BMT Flashcards
cGVHD RF
aGVHD
unmatched donor
unrelated donor
F donor, M recipient
alloimmunization (DSA)
PBSC > BM > cord
TBI
malignant indication
HSCT related CMV tx and tox
reduce immunosuppression
Valganciclovir - graft rejection/myelosuppression, HTN, renal
Foscarnet - NVD, renal/lytes
Cidofovir
IVIG (if pneumonitis)
Letermovir (new, phase II data)
Tisagenlecleucel Maude study outcomes
phase 2, CAR-T R/R ALL
3mo remission rate 81%
6mo EFS 73%, OS 90%
12mo EFS 50%, OS 76%
Inotuzumab s/e with HSCT
VOD - 50%
VOD dx
tender hepatomegaly
weight gain >5%
elevated bili
ascites
thrombocytopenia (transfusion refractory)
VOD US findings
portal vein decreased/reverse flow
monophasic hepatic vein flow
increased hepatic artery resistance
confirmation of hepatomegaly/ascites
engraftment syndrome presentation
fever
erythrodermic rash (>25% TBSA)
noncardiogenic pulmonary edema (diffuse pulm infiltrates)
hypoxemia
median onset 9d
pulmonary cGVHD manifestations and tx
-vbronchiolitis obliterans (fibrotic occlusion of small airways)
- BOOP: PFT obstruction, air trapping, bronchiectasis
- Idiopathic pneumonia syndrome
- diffuse alveolar hemorrhage
FAM = fluticasone, azithromycin, montelukast
ruxolitinib
aGHVD RF
CMV donor + recipient neg
older donor
F donor, M recipient
HLA mismatch
lack of manipulation (CD34 selection, a/b depletion)
TA-TMA RF
CNI (CSA, tac, sirolimus)
TBI
HD Busulfan
Describe CAR-T mechanism
patient autologous T cells manipulated with specific target fused to TCR so that binding causes automatic T cell activation
MHC Class I and II antigens
Class I: A, B, C
- expressed on all cells
Class II: DR, DP, DQ
- expressed on professional Ag presenting cells
Define 6/6, 8/8, 10/10
6/6: A, B, DRB1
8/8: +C
10/10: +DQB1
Target stem cell dose for each source
BM/PB: >4-8 x 10^6 CD34/kg
Haplo: >10-20 x 10^6
Cord: >4 x 10^7 TNC/kg
CD34 selection: >5-20 x 10^6 CD34/kg
Auto HSCT indications and conditioning
NBl: CEM, Thio/Cy
CNS: carbo/thio
Lymphoma: BEAM
DMSO toxicity (auto HSCT)
HTN
bitter taste
NV
headache
rare: encephalopathy, renal, arrhythmias
HSCT infections
- pre-engraftment
- post-engraftment
pre: HSV, candida, aspergillus, viridans group strep, GN bacteria, CONS
post: adenovirus, CMV, ZVZ, late aspergillus
auto HSCT related MDS epi, RF
5-10%, usually 4-7y post
RF: etop, TBI
VOD RF
Busulfan
Cy > 120 mg/kg
TBI > 14 Gy
CSA > Tac
PB > BM > cord
Allo > auto
prior gemtuzumab/inotuzumab
infection (esp pre-existing viral hepatitis)
Conditioning
- SAA
- ALL
- AML
- JMML
- SCD
- HLH
- SAA: Cy/ATG
- ALL: TBI/cyclo +- thio, etop, flu
- AML: Bu/Flu or Bu/Cy
- JMML: Bu/Cy/Mel
- SCD: RIC; campath/TBI
- HLH: RIC; campath
Delayed HSCT complications + monitoring
Eye: eye, retinopathy - annual optho
Dental: root anom, microdontia - dental q6mo
Pulm: IPS, DAH, BO, BOOP - PFT 1y post BMT
Endo: thyroid, growth delay, gonadal failure - yearly TSH, growth, sex hormones at 13F/14M
Cardiac: CHD, arrhythmias - echo q1-5y
Renal: CKD, TA-TMA - UA/lytes day 100, annual BP
CNS: neurocognitive
SMN
Graft rejection RF
RIC
cell dose
HLA mismatch
mixed chimerism
cord source
nonmalignant disorders
hyperinflammatory state
infection, viral reactivation
graft rejection management
reduce immunosuppression
DLI
CD34 boost
3 methods of T cell depletion
CD 34 selection
a/b depletion
in vivo T cell depletion (ATG, campath, PT Cy)
classic (acute) GVHD staging
skin: macpap rash
- grade 1: <25% BSA
- grade 2: 25-50% BSA
- grade 3: >50% BSA
- grade 4: generalized erythroderma
GI: secretory diarrhea
- grade 1: 0.5-1 L/d
- grade 2: 1-1.5 L/d
- grade 3: 1.5-2 L/d
- grade 4: >2 L/d
liver: elevated conjugated bili
- grade 1: bili 2-3 mg/dL (35-50 uM)
- grade 2: bili 3-6 mg/dL (51-100)
- grade 3: bili 6-15 mg/dL (101-255)
- grade 4: bili >15 mg/dL (>255)
classic (acute) GVHD grading
Grade 1: skin I-II only
Grade 2: skin III, liver or gut I
Grade 3: liver or gut II-III
Grade 4: any IV
cGVHD features
skin: sclerotic (lichen planus, scleroderma), poikiloderma
mouth: dry
GI: ulcerations, sclerosis
Liver: elevated bili
Resp: BOOP
aGVHD tx by grade
grade 1: topical steroid, optimize immunosuppression
grade 2+
- methylpred 1-2 mg/kg/d BID x7-14d
- steroid refractory: ruxolitinib and others
cGVHD tx
pred 1 mg/kg/d x6w then eod, usual duration 2y
steroid refractory: ruxolitinib, ibrutinib, MMF, MTX, ritux, etc
VOD EBMT criteria, Seattle Criteria, Baltimore Criteria
EBMT: 2 of
- unexplained consumptive thrombocytopenia
- unexplained w loss >5% over 3 days
- hepatomegaly
- ascites
- bili rising 2+ mg/dL over 3 days
Seattle: 2 of
- bili >2 mg/dL (34.2)
- hepatomeg or RUQ pain
- W gain >2%
Balitmore: bili > 2mg/dL plus 2 of
- tender hepatomeg
- ascites
- W gain >5%
- plt refractoriness
VOD proph, tx
proph: RIC, Tac > CSA, urdodiol
Defibrotide
supportive: maintain euvolemia, remove hepatotoxic meds, transfusions (>30 on defibrotide)
refractory: FFP, antithrombin, etc
TA-TMA screening criteria:
3+ of
- anemia
- thrombocytopenia
- elevated LDH
- schistocytes
- refractory HTN
- proteinuria 1+ mg
TA-TAM dx criteria
biopsy proven
4+ of following present 2x over 2w:
- anemia
- thrombocytopenia
- elevated LDH
- urine Pr:Cr 1+
- HTN
- schistocytes
- elevated sC5b-9
Describe TA-TMA
endothelial damage leading to fibrin deposition and microvascular thromboses, MAHA, plt consumption. Impacts kidney primarily, also resp, GI, neuro
CRS features, ix, tx
fever, hypotension, hypoxia, capillary leak, rash, tachycardia, coagulopathy
elevated ferritin, CRP, IL-6, IL-10, IFNg
tocilizumab +- steroid (limit in CAR-T)
