BMT Flashcards by Kyle Mendonça

cGVHD RF

aGVHD
unmatched donor
unrelated donor
F donor, M recipient
alloimmunization (DSA)
PBSC > BM > cord
TBI
malignant indication

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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)

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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%

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Inotuzumab s/e with HSCT

VOD - 50%

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VOD dx

tender hepatomegaly
weight gain >5%
elevated bili
ascites
thrombocytopenia (transfusion refractory)

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VOD US findings

portal vein decreased/reverse flow
monophasic hepatic vein flow
increased hepatic artery resistance
confirmation of hepatomegaly/ascites

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engraftment syndrome presentation

fever
erythrodermic rash (>25% TBSA)
noncardiogenic pulmonary edema (diffuse pulm infiltrates)
hypoxemia

median onset 9d

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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

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aGHVD RF

CMV donor + recipient neg
older donor
F donor, M recipient
HLA mismatch
lack of manipulation (CD34 selection, a/b depletion)

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TA-TMA RF

CNI (CSA, tac, sirolimus)
TBI
HD Busulfan

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Describe CAR-T mechanism

patient autologous T cells manipulated with specific target fused to TCR so that binding causes automatic T cell activation

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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

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Define 6/6, 8/8, 10/10

6/6: A, B, DRB1
8/8: +C
10/10: +DQB1

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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

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Auto HSCT indications and conditioning

NBl: CEM, Thio/Cy
CNS: carbo/thio
Lymphoma: BEAM

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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)