119.3 ๐Ÿฉบ ๅ…ง็ง‘ๅฐˆ็ง‘่€ƒๅ‰็‰ˆ

119.3.0.1 ๐Ÿ“Œ ไธ€้ ้‡้ปž

  • 22E ้‡ๅคง้€ฒๅฑ•:
    • PTCy ๅœจ matched-related/MUD (BMT CTN 1703 2023)๏ผš่ˆ‡ๆจ™ๆบ– CNI/MTX ๅŒๆ•ˆไฝ† GVHD ้กฏ่‘— โ†“
    • REACH-2 / REACH-3: ruxolitinib ๅฐ steroid-refractory aGVHD/cGVHD ็ขบ็ซ‹ standard
    • Belumosudil (ROCKstar trial): ROCK2 inhibitor for cGVHD
    • Letermovir for CMV prophy ๅ–ไปฃ ganciclovir preemptive ๅœจๅคš centers
    • Exa-cel (CASGEVY) approved 2023 by FDA for SCD + transfusion-dependent thalassemia โ†’ ๅ–ไปฃ allo-SCT for hemoglobinopathies
    • Lovo-cel (LYFGENIA) lentiviral gene addition therapy for SCD approved 2023
    • CAR-T ๅ–ไปฃ allo-SCT ้ƒจๅˆ† indications: DLBCL R/R (axi-cel CARTITUDE, liso-cel TRANSFORM); ALL R/R (tisagen, brexu); MM R/R (Cilta-cel CARTITUDE-4)
    • Microbiome research: dysbiosis โ†‘ GVHD; FMT trials post-HSCT
    • CRISPR/Cas9 + base editing for inborn errors / immunodeficiencies / sickle cell ๆŽข็ดข
    • Newborn screening for SCID + early HSCT (best outcomes)
  • Taiwan: ๅฅไฟ HSCT ๆขไปถ็ตฆไป˜๏ผˆmatched related + MUD๏ผ‰๏ผ›haplo-SCT ๆขไปถๆ“ดๅคง๏ผ›cord blood transplant ๆขไปถ๏ผ›CAR-T (axi-cel, tisa-cel, cilta-cel for DLBCL/ALL/MM) ๅฅไฟ condition๏ผ›exa-cel ่‡ช่ฒป๏ผˆNT $4,000-7,000 ่ฌ๏ผ‰

119.3.0.2 ๐ŸŒŸ Pearls (12)

  1. PTCy mechanism: high-dose Cy 3-4 day post-infusion โ†’ ๆฎบๆœ€ alloreactive T cells๏ผˆๆœ€ proliferating๏ผ‰โ†’ ็•™ less reactive T cells + Tregs๏ผ›ๅฐ haplo + matched ้ƒฝๆœ‰ๆ•ˆ
  2. HLA matching evolution: ๆ—ฉๆœŸ 8/8 ๆ˜ฏ standard๏ผ›้ซ˜่งฃๆžๅบฆ NGS HLA typing ่ญ‰ๅฏฆ matching for HLA-DPB1 + KIR ligand ไนŸๆœ‰ impact
  3. Reduced-intensity conditioning + PTCy: ่€ไบบ (60-75) ไนŸๅฏ transplant๏ผ›reduced TRM ไฝ† โ†‘ relapse โ†’ ้‡ๆ–ฐ risk-benefit calculation per disease
  4. Donor-Specific HLA Antibody (DSA): pre-transplant screening ้‡่ฆ for haplo / mismatched๏ผ›DSA+ ็—…ไบบ graft failure rate 50%๏ผ›treatment: rituximab + plasmapheresis + IVIg
  5. TA-TMA: schistocytes + LDH โ†‘ + thrombocytopenia + AKI๏ผ›ๆฉŸๅˆถ endothelial injury + complement activation๏ผ›ๆฒป็™‚ ๆ› CNI + eculizumab๏ผˆcomplement C5 inhibitor๏ผ‰
  6. SOS / VOD diagnosis: Modified Seattle / Baltimore criteria๏ผ›ALP + bilirubin + ascites + ้ซ”้‡ โ†‘๏ผ›severe SOS โ†’ defibrotide ๆ”น mortality
  7. GVHD biomarkers: ST2, REG3ฮฑ, TNF-R1 โ†’ MAGIC score predicts non-relapse mortality๏ผ›ๅฏๆŒ‡ๅฐŽๆ—ฉๆœŸๅ‡้šŽๆฒป็™‚
  8. Microbiome + GVHD: ๆŠ—็”Ÿ็ด  โ†’ dysbiosis โ†’ ้ซ˜ risk GVHD + mortality๏ผ›multidrug-resistant Enterococcus dominance ๆ˜ฏ marker๏ผ›FMT trials progress
  9. Post-HSCT relapse for AML: DLI (donor lymphocyte infusion) ไป standard for non-aggressive relapse๏ผ›FLT3-ITD AML post-HSCT โ†’ gilteritinib maintenance (MORPHO trial)
  10. Exa-cel mechanism: CRISPR-Cas9 ex vivo edits BCL11A enhancer โ†’ โ†‘ HbF โ†’ โ†“ HbS or sickle pathology๏ผ›single infusion ๅฏ cure๏ผ›conditioning ไป้œ€ (busulfan)
  11. CAR-T + HSCT relationship: post-CAR-T relapse ไปๅฏ allo-SCT๏ผ›ๅ‰ ASCT ๅพŒ CAR-T ไนŸ OK๏ผ›sequencing ๆŽข็ดข
  12. Nipocalimab / efgartigimod for autoimmune cytopenia post-HSCT: anti-FcRn โ†’ IgG โ†“ โ†’ ้ƒจๅˆ† effective for autoimmune complications

119.3.0.3 ๐Ÿ“ Taiwan + ๅฅไฟ

119.3.0.3.1 ่จญๅ‚™ + ๆต็จ‹
  • HSCT centers: ๅฐๅคงใ€ๆž—ๅฃ้•ทๅบšใ€ๅŒ—ๆฆฎใ€ไธญๅœ‹้†ซๅคงใ€้ซ˜้†ซใ€ๅฅ‡็พŽ ็ญ‰
  • Haplo-SCT ๆ™ฎๅŠๅบฆ โ†‘ since 2015
  • Cord blood: ๆ…ˆๆฟŸ้ชจ้ซ“่ณ‡ๆ–™ๅบซ + ๅฐ็ฃ่ก€ๆถฒๅŸบ้‡‘ๆœƒ
  • Bone marrow donor registry (Tzu Chi): 50 ่ฌ + donors
  • Apheresis / G-CSF mobilization routine
119.3.0.3.2 ๅฅไฟ่ฆ†่“‹
  • Allo-SCT (matched related + MUD 8/8 or 7/8): ๆขไปถ็ตฆไป˜
  • Haplo-SCT + PTCy: ๆขไปถๆ“ดๅคง่ฆ†่“‹
  • Cord blood transplant: ๆขไปถ็ตฆไป˜
  • Auto-SCT for MM/lymphoma: ๆขไปถ็ตฆไป˜
  • Conditioning regimens: ๅฅไฟๆถต่“‹ๅคšๆ•ธๆจ™ๆบ– chemo + TBI
  • Cyclosporine, tacrolimus, MTX, MMF: ๅฅไฟ immunosuppressant
  • Ruxolitinib: ๅฅไฟๆขไปถ็ตฆไป˜ for myelofibrosis๏ผ›aGVHD/cGVHD off-label / ่‡ช่ฒป / clinical trial
  • Belumosudil: ่‡ช่ฒป
  • Ibrutinib: ๅฅไฟๆขไปถ็ตฆไป˜ for CLL/MCL/WM๏ผ›cGVHD off-label
  • Defibrotide: ่‡ช่ฒป็‚บไธป๏ผˆ็ฝ•็”จ๏ผ‰
  • Eculizumab: ๆขไปถ็ตฆไป˜ for PNH / aHUS๏ผ›TA-TMA off-label
  • Letermovir: ๅฅไฟๆขไปถ็ตฆไป˜ for CMV prophy post-allo-SCT
  • Acyclovir / Valacyclovir / Ganciclovir / Foscarnet: ๅฅไฟๆขไปถ็ตฆไป˜
  • TMP-SMX: ๅฅไฟ PCP prophy
  • CAR-T: ๅฅไฟๆขไปถ็ตฆไป˜ axi-cel / tisa-cel for DLBCL R/R 2023๏ผ›ALL / MM ๆขไปถๆ“ดๅคง
  • Exa-cel / Lovo-cel: ่‡ช่ฒป๏ผˆ็ฝ•็”จ๏ผ‰
119.3.0.3.3 ๅœจๅœฐๅˆ†ๅธƒ
  • Allo-SCT volumes: ๅ…จๅœ‹ ~ 200-300/ๅนด๏ผˆmatched + haplo + cord๏ผ‰
  • HLA registry: ๆ…ˆๆฟŸ + ๅœ‹้š› (NMDP, BMDW) ้€ฃ็ต
  • Haplo-SCT ๅทฒๆ™ฎๅŠ๏ผŒๅคš็”จ PTCy
  • ๆฑๅ—ไบž medical tourism๏ผš้ƒจๅˆ† SCD/thalassemia ็—…ไบบไพ†ๅฐ HSCT
119.3.0.3.4 ็—…ไบบ่ก›ๆ•™
  • ๆฒป็™‚ๅ‰ fertility preservation๏ผˆ็ฒพๅตไฟๅญ˜๏ผ‰
  • Caregiver 24-7 ๆ”ฏๆด
  • 100 day intensive monitoring + ไน‹ๅพŒ 1-2 yr immunosuppression
  • Long-term follow-up๏ผšsecond cancer + cardio-onc + ๅ…งๅˆ†ๆณŒ + ๅฟƒ็†
  • ๅ…็–ซๅŠ›ๆขๅพฉ + ็–ซ่‹—ๆ™‚็จ‹
  • ็–พ็—… specific ๅพฉ็™ผ็›ฃๆธฌ

119.3.0.4 ๐ŸŽ“ ๅ…งๅฐˆๅฟ…ๆ‡‚ (12)

  1. HLA typing high resolution + DPB1 + KIR ligand impact
  2. Conditioning regimen choice: MA vs RIC vs NMA + disease- + patient-specific
  3. PTCy in haploidentical + matched (BMT CTN 1703)
  4. GVHD prevention strategies: CNI/MTX/MMF/abatacept/PTCy + ATG
  5. aGVHD / cGVHD treatment ladder: steroid โ†’ ruxolitinib (REACH) โ†’ belumosudil/ibrutinib
  6. TA-TMA + eculizumab management
  7. SOS modified Seattle/Baltimore criteria + defibrotide
  8. CMV management: letermovir prophy vs preemptive ganciclovir
  9. Donor-specific HLA Ab (DSA) + desensitization
  10. Microbiome + GVHD + FMT trials
  11. Gene therapy + CRISPR (exa-cel, lovo-cel) for hemoglobinopathies + ๅ–ไปฃ HSCT
  12. CAR-T + HSCT sequencing: post-CAR-T allo-SCT + bridging strategies

119.3.0.5 ๐Ÿ”ฌ ้€ฒ้šŽๆฉŸ่ฝ‰

119.3.0.5.1 PTCy mechanism (cyclophosphamide)
  • ๆ”ปๆ“Š active T cells๏ผˆmax proliferation post-infusion๏ผ‰
  • ็•™ immature/resting T cells + Tregs
  • ไธ้œ€ ATG / CD20-depleting ๅณ้” GVHD prevention
  • Day +3 + day +4 cyclophosphamide 50 mg/kg
119.3.0.5.2 Microbiome + GVHD (Sloan Kettering, Memorial Sloan)
  • Pre-HSCT: Shannon diversity ่ˆ‡ transplant-related mortality ๅๆฏ”
  • ๆŠ—็”Ÿ็ด ๏ผˆmeropenem ็ญ‰๏ผ‰โ†’ rapid loss of diversity
  • VRE / Clostridium difficile expansion
  • FMT trials show dysbiosis reversal + โ†“ aGVHD
119.3.0.5.3 Exa-cel (CASGEVY) ๆฉŸๅˆถ
  • ็—…ไบบ stem cells ๆ”ถ้›† (G-CSF + plerixafor mobilized)
  • Ex vivo CRISPR/Cas9 editing of BCL11A erythroid-specific enhancer
  • Restoration of HbF (ฮณ-globin) โ†’ ่ฃœๅ„Ÿ HbS / ฮฒ-thalassemia mutations
  • Conditioning: high-dose busulfan
  • One-time infusion โ†’ durable HbF
119.3.0.5.4 Bridging post-CAR-T relapse
  • Bispecific antibodies, allo-SCT, repeat CAR-T
  • Sequencing: ๅคš trial ๆŽข็ดข best order of cellular therapies

119.3.0.6 โš ๏ธ ๅ…งๅฐˆๆ˜“้Œฏ้ปž

  • HLA matching ไธๅˆฐ high-resolution NGS โ†’ ๆผ mismatch
  • PTCy ๅ–ไปฃ ATG ไธ่ฉ•ไผฐ็—…ไบบ risk profile โ†’ ้ƒจๅˆ† high-risk subset ไป้œ€ ATG
  • DSA+ ็—…ไบบไธ desensitize ็›ดๆŽฅ transplant โ†’ graft failure
  • TA-TMA ่ชค็‚บ TTP ็ตฆ plasmapheresis โ†’ ไธๆ•ˆ๏ผŒๆ‡‰ๆ› CNI + eculizumab
  • SOS ่จบๆ–ท delayed (ๆ™šๆœŸๆ‰ defibrotide) โ†’ mortality โ†‘
  • Microbiome diversity ไธ่ฉ•ไผฐ โ†’ ้ซ˜ GVHD risk ็—…ไบบไธ็Ÿฅ
  • CMV preemptive ไธๅŠๆ™‚ letermovir โ†’ ้ซ˜ CMV disease risk
  • Steroid-refractory aGVHD ไธๆ› ruxolitinib โ†’ ๅปถ่ชค
  • Exa-cel ไธ่ฉ•ไผฐ fertility preservation ๅ‰ โ†’ fertility ่ญฐ้กŒ
  • Post-CAR-T ็—…ไบบ allo-SCT ไธ่ฉ•ไผฐ โ†’ ๅคฑๅŽป cure ๆฉŸๆœƒ
  • Pre-transplant ไธ่ซฎ่ฉข fertility / ๅฟƒ็† / financial โ†’ ๅคš้ขๅ‘้œ€ๆฑ‚ๆœชๆปฟ่ถณ
  • Late effects ไธ่ฆๅพ‹ follow โ†’ ็ฌฌไบŒ็™Œ็—‡ / ๅฟƒ / ๅ…งๅˆ†ๆณŒ ๆผ่จบ

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