Diagnoses, key points, and treatments of noninfectious lung injury after HCT
| Diagnosis . | Peak time post HCT/structure . | Key findings . | Additional diagnosis . | Proposed treatments . |
|---|---|---|---|---|
| DAH | <day 30 post HCT endothelial | Hypoxia, new infiltrate, bloody BAL | Hemosiderin-laden macrophages | Inhaled transexamic acid, intrapulmonary recombinant factor VIIa |
| PERDS (IPS) | Pre-engraftment Alveolar (from endothelial damage) | Respiratory distress/hypoxia | Multilobar infiltrates | Steroids/etanercept |
| CLS (IPS) | Engraftment to day 15 Alveolar (from endothelial damage) | Dyspnea/hypoxia, >3% weight gain | Multilobar infiltrates | Steroids/etanercept |
| AIP and toxin-related lung injuries, DPTC | 50 days post HCT Alveolar | Fever, dyspnea, cough | Ground glass on imaging/bilateral infiltrates, restrictive PFT | |
| IPS (PERDS, CLS, DAH, AIP, DPTC) | 45 days post HCT Alveolar | Hypoxia, pulmonary infiltrates | Steroids/etanercept | |
| CRS | <7 days postcellular therapy Alveolar | Respiratory compromise, hypoxia | Infiltrates | Tociluzumab |
| PVOD, PCT, TA-TMA | 15-120 days post HCT Endothelial | Hypoxia, dyspnea, vascular occlusion, may progress to pulmonary hypertension Biopsy diagnosis | Sildenafil (PVOD, TA-TMA), nitric oxide (TA-TMA) prostacyclins, calcium channel blockers (PVOD) Steroids (PCT)? | |
| RLD after HCT | Day 100-1 year Alveolar | Decreased FEV1, normal FEV1/VC ratio, fibrosis on CT (upper lobes) | PPFE, NSIP interstitial pneumonia; can include other diagnoses | Etanercept Poor response to steroids |
| BOS | Day 100-1.5 years Airway | FEV1 < 75%, ≥10% decline, FEV1/VC LL of the 90% CI, absence of infection and either preexisting cGVHD, air trapping by expiratory CT or by PFT, or circumferential fibrosis of bronchioles on biopsy | Newer modalities: PRM and xenon-129 MRI | FAM: inhaled fluticasone, azithromycin, montelukast +1 mg/kg/d prednisone with rapid taper; ECP, etanercept, GERD tx, nutrition, infection prophylaxis |
| Non-HCT-specific complications: TRALI/TACO, PE, ARDS, A1AT, cancer/PTLD, pneumothorax | Alveolar (ARDS, PTLD) Airway (A1AT) Endothelial (TRALI/TACO, PE) | TRALI/TACO: temporal association blood products, fever, acute dyspnea PE: dyspnea/hypoxia, V/Q+ ARDS: fever, dyspnea, hypoxia, bilateral infiltrates | A1AT: obstructive disease, emphysema, bronchiectasis PTLD: nodules/EBV+ | TRALI/TACO: supportive care PE: anticoagulants ARDS: treat underlying cause (often antimicrobial) and supportive care A1AT: A1AT infusion, inhaled steroids PTLD: rituximab, cellular therapy Pneumothorax: chest tube |
| Diagnosis . | Peak time post HCT/structure . | Key findings . | Additional diagnosis . | Proposed treatments . |
|---|---|---|---|---|
| DAH | <day 30 post HCT endothelial | Hypoxia, new infiltrate, bloody BAL | Hemosiderin-laden macrophages | Inhaled transexamic acid, intrapulmonary recombinant factor VIIa |
| PERDS (IPS) | Pre-engraftment Alveolar (from endothelial damage) | Respiratory distress/hypoxia | Multilobar infiltrates | Steroids/etanercept |
| CLS (IPS) | Engraftment to day 15 Alveolar (from endothelial damage) | Dyspnea/hypoxia, >3% weight gain | Multilobar infiltrates | Steroids/etanercept |
| AIP and toxin-related lung injuries, DPTC | 50 days post HCT Alveolar | Fever, dyspnea, cough | Ground glass on imaging/bilateral infiltrates, restrictive PFT | |
| IPS (PERDS, CLS, DAH, AIP, DPTC) | 45 days post HCT Alveolar | Hypoxia, pulmonary infiltrates | Steroids/etanercept | |
| CRS | <7 days postcellular therapy Alveolar | Respiratory compromise, hypoxia | Infiltrates | Tociluzumab |
| PVOD, PCT, TA-TMA | 15-120 days post HCT Endothelial | Hypoxia, dyspnea, vascular occlusion, may progress to pulmonary hypertension Biopsy diagnosis | Sildenafil (PVOD, TA-TMA), nitric oxide (TA-TMA) prostacyclins, calcium channel blockers (PVOD) Steroids (PCT)? | |
| RLD after HCT | Day 100-1 year Alveolar | Decreased FEV1, normal FEV1/VC ratio, fibrosis on CT (upper lobes) | PPFE, NSIP interstitial pneumonia; can include other diagnoses | Etanercept Poor response to steroids |
| BOS | Day 100-1.5 years Airway | FEV1 < 75%, ≥10% decline, FEV1/VC LL of the 90% CI, absence of infection and either preexisting cGVHD, air trapping by expiratory CT or by PFT, or circumferential fibrosis of bronchioles on biopsy | Newer modalities: PRM and xenon-129 MRI | FAM: inhaled fluticasone, azithromycin, montelukast +1 mg/kg/d prednisone with rapid taper; ECP, etanercept, GERD tx, nutrition, infection prophylaxis |
| Non-HCT-specific complications: TRALI/TACO, PE, ARDS, A1AT, cancer/PTLD, pneumothorax | Alveolar (ARDS, PTLD) Airway (A1AT) Endothelial (TRALI/TACO, PE) | TRALI/TACO: temporal association blood products, fever, acute dyspnea PE: dyspnea/hypoxia, V/Q+ ARDS: fever, dyspnea, hypoxia, bilateral infiltrates | A1AT: obstructive disease, emphysema, bronchiectasis PTLD: nodules/EBV+ | TRALI/TACO: supportive care PE: anticoagulants ARDS: treat underlying cause (often antimicrobial) and supportive care A1AT: A1AT infusion, inhaled steroids PTLD: rituximab, cellular therapy Pneumothorax: chest tube |
EBV, Epstein-Barr virus; ECP, extracorporeal photopheresis; FAM, inhaled fluticasone, azithromycin, and montelukast + 1 mg/kg/d steroid burst and rapid taper; GERD tx, gastro-esophageal reflux disease treatment; PRM; parametric response mapping; V/Q, ventilation/perfusion scan.