Leukemias Flashcards
Conditions causing high LAP score
Conditions causing low LAP score
Myelofibrosis, leukemoid reactions, PCRV, infections, steroids, Cushings, OCP
CML, pernicious anemia, IMN, PNH
Good prognostic factors in ALL
Bad prognostic factors
Immunophenotyping
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
Drug used in CLL treatment most likely to cause TLS
Venetoclax
CML features
1/5 cases of adult leukemia
Median age 60-65
Inv -Elevated WCC, enlarged spleen, constitutional symp
Phases -chronic, accelerated, blast crisis
Mutation causing resistance to TKI (except imatinib)
T315i
Side effects of imatinib
Fluid retention ,muscle aches, cramps
GI -diarrhoea
Common S/E of TKI -rash, electrolyte derangement, marrow suppression, LFT derangement
S/E Nilotinib
Pancreatitis
Vascular events
HTN, hyperglycemia
Cardiac conduction
S/E Dasatinib
Pleural, pericardial effusion
Bleeding risk
S/E ponatinib
Rash ,pancreatitis, vascular events
Driver mutations affecting prognosis in MPN
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
Therapy related AML
Topo-11q23, alk - del 5,7
Clinical features of AML
Immunophenotyping (flow cytometry)
Pancytopenia, hyperleucocytosis, splenomegaly,chloroma, gum infiltration
Flow - CD13, CD 33 - Myeloid antigens
Patient factors that indicate unfit for chemo in AML
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
Targeted therapy in AML
FLT3 ITD-Midostaurin given with 7+3
Venetoclax +Azacitidine/Low dose Cyt - elderly AML
Faetures of differentiation syndrome
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
Prognostic features in AML
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
Leukemia presenting with SVC obstruction
T cell ALL
Poor risk factors in ALL
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
Rx for ALL
Classic :Hyper CVAD, CNS Px with IT Mtx
L-asparaginase in younger patients
Ph+ ALL- Imatinib/ dasatinib
Rituximab in B-ALL if CD20+
Blinatumomab in ALL
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
Mutation with favourable prognosis in MDS
SF3B1 –low risk of transformation to a/c leukemia
Isolated deletion of 5q (without P53)
MDS risk stratification basis
R-IPSS MDS Score :BM blasts, cytopenias,karyotype
Rx of MDS
High IPSS -Azacytidine Transfusion dependent -Iron chelation 5q- -Lenalidomide Hypoplastic MDS - ATG,CsA Younger patient -allogeneic transplant
Marker of poor chemotherapy response in CLL
Biallelic deletion of 17p (TP53 resides on 17p)
No TP53 mediated apoptosis of DNA damaged by chemo
