1
Q
A
2
Q
Incidence of acute lymphoblastic leukemia (ALL)?
A
~50 cases per million per year
3
Q
Most common malignant disease in childhood?
A
Acute lymphoblastic leukemia (ALL)
4
Q
Peak age of incidence for ALL?
A
1–4 years (especially 2–5 years)
5
Q
What happens to WBCs in ALL?
A
They increase markedly (can exceed 100,000/µL)
6
Q
Definition of hyperleukocytosis?
A
Leukocyte count >100,000/µL
7
Q
What macroscopic appearance can blood have in severe leukocytosis?
A
Thick, whitish blood (“white blood”)
8
Q
What are the three layers after blood centrifugation?
A
Plasma – Buffy coat – Erythrocytes
9
Q
What is the buffy coat?
A
Layer containing leukocytes and platelets
10
Q
What happens to the buffy coat in leukemia?
A
It becomes thick and prominent
11
Q
What complication can severe hyperleukocytosis cause?
A
Increased blood viscosity and capillary blockage
12
Q
Why is hyperleukocytosis dangerous?
A
Oxygen cannot adequately reach vital organs due to capillary obstruction
13
Q
Emergency management of severe hyperleukocytosis?
A
Immediate filtering intervention (leukapheresis)
14
Q
What is the cell of origin in leukemia?
A
Hematopoietic stem cell or progenitor cell
15
Q
Difference between lymphoblastic and myelogenous leukemia?
A
Lymphoblastic affects lymphoid progenitors; myelogenous affects myeloid progenitors
16
Q
Difference between acute and chronic leukemia?
A
Acute = rapid progression; Chronic = slow progression
17
Q
First diagnostic step for leukemia?
A
Bone marrow aspiration
18
Q
Where is bone marrow aspiration usually performed?
A
Posterior superior iliac crest (sometimes sternum)
19
Q
What is performed in addition to bone marrow aspiration?
A
Bone marrow biopsy
20
Q
Historical contribution of Farber?
A
Introduced antifolate therapy (aminopterin) targeting folate metabolism
21
Q
Why do antifolates work in leukemia?
A
They block folate metabolism, inhibiting DNA synthesis in rapidly dividing cells
22
Q
Examples of modern chemotherapy agents in ALL?
A
Methotrexate and other antimetabolites; anthracyclines like doxorubicin
23
Q
How has survival in ALL changed over decades?
A
From ~10% in the 1960s to >90% today
24
Q
What percentage of leukemia cases are due to genetic predisposition?
A
~90%
25
Are most leukemia cases directly inherited from parents?
No, most are due to spontaneous mutations during fetal development
26
What percentage of leukemia cases are related to environmental factors?
~10%
27
Examples of environmental risk factors for leukemia?
Solvents, radiation, tobacco smoke
28
How does Down syndrome affect leukemia risk?
Increased risk of ALL
29
How is prognosis in ALL patients with Down syndrome?
Worse prognosis and increased vulnerability to treatment toxicity
30
What is the main pathophysiologic event in leukemia?
Bone marrow is replaced by malignant cells
31
What happens to normal hematopoiesis in leukemia?
It is suppressed due to marrow infiltration
32
Main cause of anemia in leukemia?
Reduced RBC production from marrow replacement
33
Clinical consequence of anemia in leukemia?
Weakness and fatigue
34
Cause of thrombocytopenia in leukemia?
Reduced platelet production from marrow infiltration
35
Clinical consequence of thrombocytopenia?
Spontaneous bleeding and easy bruising
36
Why are leukemia patients prone to infections?
Functional immunosuppression due to abnormal WBCs
37
Why can bone pain occur in leukemia?
Marrow expansion and infiltration
38
Why can leukemia be misdiagnosed as a rheumatic disease?
Bone and joint pain may mimic rheumatologic conditions
39
What is the purpose of flow cytometry in leukemia?
To diagnose and classify leukemia
40
Basic principle of flow cytometry?
Cells are labeled with fluorescent antibodies against surface markers and analyzed by laser detection
41
What happens if a cell expresses the target antigen in flow cytometry?
It fluoresces under laser detection
42
B-cell markers in ALL?
CD19, CD20, CD22
43
T-cell markers in ALL?
CD3, CD4, CD5, CD7, CD8
44
Why are immunophenotypic markers important?
They determine prognosis and guide treatment
45
What is the purpose of cytogenetic testing in leukemia?
To detect chromosomal alterations
46
Example of favorable cytogenetic abnormality in ALL?
t(12;21)
47
What is the purpose of molecular testing in leukemia?
To monitor treatment response and minimal residual disease
48
First phase of ALL treatment?
Induction therapy
49
Goal of induction therapy?
Achieve complete remission
50
What characterizes induction therapy?
Highly intensive initial treatment phase
51
Second phase of ALL treatment?
Consolidation therapy
52
Goal of consolidation therapy?
Destroy remaining leukemic cells and prevent relapse
53
Third phase of ALL treatment?
Re-induction therapy
54
Goal of re-induction therapy?
Reinforce remission
55
Fourth phase of ALL treatment?
Maintenance therapy
56
Characteristics of maintenance therapy?
Low-intensity long-term treatment
57
Duration of maintenance therapy in ALL?
Approximately 1.5–2 years
58
Goal of maintenance therapy?
Sustain remission and prevent relapse
59
Why is intrathecal therapy used in leukemia?
To prevent or treat CNS involvement
60
Why can't standard chemotherapy protect the CNS?
Most chemotherapeutic agents cannot cross the blood-brain barrier
61
How is intrathecal therapy administered?
Directly into the CSF via lumbar puncture
62
What drugs are commonly used intrathecally?
Chemotherapy agents ± steroids
63
Why are high-risk leukemia patients closely monitored after intensive treatment?
Increased risk of complications and toxicity
64
Static prognostic factors in leukemia?
Age, gender, initial blast count, cytogenetic profile
65
Dynamic prognostic factor in leukemia?
Response to treatment (e.g., minimal residual disease)
66
Cell of origin in Acute Myelogenous Leukemia (AML)?
Myeloid precursor cell
67
What determines AML classification?
Morphology, cytogenetics, and molecular testing
68
Why is cell morphology important in AML?
It guides diagnosis and prognosis
69
Examples of AML subtypes based on morphology?
Myelomonocytic, monocytic, erythroleukemia, megakaryoblastic leukemia
70
What is Acute Promyelocytic Leukemia (APL)?
A subtype of AML characterized by promyelocyte proliferation
71
Why is APL considered a fulminant leukemia?
Rapid progression with high risk of severe coagulopathy
72
Life-threatening complication of APL?
Severe coagulopathy leading to hemorrhage
73
Genetic abnormality in APL?
Translocation t(15;17)
74
What fusion gene is formed in APL?
PML-RARα
75
What is the consequence of the PML-RARα fusion gene?
Block in cell differentiation → cells remain immature
76
Targeted therapy for APL?
All-trans retinoic acid (ATRA) and arsenic trioxide
77
Mechanism of ATRA in APL?
Induces differentiation of leukemic promyelocytes
78
Current survival rate in APL with targeted therapy?
~95%
79
What is a major downside of high-dose chemotherapy?
Late-onset complications
80
What is the effect of late chemotherapy complications?
Increased long-term mortality
81
Endocrine late complications of chemotherapy?
Thyroid dysfunction, hormonal imbalance, infertility
82
Cardiac late complications of chemotherapy?
Cardiomyopathy and heart failure
83
Approximate percentage of survivors developing cardiac complications?
Up to 40%
84
What increases the risk of second cancers after leukemia treatment?
High-dose chemotherapy and radiation
85
Prognosis of secondary malignancies after leukemia treatment?
Worse prognosis
86
Major therapeutic innovation in the last 15 years in oncology?
Immunotherapy
87
Main goal of immunotherapy?
Stimulate the immune system to recognize and destroy malignant cells
88
What do immune checkpoint inhibitors do?
Remove inhibitory brakes on T cells
89
Main types of monoclonal antibodies in cancer therapy?
Naked antibodies, conjugated antibodies, and BiTEs
90
What do naked monoclonal antibodies do?
Directly target tumor antigens
91
What do conjugated monoclonal antibodies do?
Deliver toxic drugs or radiation to cancer cells
92
What are BiTEs?
Bispecific T-cell engagers
93
How do BiTEs work?
Bind CD3 on T cells and a tumor antigen (e.g., CD19) on cancer cells
94
What is formed between T cell and tumor cell during BiTE therapy?
Immunological synapse
95
Major limitation of BiTE therapy?
Depends on functional T cells
96
When is BiTE therapy less effective?
In patients with low T-cell count (e.g., after prolonged chemotherapy)
97
What is adoptive T-cell transfer?
Therapy in which T cells are removed, modified, and reinfused into the patient
98
Two sources of T cells for adoptive therapy?
Autologous (patient) or allogeneic (donor)
99
Main steps of adoptive T-cell therapy?
Remove T cells → Modify them → Reinfuse → Destroy malignant cells
100
Two main strategies of T-cell engineering?
TCR engineering and CAR engineering
101
What happens in TCR engineering?
T cells express a new T-cell receptor recognizing intracellular antigens via MHC
102
Limitation of TCR-engineered T cells?
Requires antigen presentation via MHC
103
What happens in CAR engineering?
T cells express a chimeric antigen receptor (CAR) on their surface
104
What does the extracellular domain of CAR derive from?
Antibody fragment that binds tumor antigen
105
What does the intracellular domain of CAR contain?
Costimulatory domains (e.g., CD28, 4-1BB)
106
Function of costimulatory domains in CAR-T cells?
Enhance T-cell activation, proliferation, and persistence
107
Key advantage of CAR-T over TCR therapy?
Recognizes antigens directly on tumor surface (MHC-independent)
108
What happens after CAR-T cells are reinfused?
They proliferate and persist in the patient
109
What do CAR-T cells produce after activation?
Cytokines that amplify immune response
110
Why can CAR-T cells reach difficult sites?
They migrate to tissues including CNS, liver, and soft tissues
111
Why are CAR-T highly effective in liquid cancers?
Tumor cells circulate and are easily accessible
112
Why are CAR-T less effective in solid tumors?
Physical barriers and immunosuppressive tumor microenvironment
113
Example of target antigen in B-cell leukemia for CAR-T?
CD19
114
Why are CAR-T therapies less effective in solid tumors?
Poor penetration into large tumor masses
115
What limits CAR-T access to solid tumors?
Limited vascular access
116
What type of tumor microenvironment reduces CAR-T activity?
Immunosuppressive tumor microenvironment
117
What is “on-target, off-tumor” toxicity in CAR-T therapy?
CAR-T cells attack normal cells expressing the same target antigen
118
Example of on-target, off-tumor effect in CD19 CAR-T therapy?
Destruction of normal B cells
119
Main consequence of B-cell depletion after CD19 CAR-T therapy?
B-cell aplasia
120
Long-term effect of B-cell aplasia?
Immunodeficiency
121
How is immunodeficiency managed after CAR-T?
Regular immunoglobulin (Ig) infusions
122
What is Cytokine Release Syndrome (CRS)?
Systemic inflammatory response after CAR-T activation
123
When does CRS occur?
After CAR-T reinfusion when T cells become activated
124
What causes CRS?
Massive cytokine release
125
Main clinical features of CRS?
High fever, hypotension, respiratory failure, cardiac dysfunction, multi-organ failure
126
Treatment of CRS?
Anti-inflammatory drugs (e.g., IL-6 inhibitors) ± corticosteroids
127
What is ICANS?
Immune Effector Cell–Associated Neurotoxicity Syndrome
128
What causes ICANS?
Inflammation in the CNS
129
Symptoms of ICANS?
Confusion, seizures, brain edema
130
Is CAR-T neurotoxicity usually permanent?
No, generally reversible with prompt treatment
131
Main treatment for ICANS?
Corticosteroids
132
What is stem cell transplantation used for besides leukemia?
Inborn errors of immunity, RBC disorders, metabolic disorders
133
Examples of RBC disorders treated with stem cell transplant?
Thalassemia and sickle cell anemia
134
What is the ideal donor for stem cell transplantation?
HLA-matched sibling donor
135
Probability of finding an HLA-matched sibling?
~25%
136
Alternative to sibling donor?
Unrelated donor (registry match)
137
Approximate success rate of unrelated donor match in Caucasian populations?
~40%
138
What is a haploidentical donor?
Partially matched donor, usually a parent
139
Why is strong immunosuppression needed in transplantation?
To prevent rejection
140
When is stem cell transplantation most effective?
When the patient is in remission
141
Why is transplantation more effective in remission?
The disease burden is minimal
142
First phase of stem cell transplantation?
Bone marrow conditioning
143
Purpose of bone marrow conditioning?
Create space for donor cells
144
How is bone marrow conditioning performed?
High-dose chemotherapy ± radiation
145
Second phase of transplantation?
Infusion of donor stem cells
146
Third phase after transplant?
Donor immune system attacks remaining leukemia cells
147
What is the graft-versus-leukemia (GVL) effect?
Donor immune cells destroy residual leukemia cells
148
Why is GVL beneficial?
It reduces relapse risk
149
What is graft-versus-host disease (GVHD)?
Donor immune cells attack recipient’s healthy tissues
150
Main organs affected in GVHD?
Skin and liver (also GI tract)
151
Key difference between GVL and GVHD?
GVL targets leukemia cells; GVHD targets healthy tissues
152
Why is it important to balance GVL and GVHD?
Need anti-leukemia effect without severe tissue damage
Leukaemia
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