Malignant Heme Flashcards
AML poor risk name 4 t( , )
6;9, 11q23, 9;22, 8;16
AML poor risk name 4 deletions/inversions
inv3, del5q or -5, -7, -17
wt NPM1 and FLT3 high AML risk
high risk
AML poor risk mutations (3)
RUNX1, ASXL1, p53
mut NPM1 and FLT3 high AML risk
intermediate
wt NPM1 FLT3 low AML risk
intermediate
intermediate risk translocation AML (1)
t(9;11)
favorable risk AML (4)
t(8;21), inv 16, mut NPM1 alone or FLT3 low, biallelic CEBPA
mut NPM1 with FLT3 low AML risk
low
patient gets 7+3 but too sick for transplant, medication for maintenance
azacitazine pills improves OS
AML 2 years after chemo name the drug and abnormality
topoisomerase or anthracycline; 11q23
AML 5-7 years after chemo and name 3
alkylating agent (cyclophosphamide, busulfan, melphalan)
Hepatic sinusoidal obstruction syndrome (SOS or VOD), symptoms and timeline, US finding, treatment
RUQ pain, ascites, hepatomegaly, elevated bilirubin, weight gain suddenly
<3 weeks from transplant
US liver shows reversed portal flow
Treat with defibrotide and supportive care
vaccine timing post transplant
inactivated upfront
live vaccine 2 years post-transplant
how many days post transplant defines chronic GVHD
100 days
compare and contrast GVHD related lung disease (2 types)
COP- GGO, restrictive PFTS, reduced DLCO, acute or chronic GVHD, treated with steroids
BO- bronchiolitis obliterans, chronic GVHD, narrowing of airways due to fibrosis, obstructive PFTs, treat the underlying GVHD
Chronic GVHD treatments (top 2 then others)
1) Steroids
2) Ruxolitinib JAK2 inhibitors
ibruitinib, alemtuzumab, belumosudil (ROK2 inhibitor), abatacept and others
gilteritinib, what for, timing of treatment, monitoring for 3 severe issues
FLT3 disease relapsed/refractory, differntiation syndrome, QTc, PRES
which drug is for IDH1 and which is for IDH2, side effect to worry about
IDH1 is ivosidenib
IDH2 is enasidenib
Differentiation syndrome
Which anti-rejection drug for transplant causes PRES
tacrolimus
treatment for blastic plasmacytoid dendritic cell neoplasm and MOA
flow findings
tragraxofusp is an anti-CD123 drug
CD4+ CD56+ CD123+ TCL1+
venetoclax and antifungal azoles, what should you do
dose reduce significantly
name a myeloablative conditioning regimen
Cy/TBI
Bu/Cy
BEAM (lymphomas auto)
Melphalan
CBV (carmustine, etoposide, Cy)
who gets myeloablative conditioning regimen
fit and healthy, hematologic malignancies not in CR, autologous transplant
name a non-myeloablative conditioning regimen
fludarabine/TBI
name a reduced intensity conditioning regimen (RIC) and who gets these
Coborbid conditions with good upfront disease control
FLu/Mel
flu/Bu
flu/cy
flu/Bu/thiotepa
flu/treo
CLL criteria to treat
symptoms (weight loss, fever, night sweats, debilitating fatigue)
marrow failure to stage III or IV rai
massive splenomegaly or nodes (very enlarged palpable, >10 cm nodes )
progressive lymphocytosis >50% over 2 months or LDT <6mo
autoimmune complication not responsive to steroids
extranodal involvement
CLL good risk
13q alone (charlie coyle), IGHV mutated
CLL intermediate risk
+12 or normal cytogenetics
CLL poor risk
del17p, del11q, IGHV unmutated, high b2 microglobulin, p53 sequenced, complex karyotype
p53 positive CLL responds best to
BTK inhibitors, venetoclax +/- obinutuzumab
They do not respond well to chemotherapy
name a PI3K inhibitor approved for use in CLL and what is the indication
duvelisib, idelalisib
cause colitis, pneumonitis, hepatotoxicity
3rd line therapy
hairy cell leukemia flow and treatment, common mutation
relapse time after which you could rechallenge
when do you check for response with marrow after treatment
CD19/20+, CD103+, CD11c+
cladribine or pentostatin
BRAF V600E (vemurafenib)
relapse within 2 years, change therapy
4 months after therapy with cladribine, pentostatin sooner (after count recovery)
Who is offered FCR for CLL and what side effect is concerning
young, fit with IGHV mutated for goal of long remission
fludarabine causes AIHA
drug to avoid in CLL with bleeding history or PUD or afib
ibrutinib
the other BTK (acala and zanubrutinb are supposed to have less bleeding and afib)
flow and differentiation of CLL from mantle cell lymphoma
CLL: CD5+ CD23+, CD20 low
Mantle: CD5+ CD20+ CD 23 neg
Cyclin D1 differentiates as it is always positive
ibrutinib, acalabrutinib, zanubrutinib resistance mutations
drug to overcome resistance
C481 mutation of the BTK kinase (grzekcyk)
pirtobrutinib
which CLL drug must you hold before surgery and for how long
BTKs and hold for 7 days before and after
TLS risk stratification in CLL starting venetoclax
outpatient if LN<5 cm and ALC <25k
outpatient with IVF if LN 5-10 cm or ALC<25
inpatient if LN >10 cm or if LN 5-10 and ALC >25
CLL treatment: venetoclax with which drug is first line and which drug is second line
Ven+ obinutuzumab is first line
Ven+ rituximab is second line
CLL related hematologic entities
AIHA
Pure red cell aplasia
ITP
Hypogammaglobuliemia
B-cell prolymphocytic leukemia (B-PLL), immunophenotype and treatment
CD20/19+, CD22+ CD79a+, FMC7+, IgM+, IgK or L+
if p53 + treat with BTK
FCR, BR or BTK inhibitors
venetoclax uptitration plan in CLL
20 mg for 1 week, 50 mg for one week, 100 mg for 1 week, 200 mg for 1 week, 400 mg thereafter
TLS prophylaxis with hydration and allopurinol
if TLS, hold the dose for 1-2 days, give IVF, repeat labs and if resolved resume same dose
if takes >48 hours to resolve, then go down a dose
ibrutinib interactions
cyp3a
avoid grapefruit
do not use if they are on HIV meds that are strong CYP3A inhibitors
dose reduce to 140 mg if moderate inhibitor must be used like fluconazole, voriconazole, diltiazem, verapamil, ciprofloxacin
420 is the normal dose
erythroid CD markers
CD71 and CD235a
myeloid CD markers
cMPO, CD13, CD33, CD117, CD15
stem cell markers CD
CD34, HLA-DR, TdT
monocyte CD markers
CD64, CD14, CD11b, CD11c, lysozyme
megakaryocyte cd markers
CD41 (GPIIb/IIIa), CD61, CD36, CD42b
B lymphoid cd markers
CD19, CD20, CD10, CD22, CD79a
T lymphoid markers
CD3, CD5, CD7, CD1a, CD2, CD4, CD8
NK CD marker
CD56
APML flow findings
CD33+ bright CD13 +, negative CD34 and HLA-DR
First line treatment CML low risk
Imatinib (400 mg) or 2nd gen TKI
First-line treatment CML int or high-risk
2nd gen TKI
nilotinib (300), dasatinib (100), bostutinib (400)
definition of accelerated phase CML
MDACC modifiend criteria
peripheral myeloblasts >15% but <30 %
peripheral pro and myeloblasts >30%
peripheral basophils >20%
thrombocytopenia with count <100k
other cytogenic abn other than just ph+ (trisomy 8, 17q, trisomy 19, ch3 abn
treatment for accelerated phase CML
2nd generation TKI (higher doses than chronic phase) or 3rd gen
or
omacetaxine if progression from CP-CML
define blast phase CML and treatments
peripheral or marrow blasts >30% or extramedullary CML
AML or ALL induction with TKI depending on whether myeloid or lymphoid differentiation
BCR-ABL level should be where after 3-6 months, if not what should be done
at least <10%, if not evaluate adherence, drug interactions, mutation testing, consider BMB. Switch to another TKI. Eval for allogenic HCT.
If BCR-ABL level is not ____ by 12 months, what should be done
<1%, if not then evaluate adherence, drug interactions, mutation testing, consider BMB. Continue with close monitoring or switch to another TKI.
Goal of BCR-ABL level with treatmet
<1% optimal for LT survival
<0.1 for long treatment-free survival (pre-requisite for a trial off of TKI)
CML mutation T315I, TKI choice
use ponatinib, asciminib, omacetaxine
Bosutinib mutations to avoid
V299L, G250E, F317L
Dasatinib mutations to avoid
V229L or F317
nilotinib mutations to avoid
Y253H, E255K F359
asciminib mutations to avoid
A337T, P456S
CML MMR versus MCyR
Define relapse
MMR= major molecular response is BCR-ABL level <0.1
MCyR= mayor cytogenetic response is Ph positive metaphases <35%
loss of hematologic response (cytopenias), loss of CCyR or BCR-ABL >1%, 1 log increase in BCR-ABL transcript level
Criteria for TKI discontinutation trial
Indication to restart treatment while on trial
chronic phase CML only, TKI for 3 years, stable molecular response with BCR-ABL <0.01% for >2 years
monthly monitoring for 6 months, then space out moving forward
loss of MMR BCR-ABL >0.1 should prompt restarting the TKI
Nilotinib risks/se
Qtc monitoring, vascular events (peripheral arterial), pancreatitis
bosutinib risks/se
diarrhea, liver toxicity
dasatinib risks/se
pleural effusions, pulmonary hypertension
imatinib risks/se
fluid retention, GI upset, muscle cramps, rash
ponatinib risk/se
hemorrhage, cardiac arrythmia, CHF, fluid retention, HTN, liver toxicity, pancreatitis, rash
omacetaxine MOA and use
protein synthesis blocker
Approved for use in CP-CMP with T315I mutations, or accelerated phase CML that progressed from CP-CML. Or ne-novo AP-CML with resistance to or intolerance to two or more TKIs.
CML pregnancy risks
TKIs are teratogenic and cannot be given during pregnancy
Patient must be stable on TKI for 3 years with CMR for 2 years prior to safe stop per trials
If BCR-ABL increases to >1% then treatment should be resumed but if pregnant, interferon alpha can be given to try to keep CML under control
asciminib risks/se and use
CP-CML treated with 2 other TKIs or CP with T315I mutation
elevated amylase and lipase/pancreatitis, hypersensitivity, HTN
Ponatinib dose reduction
start at 45 mg daily then if BCR-ABL of 1% or less, reduce the dose to 15 mg daily which reduces side effects
HL stage and risk strat
I one site, II multiple sites only above or below, III multiple sites above and below, IV marrow or extranodal disease
unfavorable risk factors include:
- ESR>50 or >30 if B sx
- Mediastinal mass ratio >0.33
- >3 nodal sites
- bulky disease >10 cm node
Early-stage unfavorable HL treatment
ABVD x2–>PET–>deauville 1-3–> 2 more ABVD and ISRT OR just 4 cycles AVD (RATHL)
if deauville 4-5 escalate to BEACOPP x2 –>PET deauville 1-3 BEACOPP x2
if deauville 4-5 after BEACOPP then refractory disease
late stage HL treatment
also describe the new regimen protocol
ABVD–>PET with deauville 1-3–> AVD x4
ABVD–>PET with deauville 4-5–> BEACOPP x3–>PET–>good–> 1 more BEACOPP
Also BV+ AVD x6 (ECHELON-1) and restage with PET (1-3 observe), 4-5 biopsy.
early stage non-bulky HL
ABVD x2 and ISRT 20 if no high-risk features
ABVD x2–>PET–>deauville 1-3–> 1-2 more ABVD (D1-2 vs D3) and ISRT 30 OR just 4 cycles AVD (RATHL)
if dauville 4–> 2 more ABVD–>PET–> good then radiate
if dauville 5 biopsy
HL in pregnancy treatment
ABVD can be given after the 1st trimester
siltuximab MOA and use
antibody against IL-6 used in castlemans disease that is HHV8 negative
if positive, treat with rituximab
mycosis fungoides/sezary syndrome what is it and how do you treat it by stage
cutaneous T cell lymphoma, sezary is the late stage with blood involvement and lymphadenopathy
IA minimal skin only-local therapy
IB/IIA skin only with >10% BSA skin or skin and systemic
IIB limited tumors-local RT and skin therapy or systemic and RT
III erythema covering 80% BSA treat with systemic and skin
IV is sezary syndrome lymph and blood inv
systemic treatments include mogamulizumab (CCR4 blocker), BV (second line), romidepsin, interferon alpha, MTX, dexarotene, ECP
maintenance after autotransplant in HL criteria
BV if 2 or more
remission less than 1 year
extranodal disease
PET positive at the time of transplant
B sx
>1 salvage regimen
HL approved as second-line treatments or general R/R disease
BV +/- benda or nivo
DHAP
ICE +/- benda or nivo
pembro +/- ICE
GBV
HL only approved in the third-line treatments
bendamutstine
everolimus
lenalidomide
nivolumab
treat MDS with 5q
treatment with lenalidomide in low or int risk MDS
treat CMML with 5q32 translocation aka PDGFRB gene rearrangement or t(5;12) ETV6-PDGFR beta fusion
treat with imatinib
eosinophilia
treat hypoplastic MDS with HLA-DR15
treat with ATG and cyclosporine
AML defining mutations
t(8;21), inv16, t(15;17)
high risk MDS treatment
azacitadine or decitabine or decitabine+cedazuridine(inqovi oral drug)
mutation associated with MDS with ringed sideroblasts
SF3B1, higher platelet count, higher neutrophil counts, and longer EFS compared to WT
Atypical CML
lacks the BCR-ABL fusion, often mutated SETBP1 gene
MDS prognostic risk groups by cytogenetics
good: -Y, 5q, 20q-, normal
int: other not classified
poor: ch 7 abn and >3 abn
in R-IPSS
del11q is very good
good includes 12p
int includes trisomy 8 and 19
poor includes ch3 issues
treat acute GVHD
steroids, methotrexate, cyclosporine
next line ruxolitinib and ATG, alemtuzumab, infliximab, etanercept, sirolimus, cellcept, tocilizumab, pentostatin, calcineurin inhibitors
childhood MDS mutations
SAMD9L monosomy 7, GATA2, CEBPA, RUNX1, DDX41, ETV6, ANKRD26
prevent acute GVHD meds
ppx with cyclosporine and mtx
abatacept T cell modulator for prophylaxis of GVHD in combination with a calcineurin inhibitor and MTX
mutations prognosis in MDS
good SF3B1
poor ASXL1, EZH2, SRSF2, U2AF1, ZRSR2, RUNX1, TP53, STAG2, NRAS. ETV6, GATA2, IDH2, BCOR, FLT3, WT1, NPM1
Juvenile myelomonocytic leukemia (JMML) treatment
azacitadine
myeloma definition
plasma cells >10% + one
elevated calcium
renal insufficiency cr>2
anemia hgb<10 or <2 below LLN
bone lesion
Free light chain ratio >100
or plasma cells >60%
decitabine is particularly useful in MDS with which mutation
p53
smoldering myeloma definition, treat
M-spike >3
Bence-jones >500/24h
marrow plasma cells 10-59%
absence of myeloma-defining events
observation versus PERTHEMA-GEM suggestion of survival benefit from treatment of high risk with lenalidomide/dex (>20% plasma, M spike >2, free light chain ratio >20)
myeloma staging
I= normal beta2 and albumin
II= low albumin
III= high beta 2
R-ISS:
I: ISS I and standard risk chromosomes, normal LDH
II: in between
III: ISS stage III, elevated LDH or high risk FISH
high risk myeloma cytogenetics/FISH
t(4;14), t(14;16), t(14;20), 17p del, 1q21 gain or amp, MYC translocation, 13q, tetrasomies or complex karyotype
DVT ppx in MM on revlemid
ASA 81-325 if <3 points on IMPEDE or 2 by SAVED, if more then start on anticoagulation ppx dose lovenox or DOAC
zolendronic acid renal cut-off , what do you give instead
<30 do not give, give denosumab
good risk cytogenetics/FISH in myeloma
trisomies, t(11;14), t(6;14), hyperdiploidy
daratumumab moa
CD38 antibody
elotuzumab moa and use
Antibody dependent cellular toxicity (ADCC) myeloma drug against SLAM7 which causes NK cells to kill myeloma cells.
for use in RR myeloma only in combination in third line
belantamab mafodotin moa and use
myeloma anti-BCMA antibody conjugated to cytotoxic maleimidocaproyl monomethyl auristatin F, 4th line
selinexor moa and use
myeloma selective inhibitor of nuclear export, relapsed or refractory DLBCL, 4th line
teclistamab moa and use, side effect to worry about
myeloma BITE targeting CD3 and BCMA, CRS and neurologic se
waldenstrom indications for treatment and treatment options, mutation
anemia or TCP, bulky adenopathy or HSM, hyperviscosity syndrome, neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin disease or B symptoms.
treat with BR or RVd or ibrutinib +/- rituximab or zanubrutinib
myd88
POEMS defined and required major criteria and other criteria for diagnosis
polyneuropathy (major), organomegaly, endocrinopathy, M-protein (major), skin changes
1 other: castlemans, sclerotic bone lesion or elevated VEGF
1 minor: organomegaly, volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis/polycythemia
isatuximab moa and use
myeloma via antibody against CD38 in combination with pom and dex in relapsed refractory setting
fedratinib moa and use and risk
myelofibrosis symptom management, JAK2 inhibitor, wernickes encephalopathy
hypereosinophilic syndrome diagnosis and treatment
diagnose: eos >1500 for >6 mo, ruled out other causes, end organ involvement
molecular testing for PDGFRA, PDGFRB, FGFR1, PCM1-JAK2, chronic eosinophilic leukemia NOS
CHIC2 FISH
steroids, hydrea, JAK inhibitors, mepolizumab, alemtuzumab
targeted therapy with imatinib in those who have FIP1L1/PDGFRA or ETV6-PDGFRB (5q31-33)
treat aggressive systemic mastocytosis
mutation and mast cell markers, symptoms
mast cell leukemia definition in comparison
CD117+ CD25+ C-KIT D816V
treat with midostaurin, avapritinib, inf-alpha, cladribine
early bone loss, diarrhea/flushing, rash, headache, HSM
leukemic form has marrow with 20% mast cells, poor prognosis
primary myelofibrosis risk stratification
Dynamic International Prognostic Scoring System (DIPSS), MIPSS
based on age, constitutional symptoms, cytopenias, blast percentage
now they are adding karyotype and mutations
high risk–> eval for transplant
chronic neutrophillic leukemia mutation and symptoms
CSF3R, mature neutrophilic leukocytosis and infiltration, HSM
pacritinib moa and use
JAK2 inhibitor for myelofibrosis with plts <50k (int or high risk)
langerhans cell histiocytosis flow markers, treatment
CD1a+, CD207+ dendritic cell markers
if multifocal disease if BRAF+ treat with vemurafenib, otherwise treat with cobimetinib,
no mutation can also treat with cytarabine or cladribine
ET risk categories and treatment options
very low risk: <60 with no JAK2 or clot (observe unless symptoms)
low risk <60 with JAK 2 no clot (ASA usually)
int risk >60 no JAK2 no clot (ASA and hydrea)
high risk thrombosis or >60 with JAK2 (ASA and hydrea)
Second line includes interferon or anagrelide
extreme thrombocytosis is not in itself an indication for cytoreductive therapy. >1mill should screen for acquired vws and if present, treat with cytoreductive therapy
PV risk strat and treatment
Low risk <60, no clot
high risk clot or >60
ASA for all, hydrea if high risk
second line treatment: peginterferon alfa-2b
MPN with FGFR1 rearrangement
treat with pemigatinib (FGFR1 inhibitor)
TEMPI syndrome what is it and symptoms, lab finding, treatment
telangiectasias, erythrocytosis, monoclonal gammopathy, perinephric fluid collection, intrapulmonary shunting
elevated EPO 10x500x
treated with bortezomib
follicular lymphoma diagnosis
t(14;18), CD19/20+, CD10+, BCL-2
flipi
age, hgb, node areas >4, ldh >uln, stage
tazemetostat moa and use
EZH2 inhibitor for relapsed or refractor follicular lymphoma with an EZH2 mutation with 2 prior therapies or other options . acts as a methyltransferase inhibitor.
Gastric MALT lymphoma with t(11;18) meaning
treat for h. pylori but also give radiation due to less benefit of hpylori treatment alone with this translocation
splenic marginal zone lymphoma, markers and presentation, associated disorder and treatment
splenomegaly, pancytopenia but with lymphocytosis, marrow involvement (no nodes)
CD20+ CD22+, negative for CD5/25/10/103/cyclinD
NOTCH2 and KLR2 mutations
hep c associated–>treat it and lymphoma may regress
other treatment is rituximab or splenectomy
Mantle cell treatment
Indolent CLL form: observe if asymptomatic
Nodal aggressive form:
- transplant candidate: induction chemo (TRIANGLE regimen R-CHOP+ BTKi/RDHA nordic regimen (maxi-CHOP and cytarabine/ritux) + auto transplant + rituximab maintenance +/- BTK maint
Not transplant candidate:
- BR (no maintenance)
2nd line:
- BTK inibitors like acalabrutinib
- lenalidomide ritux
- bortezomib ritux
- ven ritux or ven ibrutinib
3rd line:
- pirtobrutinib or carT (brexucabtagene autoleucel)
Nasal NK/T treatment (19)
early stage: chemo/rads
often asparginase based like
SMILE regimen (steroid, methotrexate, ifosfamide, asparginase, etoposide)
primary effusion lymphoma, associated condition, virus, treatment
HIV and HHV8
R-EPOCH
t cell prolymphocytic leukemia translocation
inv(14)(q11q32), CD2/5/7/52 TCR+
breast implant-associated lymphoma
ALCL anaplastic large cell lymphoma
total capsulectomy and implant removal bilaterally–> follow
incomplete excision, lymph nodes RT+systemic therapy with BV, CHOP etc
plasmablastic HIV associated lymphoma treatment and markers
CD138 ++, neg CD20, often EBV +
EPOCH or HyperCVAD
IT chemo
Post transplant lymphoproliferative disorder PTLD types and presentation and treatment
non-destructive lesions–> reduce intensity of immunosuppression in conjunction with transplant team, add rituximab if needed for partial response
monomorphic (B cell type) treat with rituximab and RI or chemo/immunotherapy such as R-CHOP
monomorphic T cell type: BV+ CHP or CHOP/CHOEP
grey zone lymphoma markers
CD45/pax5/bob1/oct2/cd15/cd20/cd30/cd79a
primary mediastinal BCL diagnosis markers and treatment
c-rel and TRAF-1
treat with R-EPOCH x6 versus R-CHOP+ radiation
DLBCL treatment by stage
Stage I/II non bulky R-CHOP x3 with radiation or R-CHOP x4
Early stage bulky (>7.5 cm) then R-CHOP x6 +/- rads
III/IV R-CHOP x6
burkitt translocation, immunophenotype, and treatment
t(8;14), (2;8), (8;22); cd20/cd22/cd10/bcl6
R-hypercvad + IT chemo
adult T cell leukemia/lymphoma, virus, presentation, smear finding, immunophenotype, treatment
HTLV-1
osteolytic bone lesions with hypercalcemia, liver and skin involvement
CD2/3/4/5+ CD25+ TCR+
smoldering–> zidovudine/interferon
acute disease EPOCH or BV +cy+doxorubicin+pred
second line mogamulizumab
Pulmonary lymphomatoid granulomatosis what is it and treatment
EBV asscoiated lymphoma with multiple pulmonary nodules with lymphocytic invasion of vascular walls on biopsy, granulomatosis.
Stop the immunosuppression medication, treat with chemo-immunotherapy if if is high grade (R-CHOP_
marginal zone treatments
Nodal:
Stage I or II
- radiation and rituximab
Stage III or IV
- BR
- R-CHOP
- rituximab alone in elderly
second line
- acalabrutinib or len ritux
3rd line
- copanlisib or car-t anti cd19(axicabtagene cilolucel)
cart bridge for rr dlbcl
if avaliable, preferred to switch over second line chemo like DHAP
ALL post-induction consolidation
if CR with MRD-:
- then consolidate with blinatumomab +/-TKI then maintenance therapy
- or consolidate and then transplant if high risk with post transplant TKI
if CR with MRD + then allogeneic transplant indicated.
- consolidate with blinatumumab + TKI or TKI beforehand
- post-transplant TKI
if no CR, then relapsed/refractory treatment
ALL induction treatment stratification
AYA vs Adult
Ph+ or negative
Always give IT chemo ppx!
Elderly:
- TKI + steroid +/- vincristine
- steroid and vincristine or POMP
- blinatumomab +/- TKI
blinatumomab moa and use
BITE between CD3 and CD19 which bridges T and ALL cells
relapsed/refractory ALL and MRD+ ALL after induction followed by transplant
relapsed/refractory ALL treatments
blinatumomab (category 1)
inotuzumab ozogamicin
Brexucabtagene autoleucel (adult) tisagenlecleucel (AYA) or multi-agent chemo
then consider HCT
maintenance regimens in ALL
PH+: TKI added, monthly vincristine/prednisone for 2-3 years, may include weekly methotrexate + daily 6MP
Ph-: weekly MTX + daily 6MP + monthly vincristine/pred
or blinatumomab alternating with POMP (6MP vincristine, mtx, pred)
Risk factors and Cytogenetic risk groups in ALL
Generally high risk
- age >35
- WBC >30 in BALL, >100in TALL
- ETP-ALL in TALL
- see below for risk cytogenetics
good risk: hyperdiploidy (trisomies), t(12;21), t(1;19), DUX4
poor risk is:
- hypodiploidly
-p53
-KMT2A
- IgH, HLF, ZNF384, MEF2D rearranged
- BCR-ABL like with JAK-STAT, ABL rearrangements
- antecedent CML or t(9;22) with IKZF1
- iAMP21
- IKZF1
complex karyotype
inotuzumab moa and use, risk to worry about
CD-22 antibody bound to calicheamicin (antibody-drug conjugate)
liver toxicity, increased risk of liver damage and SOS with transplant
gemtuzumab ozogamicin moa and use
CD33 and calicheamicin ADL for AML CD33+ cells
CMV donor mismatch
better if donor is CMV+ and recipient is CMV- as new marrow has antibodies against it due to prior exposure
engraftment syndrome symptoms, timing, treatment
fever and skin rash within a week of transplantation, pulmonary infiltrates, edema, weight gain, liver/kidney dysfunction, encephalopathy. rule out infection, and treat with steroids
late-phase transplant infections
impaired cellular immunity lead to infection risk to aspergillus, PJP, encapsulated bacteria and VZV
which anti-rejection drug can cause a TMA and what testing show
cyclosporine can cause a drug-induced TMA, ADAMSTS13 is not very low like in TTP, stop the drug or reduce dose, +/- plasma exchange or infusion
MRD for ALL sensitivity requirement
10^-4, 6-color flow cytometry
PCR/NGS is 10^-6
T ALL relapsed refractory treatment
nelarabine +/- etop + cyclophos
angioimmunoblastic T-cell lymphoma presentation and immunophenotype, treat
rash, fluid retention, lymphadenopathy, hypergammaglobulienmia, HSM, eosinophilia, hemolytic anemia
T cell lymphoma that is CD4+, CD8+ with perivascular infiltrates
BV +CHP vs CHOP
loncastuximab tersirine-lpyl moa and use
CD19 antibody drug conjugate with alkylating agent for relapsed or refractory DLBCL
CAR-T matching by disease site and target
Brexucabtagene
Axicabtagene
Tisagenlecleucel
Lisocabtagene
Idecabtagene
ciltacabtagene
Brexucabtagene- BALL, Mantle (BAD)
Axicabtagene- Follicular, Marginal and DLBCL/PMBCL
Tisagenlecleucel- (T)eens with BALL, follicular, DLBCL (3rd line)
Lisocabtagene- DLBCL, PMBCL
Idecabtagene- myeloma (4 or more lines)
ciltacabtagene- myeloma (4 or more lines)
CD19 for lymphomas, BCMA for myeloma car-t
occular MALT lymphoma treament options and associated bug
chlamydia psittaci, treat with doxycycline which can cause regression
or radiation or surgery or rituximab
mantle cell maintence after AST
rituximab +/- BTK with OS benefit
romidepsin moa and use
HDAC- histone deacetylase inhibitor approved for yse in cutaneous T-cell lymphoma
erdheim chester disease what is it and treatment
non-langerhans histiocytic disorder
infiltrative disease into bone and other tissues
with or without mapK mutation can be treated with cobimetinib
BRAF V600E MUTATIONS: vemurafenib
other: cytarabine or cladribine without mutation
polatuzumab moa and use
ADC targeting CD79b on B cell receptor which is used in DLBCL
tafasitamab-cxix moa and use
CD19 antibody given with lenalidomide in refractory DLBCL third line or later
follicular lymphoma treatment lines
BR
R2
3rd line- copanlisib, tazemetostat, car-t or mosuntuzumab
Mosuntuzumab moa and use
BITE between CD3 and CD20 approved in FL after 2 or more lines of therapy
copanlisib moa and use and risk
PI3K inhibitor alpha and delta 3rd line for R/R follicular lymphoma, look out for elevated glucose
High risk cytogenetics in amyloid and why
t(11;14) due to bortezomib resistance
treatment first line is dara-CyBorD
this is a good risk cytogenetic profile in myeloma however
11;14 in myeloma sensitive to what
venetoclax which is given with dex with or without dara or PI
cryoglobulins in myeloma or waldenstoms, symptoms and type
type I which are IgG or IgM
cause hyperviscosity and thrombosis such as raynauds, digital ischemia, livedo reticularis and neurologic symptoms
treat underlying disorder, avoid cold
Transthyretin TTR amyloidosis treatment
progressive cardiomyopathy
liver transplant
tafamidis- binds TTR and reduces amyloid formation
Inotersen- oligonucleotide inhibitor of hepatic TTR production for neuropathy
patisiran- siRNA prevents TTR production by the liver, approved for neuropathy improvement
