Acute Lymphoblastic Leukemia

Question 1

Genetic disorders that predispose to ALL

Answer 1

Down syndrome
NF-1
Li fraumeni
Bloom syndrome
Ataxia telangiectasia
Nijmegen breakage syndrome 
Constitutional mismatch repair syndrome 
Noonan syndrome

Question 2

Flow cytometry features of pre B ALL

Answer 2

TDT+ cd34 + CD45 dim, CD19+, CD22+, CD79a*, cIg

Often CD10+

Question 3

Recurrent Cytogenetic abnormalities in ALL and significance

Answer 3

T( 9;22)- BCR-ABL- Philadelphia positive ALL- harder to treat
T(12;21) ETV6-RUNX1- favourable
Double trisomy 4, 10- favourable
T(1;19)-TCF-PBX1- higher incidence of CNS disease- not prognostic on its own
KMT2A rearranged- infant ALL, poor prognosis CD10-
IAMP21- poor prognosis

Question 4

Definition of hyperdiploid and hypodiploid ALL

Answer 4

Hyperdiploid > 47 chromosomes
Hypodiploid <44

Low hypodiploid- <32

Question 5

Describe the pathways involved in Philadelphia like ALL and associated cytogenetics/ molecular features

Answer 5

ABL- pathways
ABL1/2
PDGFRB
CSFR1

JAK-STAT pathways
CRLF2
EPOR fusion/JAK 1/2

Many ph like have IZKF1 rearrangements but not driver mutation

Question 6

Prognostic factors in ALL

Answer 6

Response to therapy- MRD EOI B cell ALL and MRD EOC for T cell all
WBC > 50,000 at diagnosis
Age < 1 or >10
Cytogenetics favourable or not
CNS or extramedullary disease

Question 7

Describe CNS disease staging in ALL

Answer 7

CNS 1- WBC < 5 and no blasts
CNS 2a- WBC < 5 with blasts, no red cells
CNS 2b- WBC <5 with blasts and blood Traumatic tap but negative by steinhertz bleyer algorithm
CNS 3a- WBC > 5 and blasts
CNS 3b- traumatic tap, positive by algorithm
CNS 3 c- frank CNS disease

Question 8

What is the steinhertz bleyer algorithm for a traumatic tap

Answer 8

considered CNS disease ( 3b) if the ratio of the CSF WBC/RBC > 2X the peripheral blood WBC/RBC ratio

Question 9

Features of cytokines release syndrome

Answer 9

Fever
Hypotension
Respiratory distress
Renal dysfunction 
Coagulopathy
Encephalopathy

Question 10

What is ICANS stand for and what are symptoms?

Answer 10

Immune effector therapy induced neurological dysfunction ( used to be called CRES- cytokines release encephalopathy syndrome)

Symptoms
Dysarthria language distribution
Confusion
Dysgraphia
Tremors

Question 11

Describe the standard treatment for B cell All- average risk

Answer 11

3 drug induction- asparaginase, vincristine, dex

Consolidation- IV methotrexate, VCR and 6 MP
IM I- capizzi methotrexate
Delayed intensification- dexamethasone, vincristine, asparaginase, daunorubicin, arac, cyclophosphamide)
IM II- capizzi methotrexate
Maintenance q12 week pulses vincristine, pred and 6MP/ methotrexate

Question 12

Describe the standard therapy for HR B cell ALL

Answer 12

4 drug induction - VCR, doxo, asparaginase, pred 30 d > 10, dex 14 < 10
Consolidation- vincristine, asparaginase, cyclophosphamide, 6- MP, cytarabine,
IM1 - HD methotrexate
DI- vincristine, dauno, asparaginase, 6 TG, dexamethasone, cyclo, ara-6
IM II- capizzi methotrexate
Maintenance q 1 month vincristine, steroid pulse and 6 MP/methotrexate

Question 13

Immuno phenotype of early T cell precursor ALL?

Answer 13

Cd1a negative, CD8 negative CD5 weak

Often expresses myeloid antigens