Oncology

Question 1

ALL

Definition

Answer 1

Too many lymphoblasts (immature WBCs) in the blood & Bone marrow

Question 2

ACGS BPG age cut off for paediatric ALL

Answer 2

25 years old

Question 3

ALL Reporting Time Guidelines

New diagnosis

Routine

Answer 3

New Diagnosis: 95% within 14 calendar days

Routine: 95% within 21 calendar days

Question 4

What are the clinical features of ALL?

Answer 4

• Fever, fatigue, bone/joint pain, shortness of breathe, weight loss, bruising, infection, lymphadenopathy/splenomegaly, anaemia, neutropenia, thrombocytopenia.

Question 5

What are the Common Genetic abnormalities in adult ALL?

Answer 5

1. t(9;22)(q34;q11) BCR-ABL1 Ph chr.
   - POOR PROG (9% 5 yr survival).
   - Most common rearrangement in adult ALL (25-30%).
   - Secondary abnorm: +Ph, -7/7q-, del(9p), +8,+X, and HeH (high hyper diploids)!
2. t(4;11)(q21;q23) KMT2A (MLL) - AFF1
   - POOR PROG (33% 3 yr survival
   - KMT2A found about 10% adult ALL, t(4;11) most common!
3. Complex Karyotype (5 or more): Poor Prog
4. Ploidy: High Hyperdiploidy (HeH - 51-65 chromosomes)
   - GOOD PROG: 7% adult ALL
   - Commonly Gaines: 4,6,10,14,17,18,21,X
   - usually result in trisomy for gained chromosomes (except 21, tetrasomy), rather than tetrasomy. Important to distinguish from doubling up of near haploid / low hypoid diploid.
5. Hypodiploidy (<44 chromosomes) & near triploidy
   - POOR PROGNOSIS.
   - Commonly retained: 1,4,5,6,8,10,11,18,19,21,22 & sex chromosomes (common loss of 3 & 7).
   - Low hypodiploidy is more common than near haploid (converse true for infants).

Other rearrangements:
TCF3 rearrangement: Adult <5%.
- t(1;19) (TCF3 - PBX1 gene fusion) most common.
- Important to characterise TCF3 by FISH as t(1;19) has intermediate prog & t(17;19) (TCF3 -HLF) has POOR prognosis.

IGH:
- more common in T-ALL
Dic (9;12): PAX5 - ETV6, more common in children but reported in adults. ? Very good prognosis.

Question 6

What are common abnormalities in infant/childhood ALL?

Answer 6

(1) . t(12;21) ETV6-RUNX1
- 25% in childhood, not seen in infants.
- Crytpic - FISH or RT-PCR
- common loss of other functional ETV6.
- Secondary abnorm: CDKN2A, PAX5 & IKZF1 del)
- GOOD PROG (>90% cure rate)!!

(2) . iAMP21 (intrachromosomal amplification of chr 21):
- 2% in paed B-ALL.
- 5 or more copies of RUNX1 (21q22), 3 or more extra copies on one chr21.
- if uncertainty between iAMP21 & high hyperdiploidy use metaphase FISH!
- Childhood prognosis is poor (but improved by intensive treatment protocols).

(3). KMT2A rearrangements:
- most common abnorm in infants =60-80%, 50% are t(4;11)(q21;q23) KMT2A- AFF1, i7q common dev, poor prog
- Childhood = 3-8%
Others: t(9;11) KMT2A- MLLT3
T(11;19)(q23;p13.3) KMT2A- MLLT1

(4) . High hyperdiploidy (51-65 chr):
- 25-30% childhood B-ALL, good Prog
- Commonly Gained: 4,6,10,14,17,18,21,X. Gained chr tens to be trisomies.

(5) . t(9;11), 2-4% childhood, poor prog
- Maj have IKZF1 del.

(6) . Near haploidy (23-29 chr)/low hypodiploidy (30-39)/ high hypodiploidy (40-44):
- Rare finding, poor prognosis.
- near haploidy confines to childhood.

(7) . TCF3 rearrang., 5-6% childhood ALL
- t(1;19) TCF3-PBX1, most common: interned prog
- The rare t(17;19) TCF3-HLF is poor prog, so essential to distinguish between the 2…

Question 7

WHO Classification of ALL

Answer 7

B-lymphoblastic leukaemia/lymphoma

NOS
With recurrent genetic abnormalities:
With t(9;22); BCR-ABL1
With t(v;11) KMT2A rearranged
T(12;21) ETV6-RUNX1
With hyperdiploidy
With hypodiploidy
With t(5;14) IL3-IGH
With t(1;19) TCF3 PAX1
Provisional BCR-ABL1 like
Provisional iamp21

T-lymphoblastic leukaemia/lymphoma
Prov Early T cell precursor
Prov Natural Killer cell