cell carcinoma, melanoma.
223
What should CLL patients be educated about regarding skin health?
Limiting UV radiation exposure and undergoing frequent skin checks.
224
What are the recommendations for CLL patients regarding noncutaneous second malignancies?
Minimize high-risk behavior and follow standard cancer-preventive screening guidelines.
ASH SAP 9 ED
flashcards
Decks in class (17)
# Cards
-
2 Outpatient Hematology104
-
15 Intro VTE228
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23 ITP151
-
27 Laboratory Hematology243
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30 Basics of SCT104
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31 Auto Transplant149
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32 Allo Transplant151
-
33 Adoptive Cellular Therapy83
-
37 MPNs190
-
39 Acquired BMF178
-
40 MDS and CHIP252
-
41 AML129
-
42 ALL104
-
43 Hodkgin Lymphoma131
-
47 CLL224
-
48 MGUS and Myeloma346
-
49 AL Amyloid, Waldenstrom, POEMS152
