Leukemia

Question 1

Most common childhood cancer (peak age ~4 years)

Answer 1

Acute Lymphoblastic Leukemia

Question 2

Definition of ALL

Answer 2

 Malignancy of lymphoblasts (immature B or T cells)
 Most common childhood cancer (peak age ~4 years)
 May cause marrow suppression (anemia, thrombocytopenia, neutropenia)

Question 3

Clinical Features of ALL

Answer 3

 Bone pain (marrow expansion)
 Fever, fatigue
 Hepatosplenomegaly, lymphadenopathy
 CNS involvement: Headache, vomiting, meningeal spread

Question 4

In diagnosis of ALL
CBC , bone marrow biopsy, flow cytometry will show? Respectively

Answer 4

Anemia, thrombocytopenia, lymphoblasts

Hypercellular marrow with >20% lymphoblasts

o Pre-B cell (most common): CD10 (CALLA), CD19, CD22
o Pre-T cell: CD2, CD3, CD5, CD7
o TdT+ (marker of immature lymphoid cells)

Question 5

TdT+

Answer 5

ALL (marker of immature lymphoid cells)

Question 6

Genetic association with ALL
………… Good prognosis(common in children)
………… Poor prognosis(more common in adults)
………… (10–20× increased risk) for ALL

Answer 6

t(12;21) TEL-AML1

t(9;22) Philadelphia chromosome (BCR-ABL)

Down Syndrome

Question 7

Good prognosis (>85% cure rate in children)

Answer 7

ALL

Question 8

Treatment of ALL

Answer 8

 Induction therapy (Vincristine, steroids, Asparaginase)
 CNS prophylaxis (intrathecal chemotherapy)

Question 9

Most common acute leukemia in adults (median age 65 years)

Answer 9

Acute Myeloid Leukemia (AML)

Question 10

Splenomegaly uncommon

Answer 10

Acute Myeloid Leukemia

Question 11

Clinical Features of AML

Answer 11

Symptoms from marrow failure:
o Anemia → Fatigue, pallor
o Thrombocytopenia → Bleeding (gums, petechiae)
o Neutropenia → Infections
 Splenomegaly uncommon (contrast with ALL)
 LDH often elevated (high cell turnover)

Question 12

How to diagnose AML

Answer 12

 CBC: Anemia, thrombocytopenia, variable WBC
 Bone marrow biopsy: >20% myeloblasts
 Peripheral smear: Auer rods (pathognomonic)
 Myeloperoxidase (MPO) positive (marker of myeloid lineage)

Question 13

Peripheral smear: Auer rods (pathognomonic)

Answer 13

AML

Question 14

Acute Promyelocytic Leukemia (APML)?

Answer 14

Subtype from AML

Question 15

DIC common at presentation

Answer 15

Acute Promyelocytic Leukemia (APML)

Question 16

Translocation: t(15;17) → PML-RARA fusion gene

Answer 16

Acute Promyelocytic Leukemia (APML)

Question 17

How to treat Acute Promyelocytic Leukemia (APML)

Answer 17

All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide

Question 18

How to treat AML

Answer 18

 Induction therapy: Cytarabine + Daunorubicin
 Bone marrow transplant for high-risk cases

Question 19

Most common leukemia in older adults (>60 years)

Answer 19

Chronic Lymphocytic Leukemia (CLL)

Question 20

Clinical Features of CLL

Answer 20

 Often asymptomatic (found on routine CBC)
 Lymphocytosis (>5000/μL)
 Lymphadenopathy, hepatosplenomegaly
 Autoimmune hemolytic anemia (AIHA)
 Recurrent infections (hypogammaglobulinemia)

Question 21

Autoimmune hemolytic anemia (AIHA) may seen in

Answer 21

CLL

Question 22

Smudge cells

Answer 22

CLL

Question 23

Recurrent infections (hypogammaglobulinemia)

Answer 23

CLL

Question 24

CD19+, CD20+, CD5+ (abnormal for B-cells)

Answer 24

CLL

Question 25

Complications of CLL

Answer 25

Richter Transformation: CLL → Diffuse Large B-cell Lymphoma (DLBCL) Autoimmune Hemolytic Anemia (AIHA)  Autoantibodies attack RBCs → Anemia Hypogammaglobulinemia (Low IgG, IgA, IgM)  Increased bacterial infections

Question 26

Treatment of CLL

Answer 26

 If symptomatic: BTK inhibitors (Ibrutinib), Anti-CD20 (Rituximab)  If asymptomatic: Observation Chemotherapy (For High-Risk Cases) o Fludarabine + Cyclophosphamide + Rituximab (FCR regimen)

Question 27

There is a related disorder with CLL (Increased WBCs) called …………… (Normal WBCs but enlarged lymph nodes)

Answer 27

Small Lymphocytic Lymphoma (SLL)

Question 28

Associated with Philadelphia Chromosome (t(9;22), BCR-ABL)

Answer 28

CML

Question 29

Chronic Phase of CML

Answer 29

Often asymptomatic, detected on routine CBC  Mild fatigue, weight loss, splenomegaly  Peripheral blood findings: o Leukocytosis (~100,000 WBC/microL) o ↑ Neutrophils, basophils (hallmark), eosinophils o ↑ Myelocytes (myelocyte bulge) o Mild anemia, normal/increased platelets

Question 30

Basophilia on smear

Answer 30

(CML hallmark)

Question 31

May progress to blast crisis (resembles acute leukemia)

Answer 31

CML

Question 32

Diagnosis of CML

Answer 32

 CBC: Leukocytosis with left shift (immature granulocytes)  Bone marrow biopsy: Hypercellular with granulocyte expansion  PCR for BCR-ABL fusion gene (confirmatory test)

Question 33

PCR for BCR-ABL fusion gene (confirmatory test)

Answer 33

CML

Question 34

Uncontrolled proliferation of granulocytes (neutrophils, basophils, eosinophils)

Answer 34

Chronic Myeloid Leukemia (CML)

Question 35

Peripheral blood findings: o Leukocytosis (~100,000 WBC/microL) o ↑ Neutrophils, basophils (hallmark), eosinophils o ↑ Myelocytes (myelocyte bulge) o Mild anemia, normal/increased platelets

Answer 35

CML

Question 36

Accelerated Phase of CML

Answer 36

 Worsening symptoms, increasing WBC despite treatment  More myeloblasts in blood and marrow

Question 37

What is Blast Crisis ?

Answer 37

 >20% blasts in blood or bone marrow  Usually transforms into Acute Myeloid Leukemia (AML), rarely ALL  Severe symptoms: fever, bone pain, worsening cytopenias

Question 38

Rare chronic B-cell leukemia . Associated with BRAF mutation (~100%)

Answer 38

Hairy Cell Leukemia

Question 39

"Dry tap" on bone marrow aspiration

Answer 39

Bone marrow transplant (only if TKI-resistant) Hairy Cell Leukemia

Question 40

Treatment of Hairy Cell Leukemia

Answer 40

Purine analogs (Cladribine, Pentostatin)

Question 42

Bone marrow biopsy: Fibrosis (dry tap

Answer 42

Hairy cell leukaemia

Question 43

Clinical features of Hairy cell leukaemia

Answer 43

Massive splenomegaly (abdominal pain)  Pancytopenia (caused by marrow fibrosis)  "Dry tap" on bone marrow aspiration  Recurrent infections (low neutrophils)