B-ALL

Question 1

B-ALL Morphologically and IMPT defined

Answer 1

>20% Blasts

Pro-B: CD19, CD22, CD79a and TdT
Common-B: CD10
Pre-B: cIgM
Transitional-B: HC but not LC

Question 2

Features of B-ALL with high hyperdiploidy

Answer 2

• 51-56 chromosomes
• Kids
• Mutation in RTK-Ras pathway
• Good Prognosis

Question 3

Features of B-ALL with hypodiploidy

Answer 3

• < 43 chromosomes
• Teens and adults
• TP53 mutations
• Poor Prognosis

Question 4

Modalities for detection of aneuploidy

Answer 4

I. Karyotype
* Metaphase
* 20 cells cultured
* 2 cells for abN and 3 cells for loss of chromosome

II. FISH
* Interphase

III. Flow
* DNA Index (DI)
* Ratio of MFI Blasts : Normal cells
* < 0.9 Hypodiploidy and > 1.16 Hyperdipoidy

Question 6

Features of B-ALL with BCR::ABL1

Answer 6

• t(9;22) p190
• Increases with age
• Myeloid Markers CD13, CD33 (and CD25)
• Poor prognosis

Question 7

Features of B-ALL with KMT2A

Answer 7

• 11q23 (+++ fusion partners)
• Infants
• > WCC and CNS involvement
• Positive for CD19, Negative for CD10, TdT and CD24
• Myeloid markers CD15 and CD65
• Poor prognosis

Question 8

Features of B-ALL with TCF::PBX1

Answer 8

• t(1;19)
• Kids
• Pre-B: CD19, CD10 and cIgM
• Bright CD9 and Dim to negative CD34
• Intermediate risk

Question 9

Features of B-ALL with TCF3::HLF

Answer 9

• t(19;17)
• Rare
• Kids
• Poor prognosis

Question 10

Features of B-ALL with IgH::IL3

Answer 10

• t(5;14)
• Kids and teens
• Eosinophils with low/no PB blasts
• Common-B: CD19 and CD10
• Myeloid markers CD13, CD33 and CD123

Question 11

Features of B-ALL with ETV6::RUNX1

Answer 11

• t(12;21)
• kids
• Positive CD9, CD20, CD66c and CD17
• Myeloid Markers CD13 and CD33
• Good prognosis

Question 12

Features of B-ALL with iAMP21

Answer 12

• Kids
• Low WCC
• Poor prognosis (High relapse rate)

Question 13

Features of B-ALL with BCR::ABL1-like

Answer 13

• Mutations consituitively activate JAK/STAT
• > with age and DS
• High WCC
• Poor prognosis

Question 14

Features of B-ALL with ETV6::RUNX1-like

Answer 14

• Kids
• CD27 Positivity

Question 15

DDx for B-ALL with Myeloid Markers

Answer 15

1. BCR::ABL1 (CD13,CD33 and CD25)
2. KMT2A (CD15 and CD65)
3. IgH::IL3/t(5;14) (CD13, CD33 and CD123)
4. ETV6::RUNX1/t(12;21) (CD13, CD33)

Question 16

Predictors of adverse prognosis in B-ALL (6)

Answer 16

1. Age < 1 & > 10 (Africans and Boys)
2. WCC > 50
3. Slow blast clearence
4. Genomic entities (Hypodiploidy)
5. MRD post-induction and consolidation (Nr 1 predictivie factor - MRD Neg = < 0.01%)
6. CNS involvement

Question 17

Treatment options for B-ALL

Answer 17

Chemo±Immunotherapy:
I. Chemo:
* BFM (Berlin, Frankfurt and Munster) protocol
* HyperCVAD (Cyclophos, Vincristine, Doxorubicin, Dexa

II. Immuno:
* Mabs (Ritux)
* TKI (for BCR::ABL1)
* ADCs (Inotuzumab)
* T-cell engagers (Blinatumumab)
* CART (CD19 and CD22)