Pediatric Oncology: MDS
Terms
undefined, object
copy deck
- clonal abnormalities associated with MDS
-
monosomy 7 - most common, no prognostic significance in MDS
trisomy 8 and 21
deletion 5q - chromosomal abnormality more commonly seen in treatment-induced AML over de novo AML
- trisomy 8
- what is the prognosis of monosomy 7 in AML compared to MDS
- no prognostic significance in MDS, but poorer prognosis in AML
- what is alkylating agent induced MDS characterized by?
-
deletions or the loss of a whole chromosome
*latency period 3-5 years* - what is epipodophyllotoxin agent induced MDS characterized by?
- translocations involving chromosome band 11q23. Latency period 1-3 years
- what constitutional conditions are associated with JMML
-
NF1
Noonan syndrome
Trisomy 8 mosaicism - what is the renal insufficiency in ALPS due to
- glomerulonephritis attributed to immune deposition of antigen-antibody complexes
- what are IL-10 levels in ALPS?
-
elevated
correlate with disease expression - which types of adult MDS have a high incidence of progression of AML?
-
refractory cytopenia with multilineage dysplasia
refractory anemia with exccess blasts - which types of adult MDS have a low incidence of progression to AML
-
refractory anemia
refractory anemia with ringed sideroblasts
del 5q: macrocytic anemia - which syndromes have an association with MDS
- down, kostman, schwachman diamond, dyskeratosis congenita, blooms, noonans
- definition refractory cytopenia
-
< 2% PB blasts
< 5% marrow blasts - refractory anemia with excess blasts
-
2-19% PB blasts
5-19% marrow blasts - most frequent translocation in MDS -> AML
- AML1/RUNX1
- common marrow finding in M7 AML
- fibrosis
- are GATA-1 mutations seen in TMD or AML
- AML
- platelet markers
- CD 41/42B/61
- clinical features of JMML
-
HSM
LAD
pallor
fever
RASH (can be urticarial) - what is the minimum lab criteria for JMML
-
no t 9:22
PB monocytosis > 1 x 10 to the 9th/L
BM blasts < 20% - what are additional lab criteria of JMML
-
need two of the following:
- hgb F increased for age
- myeloid precursors in PB
- clonal abnormality: monosomy 7, t 5;8, trisony 8, monosomy 22
- GM-CSF hypersensitivity of monocyte progenitors in vitro
- autonomouis growth of CD 34 cells - what is the central pathogenesis of JMML
- RAS activation
- molecular pathogenesis of JMML in Noonan
- missense mutation in PTPN11
- molecular mutations in JMML
-
frequent deletions of NF1 (negative regulator of Ras activation)
missense mutation in PTPN11
mutations of KRAS2 and NRAS - % normal cytogenetics in JMML
- 78
- % tranformation to leukemia in JMML
- 13
- criteria for esstential thrombocytosis
-
platelet count > 600,000
hgb not > 13
normal iron stores
no ph chromosome
no fibrosis of marrow - how common is familial thrombycytosis in pediatric cases of essential thrombocytosis
- 50%
- what platelet morphology is seen in essential thrombocytopenia
-
hyperlobulated
dysplastic
increased early megas - does familial thrombocytosis have malignant transformation?
- no
- incidence of what type of disease in family is associated with LCH
-
thyroid
autoimmune - what cell type is involved in LCH
- dendritic cells
- how do you diagnose LCH
-
intracellular birbeck granules that stain with CD207
OR
extracellular staining with CD1a - what type of nuclei are seen with LCH
- kidney bean, large cytoplasm
- chemo tx for HLH
- vp-16, dex, cyclosporine
- immunohistochemistry of rosai dorfman
-
+ S100
+ CD 163
no CD 1a (differentiate from LCH) - what is the MOST common genetic defect in severe hemophilia
- inversion 42%
- what is the most common genetic defect in mild-moderate hemophilia?
- missense 85%
- how early can you pre-natally detect Factor 8 deficiency
-
11-15 weeks by RFLP chorionic villi/amnio
at 18 weeks can check fetal cord blood for F8 levels - in what situations are clinical manifestations of hemophilia seen in women
-
lyonization of normal x
turner syndrome xo
father with hemophilia/mother carrier
vWD type 2N (normandy) - how can you differentiate a hip bleed from ileopsoas based on physical exam in hemophilia
-
hip -everted
ileopsoas - inverted -
1/2 life factor 8 replacement
factor 9 -
factor 8 - 12 hours
factor 9 - 20-24 hours -
factor dosing replacement
factor 8
factor 9 -
factor 8 50 U/kg for 100%
factor 9 100U/kg for 100% x 1.3 - joint bleeding replacement plan
-
day 1 80% correction
day 2 40% correction
day 3 40% correction - how does DDAVP work in hemophilia
-
activation of contact pathway
plasminogen activiation via TPA
release of VWF from endothelial cells
increased platelet adhesion - side effects from DDAVP
-
hyponatremia
thrombosis
tachyphylaxis - IV dose of DDAVP
- 0.3 microgram/kg in 30 cc NS over 15 min
- dose DDAVP IN
-
< 50 kg: 150 microgram (1 spray)
>50 kg: 300 microgram (2 sprays) - dose amicar
- 100mg/kg q 6hr po for 3-7 days
- what subclass are F8 inhibitors?
-
IGG4
does not fix complement - what is a normal F8 inhibitor level
- < 0.6 bethesda unit
- what does one Bethesda unit equal
- amount of inhibitor that inactivates half of the F8 in the incubation unit
- what is the residual amount of F8 in the presence of 2 bethesda units inhibitor
- 25%
- which molecular abnormalities are associated with inhibitor development
-
large deletions (65-85% risk)
nonsense mutations (stop codon)
inversion of intron 22 (21% risk) - what is the incidence of inhibitor development in factor 9 def compared to factor 8
- much less
- what are the treatment options in hemophilia in the face of inhibitors
-
activated prothrombin concentrates
recombinent factor 7a
porcine factor 8
immune tolerance - dose of activated prothrombin concentrates when treating in presence of inhibitor
- 75U/kg
- how does recombinent F7a work?
- activates factor 9 and factor 10: generate thrombin
- dose of porcine Factor 8
- 50-100U/kg
- Under what clinical scenerio can you expect the best response to porcine Factor 8
-
porcine BU < 15
human BU < 50 - side effects of porcine factor 8
-
allergic reaction
thrombocytopenia
porcine antibody - what determines successful treatment with immune tolerance in hemophilia
-
BU <0.6
recovery > 66%
half life > 6 hours - immune tolerance treatment strategy in hemophilia
-
100U/kg/d rF8 until BU< 0.6, recovery >66%, t 1/2 > 6 hours then 100U/kg/d x one month
50U/kg/d x 1 mos
50U/kg/qod x 1 mos
then 20-30 U/kg/tiw x 12 months (this is the prophylactic dose) - what is the definition of a target joint
-
4 bleeds/joint over 6 months
20 bleeds/joint in a lifetime - where is von willebrand factor stored
- endothelial cells and platelets
- how does ristocetin induce platelet agglutination?
- vWF interaction with platelet receptor Ib/IX
- what is the relationship between vWF levels and blood type
- lower levels are seen with type O, highest with AB
- tests in type 1 vWF
- proportionally reduced F8, ristocetin cofactor, and vWF antigen
- what is the defect in vWF
- functionally and structually normal just less of it
- what is the defect in VWF type 2A
- absence of large and intermediate sized vWF multimers
- what is the defect in vWF type 2B
- increased vWF affinity for platelet GP1b and secondary clearance of large sized multimers
- platelet count in vWF type 2B
- thrombocytopenia
- treatment contraindication in vWF type 2B
- DDAVP