1.
Non-infectious pulmonary toxicity after allogeneic hematopoietic cell transplantation
Patel, S. S., Ahn, K. W., Khanal, M., Bupp, C., Allbee-Johnson, M., Majhail, N. S., Hamilton, B. K., Rotz, S. J., Hashem, H., Beitinjaneh, A., et al
Transplantation and cellular therapy. 2022
Abstract
Non-infectious pulmonary toxicity (NPT) is a significant complication of allogeneic hematopoietic cell transplantation (alloHCT) and includes idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP) with an overall incidence ranging 1-15% in different case series and variable mortality rates. A registry study of the epidemiology and outcomes of NPT after alloHCT has not been conducted. The primary objective was to assess the incidence of and risk factors for IPS, DAH, and COP; the secondary objective was to assess overall survival (OS) in patients developing NPT. This retrospective study included adult patients who underwent alloHCT between 2008 and 2017 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR®). Multivariable Cox proportional hazards regression models were developed to identify the risk factors for development of NPT and for OS, by including pre-transplant clinical variables and time-dependent variables of neutrophil and platelet recovery, and acute GVHD post-transplant. This study included 21,574 adult patients, with a median age of 55 years. Per the HCT-Comorbidity Index (HCT-CI), 24% and 15% patients had moderate and severe pulmonary comorbidity, respectively. The cumulative incidence of NPT at 1-year was 8.1% (95% confidence interval [95CI], 7.7-8.5%). Individually, 1-year cumulative incidence of IPS, DAH, and COP was 4.9% (95CI, 4.7-5.2%), 2.1% (95CI, 1.9-2.3%), and 0.7% (95CI, 0.6-0.8%), respectively. Multivariable analysis showed severe pulmonary comorbidity, grade II-IV acute GVHD, mismatched unrelated donor and cord blood transplant, and HCT-CI score ≥1 significantly increased the risk of NPT. In contrast, alloHCT performed in ≥2014, non-TBI and TBI-based non-myeloablative conditioning and platelet recovery were associated with a decreased risk. In a landmark analysis at day+100 post-transplant, the risk of DAH was significantly lower in patients who had platelet recovery by day+100. Multivariable analysis for OS demonstrated that NPT significantly increased the mortality risk (HR 4.2, p<0.0001).