Abstract Introduction Pulmonary complications after stem cell transplantation (SCT) are a major cause of morbidity and mortality. While non-infectious etiologies such as chronic lung graft versus host disease (GVHD) typically present as bronchiolitis obliterans, an irreversible obstructive process, the development of restrictive lung disease following SCT is less well characterized. We present a patient after allogenic SCT who developed progressive interstitial fibrosis after COVID-19 infection. Case report A 17-year-old male underwent 10/10 HLA matched sibling SCT for relapsed leukemia following conditioning with fludarabine, thiotepa, and total body irradiation. Early post-transplant course was complicated by liver veno-occlusive disease treated with defibrotide, but there was no evidence of acute GVHD in the first 100 days. Seven months post-transplant, he developed a respiratory COVID 19 infection. Despite treatment with nirmatrelvir/ritonavir and documented viral clearance, cough and shortness of breath progressed. Imaging revealed extensive ground glass opacities (GGO) and pneumomediastinum. He was treated with non-invasive bi-level ventilation, etanercept, and methylprednisolone burst (∼2mg/kg) with quick wean. After a month-long admission, he was discharged on 1LPM supplemental oxygen. Within a week, he was again admitted for worsening dyspnea on exertion and knee pain. A maternal history of Sjogren’s syndrome with pulmonary fibrosis prompted an unrevealing rheumatologic evaluation. Bronchoscopy with lavage and lung cryobiopsies of ground glass opacification in left subsegments revealed patchy interstitial fibrosis without evidence of inflammation or infection. Repeat CT imaging showed progressive interstitial fibrosis with improvement in GGO, mild bronchiectasis, and persistent pneumomediastinum. Pulmonary function testing showed reduced diffusion capacity (44%) and slow vital capacity (42%). Six-minute walk (6MW) distance was 209 meters with desaturation despite oxygen support. Following multidisciplinary discussions, his steroid regimen was increased to 1mg/kg/day with a slow taper ( 10% decrease/week) and addition of pirfenidone due to elevated tumor necrosis factor alpha levels. On increased steroids, 6MW distance increased to 343 meters a week later. Three weeks later, he was able to wean off supplemental oxygen. Repeat lung function testing is pending. Discussion This case highlights the complex interplay between infectious and non-infectious pulmonary complications following SCT. To what extent interstitial fibrosis developed due to COVID infection versus alloreactivity post SCT or both is unclear. Whether restrictive lung pathology occurring in isolation, without other manifestations of chronic GVHD, represents true GVHD-related involvement also remains unclear. Optimal management requires a multidisciplinary approach, with close collaboration between the pulmonary and transplant teams to help guide diagnosis, treatment, and long-term follow- up. This abstract is funded by: none
Sunkad et al. (Fri,) studied this question.