270. ALL

Question 1

Acute Lymphoblastic Leukemia

• Definition, ALL vs LBL
• epi: demo, age, sex, subtypes
• RFs (3)

Answer 1

ALL/LBL: aggressive neoplasms of precursor lymphoid cells (lymphoblasts)
ALL: leukemia (neoplastic lymphoblasts in blood and BM)
LBL: lymphoma (blasts mainly infiltrate extramedullary tissue - LN, spleen, thymus)

Epi: Primarily disease of CHILDREN (75% <6yo), second peak in adults >60yo

• MOST COMMON CANCER OF CHILDREN
• Boys > Girls
• 85% of ALL are B-ALL (more bone marrow B cell precursors present early in life)
• 15% of ALL are T-ALL (T-ALL are 90% of LBL - occurs more frequently in ADOLESCENCE when thymus reaches max size

Eti: 1. Ionizing radiation, 2. Familial (inherited TP53 mutation), 3. Down Syndrome

Question 2

ALL

• pathophys
• CP of B-ALL vs T-ALL

Answer 2

PPhys: genetic alterations causing mutation arrest at blast stage and driving proliferation = bone marrow replaced by neoplastic blasts = cytopenias

B-ALL: ABRUPT onset (days to weeks), sx of anemia, thrombocytopenia, neutropenia, WBC count may be low/normal/high, B sx (fever, night sweats), Hepatosplenomegaly, Testicular enlargement, Bone PAIN, CNS involvement (neuro sx)

T-ALL: large anterior mediastinal mass = SVC syndrome (pain, dysphagia, dyspnea, swelling of neck/face/upper limbs due to SVC obstruction), CNS involvement

Question 3

ALL

• morphology on CBC
• IHC of all ALL vs. B-ALL vs T-ALL

Answer 3

CBC: lymphoblasts (small to medium size), HIGH N:C ratio, dispersed-to-slightly condensed nuclear chromatin, NO AUER RODS (AML), +”HAND MIRROR CELLS” - asymmetric cytoplasmic projection

IHC

• Immaturity: TdT
• B lymphoblasts: CD19
• T lymphoblasts: CD3, CD1a

Question 4

B-ALL Genetics: 2 low risk and 4 high risk

Answer 4

LOW RISK

1. Hyperdiploidy (>50 chromosomes) = favorable outcome
2. t(12;21) ETV6-RUNX1 = more common in children = favorable prognosis

HIGH RISK

1. t(9;22) = BCR-ABL Ph Ch = more common in adult with B-ALL = unfavorable prognosis = targeted tx with imatinib greatly improves outcome
2. Ph-like = similar gene expression profile to Ph Ch without t(9;22) = poor prognosis
3. t(v;11q23.3) = KMT2A rearrangement = most common leukemia in infants = high WBC, organomegaly, CNS involvement = Poor prognosis
4. Hypodiploidy (<46 Ch) = poor prognosis

Question 5

ALL

• prognostic factors (4) - which is most important?
• tx

Answer 5

Prognosis

1. Age (favorable age 2-10; unfavorable <1 or >60)
2. Cytogenetics (favorable t(12;21), hyperdiploidy; unfavorable KMT2A, t(9;22), Ph-like, low hypodiploidy)
3. Time to response to induction chemotx (Favorable rapid response) [MOST IMPORTANT]
4. CNS/Testicular involvement at initial dx (ADVERSE)

Tx:
1. Induction Chemotx (4w): complete remission (eradicate all leukemia from bone marrow)
2. Consolidation Chemotx (4-8m): ongoing tx to prevent regrowth, reduce tumor burden, prevent emergence of drug resistance in leukemic cells
3. Maintenance Chemotx (2-3y): less intense than consolidation to prevent relapse
CNS Prophylaxis: prevent CNS relapse, begins at induction phase and continues throughout