Clinical Pearls & Morning Reports
Published September 6, 2023
Pulmonary complications after hematopoietic stem-cell transplantation (HSCT) may progress rapidly and are associated with substantial morbidity and mortality. Read the NEJM Clinical Problem-Solving Article here.
Q: How common are serious pulmonary complications during the year after HSCT?
A: Approximately 15,000 patients undergo HSCT annually in the United States, and transplant recipients are increasingly encountered in both academic and community-based settings. An estimated 30% of HSCT recipients have pulmonary complications in the year after transplantation that are associated with substantial morbidity and mortality. Infections account for approximately half of such complications, and recipients of allogeneic transplantation and myeloablative conditioning regimens have the highest risk.
Q: How should the differential diagnosis of a pulmonary complication after HSCT be constructed?
A: Because pulmonary complications of HSCT occur in a somewhat predictable manner, mediated by the ablation and subsequent reconstitution of the immune system, it is important to consider the timing of the complication relative to the transplantation to help narrow the differential diagnosis.
A: Idiopathic pneumonia syndrome is a diagnosis of exclusion composed of several subtypes. It is characterized by widespread alveolar injury in the absence of identifiable infection, cardiac dysfunction, kidney failure, and fluid overload. Although idiopathic pneumonia syndrome was initially thought to occur in up to 15% of HSCT recipients, more recent estimates in the era of reduced-intensity and nonmyeloablative chemotherapy suggest an incidence below 5%. Among these patients, approximately one third have periengraftment respiratory distress syndrome, a subtype that typically occurs within 5 days after engraftment and is characterized by fever, noncardiogenic pulmonary edema, and sometimes rash. Risk factors for idiopathic pneumonia syndrome include the use of myeloablative conditioning with total-body irradiation, an age older than 40 years, female sex, the use of cyclophosphamide or granulocyte colony-stimulating factors, and underlying acute leukemia or myelodysplastic syndrome.
A: The earliest pulmonary complications after HSCT (those that occur before neutrophil engraftment) are most often due to infections. After engraftment (2 to 3 weeks after transplantation), neutrophil and lymphocyte counts recover, providing some protection against infection. During the early postengraftment period (3 to 12 weeks after transplantation), periengraftment respiratory distress syndrome and other forms of idiopathic pneumonia syndrome warrant particular consideration. During the late post-transplantation period (≥4 months after transplantation), pulmonary complications such as bronchiolitis obliterans (a form of chronic graft-versus-host disease) and infections related to maintenance immunosuppression should be considered.