Acute lymphoblastic leukemia

Question 1

Which chemotherapy agent has shown activity against relapsed or refractory T-ALL as a single agent?

Answer 1

Nelarabine

Question 2

What is the proper radiation regimen in CNS3 T ALL?

Answer 2

18Gy to whole brain, including posterior halves of eyes

Question 3

What are the specific translocations in Burkitt (3)?

Answer 3

C-myc
t(2;8)
t(8;14)
t(8;22)

Question 4

Define CNS3 status?

Answer 4

Presence of 5 of more WBC and cytospin positive for blasts

Question 5

Name prognostic factors in infant ALL (5)

Answer 5

1. Age
2. WBC at diagnosis
3. MLL rearrangement
4. Response to therapy
5. MRD

Question 6

Name 5 predisposition syndrome for ALL

Answer 6

1. Li-Fraumeni
2. PAX5
3. NF1
4. Bloom syndrome
5. Ataxia-telangiectasia

Question 7

What cytogenetic anomaly is associated with hypereosinophilia at diagnosis of ALL?

Answer 7

t(5;14)(q31;q32

Question 8

Who is more at risk of developing osteonecrosis?

Answer 8

Teenagers, females, patients on treatment

Question 9

What is the most important prognostic factor in ALL?

Answer 9

MRD

Question 10

Name 3 good cytogenetic features

Answer 10

1. Hyperdiploidy
2. ETV6-RUNX1
3. Trisomies 4, 10, 17

Question 11

What is the mechanism of allopurinol and rasburicase?

Answer 11

Allopurinol: competitive inhibition of xanthine oxidase, leading to decreased formation of uric acide
Rasburicase: recombinant urate oxidase, which promotes catabolism of uric acid into allantoin (water soluble, easily excreted in urine)

Question 12

Which patients required CNS radiation?

Answer 12

CNS3
T-cell ALL
Patients presenting with very high WBC count at Dx (?)

Question 13

What is the prognosis of infant ALL?

Answer 13

EFS: 20-40%

Question 14

How is defined hematologic remission following induction for ALL?

Answer 14

Normocellular bone marrow with blasts < 5% and absence of blasts in peripheral blood;
Should be done in context of almost normal counts, i.e. ANC > 500 and platelets > 100 000

Question 15

Primary induction failure in ALL

• Incidence
• RF
• Prognosis

Answer 15

<5% of cases
RF: T-cell ALL, high WBC at presentation
Poor prognosis (OS: 30%); might be improved by HSCT in first remission

Question 16

In maintenance therapy for ALL, why do we use 6MP rather than 6TG?

Answer 16

Higher rates of hepatotoxicity (VOD, cirrhosis) are seen with 6-TG
6-TG has theoretical advantage of not relying on TPMT for metabolism and is potent in vitro, but no clinical benefit proven (efficacy seems equivalent between both)

Question 17

Discuss pros and cons of prednisone and dexamethasone in ALL treatment

Answer 17

Dexamethasone is more potent than prednisone, has more CNS penetration and is associated with better EFS.
However, associated with more toxicities, especially in older children and adolescents, including osteonecrosis, fractures, infections.

Question 18

Recommended supportive therapies in infant ALL (8 measures)

Answer 18

IV broad spectrum Atbx for F&N
Empiric antifungal therapy for persistent fever * 3-5 days
Consideration of antifungal prophylaxis
PJP prophylaxis
RSV Prophylaxis
Influenza vaccination
IVIg replacement 
Prolonged hospitalisation until marrow recovery

Question 19

Prognostic factors in infant ALL

Answer 19

• Age
• WBC at presentation
• MLL rearrangement
• Response to prednisone (number of blasts at D8)
• MRD