Heme Onc Board Prep Flashcards
Cytogenetics: t(8:21)
Molecular:
FAB:
Characteristics:
Cytogenetics: t (8:21)
Molecular: RUNX1
FAB: M2
Characteristics: Auer Roads, Chloromas, CNS+, good prognosis
Cytogenetics: inv 16
Molecular:
FAB:
Characteristics:
Cytogenetics: inv 16
Molecular: CBFB-MYH11
FAB: M4Eo
Characteristics: Eos with baso granules, chloromas, CNS+, good px
Cytogenetics: t (15;17)
Molecular:
FAB:
Characteristics:
Cytogenetics: t(15;17)
Molecular: PML-RARA (APL)
FAB: M3
Characteristics: Granules/Auer rods, DIC/bleeding, good px with ATRA
Cytogenetics: 11q23
Molecular:
FAB:
Characteristics:
Cytogenetics:11q23
Molecular: MLL(KMT2A)
FAB: M4/m5
Characteristics: infant, WBC/skin/CNS/gums, t-AML after topo II inhibitor
therapy related AML:
Topo II inhibitors, etop, anthracyclines, platinums
-Genetics?
- Treatment?
1-2 year onset
presents in fulminant AML
11q23 common but can be seen in 8;21, 15;17, 9;22, inv16
treat with chemo and HSCT
treatment related AML: alkylators and radiation
-genetics?
- Treatment?
5-7 onset
MDS precedes AML
-5, del5q, del 7q
Chemo and HSCT
leukemia rates in mono twins
increased risk, younger the first twin is at dx, the higher the risk of second twin (<1 year old). over 6 is minimal. between 1-6 is 20%
AML Favorable Characteristics:
(5)
- DS <4 yo
- APL t(15;17)
- inv 16, 8;21
- Molecular: NPM1, CEBPA
- MRD neg after course 1
Unfavorable characteristics of AML
(5)
- t-AML, MDS-AML
- monosomy -7, 5q, 3q
- FLT3/ITD molecular
- induction failure (>5% blasts after course 2)
- MRD positive after course 1
AML Induction regimen
Dauno, cytarabine, gemtuz +/- etop
CML originates from abnormal pluripotent HSC. it is PH+, 9;22 BCRABLE +. What are the 3 phases
Chronic: <10% in marrow and blood
Accelerated; 10-19%
Crisis: >20%
P210 is asstd with…
P190 is asstd with
CML
ALL
CML treatment
HU used sometimes
continue TKI indefinitely. COnsider HSCT in chronic phase
for refracgtory chronic you can do higher tki dose or change tiki
for accelerated phase or blast crisis try to induce remission with chemo + TKI then take to HSCT
incidence rate of AML and ALL
2-4 years (80 million cases/million
81% ALL
Whites 2x higher
Leading cause of cancer death <20 years
1970s CNS deemed a sanctuary site
genetic conditions increased risk for ALL
DS, ATM, nijmegan breakage syndrome, bloom (AML), constitutional mismatch repari, rasopathies, kleinfelter, li fraumene (hypodiploid), immunodeficiency
Which gene is overexpressed in DS with ALL
60% overexpress CRLF2, P2Ry8 most common. Favorable prognosis for DS with CRLF2 vs patients with CRLF2 without DS
ALL Risk stratification, SR vs HR
SR: 1-9.9yrs, WBC <50k
HR: 1-10 yrs with WBC >50, >10 years
T ALL slower to clear than B ALL. What time point is prognostic?
MRD at end of consolidation is most prognostic (vs at end of inductino like B ALL )
most important prognostic indicator for infant ALL
KMT2A most common is t(4;11)
poor prognosis especially under 90 days old, more often extramedullary sites
what kind of leukemia has eosinophils over 100,000?
eosinophilia can be reactive, not related to a specific type of
Hypercalcemia is associated with which translocation?
t(17;19)
TCF3:HLF fusion
poor prognosis
Which type of blasts express HLA-DR
almost all b precursors are DR+, most t all are DR-, some AML are DR+
myeloid expression like cd13 and 33 is common in ALL and has no prognostic significance (commonly seen with ETVRUNX1). When does it confer a poor prognosis
when myeloid and lymphoid features are on the same cell
Very poor prognosis when there are distinct populations of lymphoid and myeloid blasts (indicates a more primitive stem cell)
MPAL - AML or ALL therapy?
ALL therapy
Cytogenetics/Gains/losses
Hyperdiploidy:
Low Hypodiploidy
Haploidy
Masked hypoloidy
Hyperdiploidy: gain of 4 and 10 (double trisomy)
Low Hypodiploidy: modal number 32-39 chromosomes
Haploidy: modal number <32 chromosomes
Masked hypoloidy: can masquerade as hyperdiploidy
Ph like ALL deletion of
4 most valuable drugs in remission induction for ALL
steroids
VCR
PEG
Anthracycline
SR ALL treatment overview
4 week induction
4 week consolidation with wkly IT (8 week for HR)
8 week interim maintenance with escalating IV mtx
8 week delayed intensification
maybe 2nd interim maintenance (capizzi for HR)
Maintenance
cranial radiation for CNS3 disease receives 1800 cGY which includes …
posterior halves of the globes of eyes
spinal radiation rarely used
why give HD MTX before cranial radiation for ALL
HD mtx after cxrt is associated with cns toxicity
which day of MRD is most significant predictor of outcome of ALL
day 29
targets:
Inotuzumab
blina
car-t
Inotuzumab: CD22 conjugated to calicheamicin
blina: bispecific CD3 and CD19
car-t: transduced with anticd19 receptor
why must you treat an ALL CNS relapse systemically?
very high chance of BM relapse if you dont treat systemically
When CD34+ levels is over ___ you collect stem cells for transplant
> 20cells/uL
Hematopoietic cell sources:
Autologous transplant:
Allogenic transplant:
Autologous transplant: PBMC, quick engraftment
Allogenic transplant: yet to be determined. bone marrow has intermediate rejection and GVHD. PBMC gives more t cells, rapid engraftment, but more chronic GVHD
Bone marrow is preferred in peds for nonmalignant disorders. Used for high risk procedures: reduced intensity regimens, second transplant
PBSC is preferred for graft manipulation (T cell depletion)
What is the mismatch limit for unrelated donor bone marrow/PBSC
single allele/antigen mismatch (7/8). If there’s more than one mismatch, then need to use post-cy
who gets non myeloablative vs reduced intensity vs myeloablative conditioning in allogenic transplants?
Allogeneic: Myeloablative are superior to RIC for AML/MDS
- Bu/Cy, Bu/Flu
TBI-based are better for ALL
RIC and non ablative better for nonmalignant disorders (RIC for HLH flu/mel/thio) SCID has no prep needed.
Serotherapy (ATG, Campath ) used to reduce GVHD
All autos are getting high dose, myeloablative therapy (NBL, CNS, Lymphoma)
9 mo with HLH s/p transplant with RIC regimen has falling chimerism at day 55+. what is the next step?
wean immune suppression rapidly and follow chimerism
note that in aplastic anemia, bc it’s an autoimmune reponse sometimes in partial chimerism you will increase immune suppression
Which type of T cell is most delayed to recover after transplant
CD4
Agents to prevent GVHD further compromise cd4 recovery:
ATG, pred = lysis
cyclosporine, tacro = inhibit TCR activation, thus early cytokine production
MTX, MMF, siro (mtor inhibitor that inhibits cells cycle) = inhibit clonal expansion and proliferation
T cell absent
T cell broken
SCID
WAS, Hyper IGM, XLP, ALPS
B cell absent
B cell broken
XLA (increased t cells)
CVID (decrease b and t cells, normal CBC)
Neuts absent
Neuts broken
SCN
CGD
Definition of severe aplastic anemia
2/3 peripheral blood criteria: anc<500, plts <20k, retic <1%
and
1/2 bone marrow criteria: <25% cellularity, or up to 50% cellularity with <30% hematopoietic cells
Very severe AA: ANC<200
eosinophilic fascitis and hypogammaglobinemia can be seen with
secondary aplastic anemia
which type of hepatitis can be associated with aplastic anemia?
seronegative (non A-G)
what can you see 5-10 days after starting ATG for aplastic anemia?
serum sicknesss: fever, rash, myalgia, arthralgia, myocarditis, gi/cns/renal
when do you automically dose reduce eltrombopeg for aplastic anemia
Southeast asian ancestry
PNH is d/t acquired somatic mutations in PIG-A gene. How does PIGA function?
it creates an anchor called GPI which binds glycoproteins CD55/59 to cell membrane. If it does not bind cell can undergo complement mediated lysis
diagnosis of PNH
flow to quantitate % of GPI deficient (absent CD55/59) anchored protein on granulocytes and other cell lineages
missing radii but still have thumbs =
missing radii but no thumbs =
TAR
Fanconi anemia
what if you have a high suspicion of fanconi anemia but blood testing breakage analysis is equivocal
repeat breakage testing on cultured skin fibroblasts
you can treat FA with androgens. why do you need to follow LFTs
peliosis hepatis (blood lakes)
pulmonary fibrosis, early greying, dental, hyperhydrosis
dyskeratosis congeniti
there are other features but pulm fibrosis and early greying are commonly tested on boards.
how often do you marrow SDS patients
yearly
ELA-2/ELANE gene
severe congenital neutropenia (ANC<200)
heterozygous mutations with cyclic neutropenia
WHIM syndrome
neutropenia with warts, hypogammaglobulinemia, infections, myelokathexis
AD CXCR4 mutation
HPV susceptibility
age <1 year
macrocytosis
reticulocytopenia
ADA deficiency
mutations in rps and rpl ribosomal proteins
dBA
dba or TEC?
early childhood presentation 1-5 yrs
no physical anomalies
some may have macrocytosis
half will have high plt count
TEC
dba presents under a year with macrocytosis
congenital megakaryocytic thrombocytopenia (CAMT)
AR, c-MPL gene mutations (thrombopoietin receptor) which decreases BM megakaryocytes so thrombocytopenia noted at birth. How do you treat
transplant
RUSAT
radioulnar synostosis with amegakaryocytic thrombocytopenia
how does this differ from CAMT
strong predisposition to early marrow failure (sAA)
screen bilateral forearms, FTT, renal US and echo
TAR
when do you expect them to outgrow thrombocytopenia
by 1 year
look for bilateral absence of radii with thumbs (in FA there is no thumbs)
Pearson Syndrome
refractory sideroblastic anemia by age 6 months – mitochondrial DNA deletion **
marrow shows vauolated precursors/ringed sideroblasts
can look like SDS bc also has pancreatic dysfunction
GATA2 spectrum disorders
monocytopenia, warts
Monocytopenia and mycobacterial infection, monosomy 7 MDS
Most common infection among those with MPO deficiency and diabetes
disseminated Candida
How to diagnose specific granule deficiency
through a smear you will see lack of specific granules and bilobed nuclei then confirmed by electron microsopy and genetic sequencing. It is very rare and d/t defect in the myeloid specific transcription factor ccaat/enhancer biding protein epsilon (CEBPE)
