Leukemias

Question 1

Conditions causing high LAP score

Conditions causing low LAP score

Answer 1

Myelofibrosis, leukemoid reactions, PCRV, infections, steroids, Cushings, OCP

CML, pernicious anemia, IMN, PNH

Question 2

Good prognostic factors in ALL

Bad prognostic factors

Immunophenotyping

Answer 2

FAB L1, common ALL, Pre B phenotype, low WCC

FAB L3, T and B cell surface markers, high WCC, male sex, age <2, >10yrs, Ph Chr, non caucasian
B-cell

Question 3

Drug used in CLL treatment most likely to cause TLS

Answer 3

Venetoclax

Question 4

CML features

Answer 4

1/5 cases of adult leukemia
Median age 60-65
Inv -Elevated WCC, enlarged spleen, constitutional symp
Phases -chronic, accelerated, blast crisis

Question 5

Mutation causing resistance to TKI (except imatinib)

Answer 5

T315i

Question 6

Side effects of imatinib

Answer 6

Fluid retention ,muscle aches, cramps
GI -diarrhoea
Common S/E of TKI -rash, electrolyte derangement, marrow suppression, LFT derangement

Question 7

S/E Nilotinib

Answer 7

Pancreatitis
Vascular events
HTN, hyperglycemia
Cardiac conduction

Question 8

S/E Dasatinib

Answer 8

Pleural, pericardial effusion

Bleeding risk

Question 9

S/E ponatinib

Answer 9

Rash ,pancreatitis, vascular events

Question 10

Driver mutations affecting prognosis in MPN

Answer 10

JAK2, CALR, MPL
Triple negative patients -poor prognosis

CALR -more favourable prognosis than JAK-2 and MPL, higher platelet counts, lower thromboembolic
High JAK-2 associated with clinical markers of disease progression in MF

Question 11

Therapy related AML

Answer 11

Topo-11q23, alk - del 5,7

Question 12

Clinical features of AML

Immunophenotyping (flow cytometry)

Answer 12

Pancytopenia, hyperleucocytosis, splenomegaly,chloroma, gum infiltration
Flow - CD13, CD 33 - Myeloid antigens

Question 13

Patient factors that indicate unfit for chemo in AML

Answer 13

Age>75 or between 60-74 with one of following:
ECOG 2-3, CHF, C/C stable angina, EF<50%
DLCO<65%, FEV1<65
Cr Cl 30-45
Bn -1.5-3 ULN

Question 14

Targeted therapy in AML

Answer 14

FLT3 ITD-Midostaurin given with 7+3

Venetoclax +Azacitidine/Low dose Cyt - elderly AML

Question 15

Faetures of differentiation syndrome

Answer 15

Cytokine release syndrome
Occurs with Rx for APML -As+ ATRA
Fever, peripheral edema, pulmonary opacities, hypoxemia, resp distress, hypotension, renal and hepatic dysfunction, rash, serositis -pleural and percardial effusion.
Mx -cease Rx temporarily, give steroids

Question 16

Prognostic features in AML

Answer 16

AGE IS STRONGEST PROGNOSTIC FACTOR
Clinical -age>75, ECOG>1, prior MDS/MPN, t-AML,High WCC
Cytogenetic - Good: Inv 16,t(8:21),t(15;17)
Poor: Inv 3, t(6:9),t(11q23),-5/5q,-7
Molecular: Good:NPM1,CEBPA
Poor: FLT3-ITD,RUNX1,TP53, ASXL1

Question 17

Leukemia presenting with SVC obstruction

Answer 17

T cell ALL

Question 18

Poor risk factors in ALL

Answer 18

Clinical - age >35, preT, pro B, WCC>30, No CR after 4 weeks
Genomic -t(4:11),t(9,11)
Favourable - hyperdiploidy(15-65, trisomy of Ch4,10,17
E2A-PBX1
ETV6-CBFA2

Question 19

Rx for ALL

Answer 19

Classic :Hyper CVAD, CNS Px with IT Mtx
L-asparaginase in younger patients
Ph+ ALL- Imatinib/ dasatinib
Rituximab in B-ALL if CD20+

Question 20

Blinatumomab in ALL

Answer 20

Anti-CD19/CD3- Links B cell and T cell and activates T cell to exert cytotoxic activity on B cell
In relapsed/refractory ALL
Toxicity -Cytokine release syndrome, encephalopathy

Question 21

Mutation with favourable prognosis in MDS

Answer 21

SF3B1 –low risk of transformation to a/c leukemia

Isolated deletion of 5q (without P53)

Question 22

MDS risk stratification basis

Answer 22

R-IPSS MDS Score :BM blasts, cytopenias,karyotype

Question 23

Rx of MDS

Answer 23

High IPSS -Azacytidine
Transfusion dependent -Iron chelation
5q- -Lenalidomide
Hypoplastic MDS - ATG,CsA
Younger patient -allogeneic transplant

Question 24

Marker of poor chemotherapy response in CLL

Answer 24

Biallelic deletion of 17p (TP53 resides on 17p)

No TP53 mediated apoptosis of DNA damaged by chemo