Restrictive Ventilatory Defects Following Hematopoietic Stem Cell Transplant Are Associated With Increased Mortality

Hematopoietic cell transplantation (HCT) can potentially cure hematologic malignancies, but despite advancements in HCT regimens and graft-versus-host disease (GVHD) management, post-HCT complications, remain a major challenge. The epidemiology of post-HCT pulmonary impairment causing restrictive ventilatory defect (RVD) has not been examined. This study investigates the incidence, etiology, and impact of new-onset RVD following HCT on overall survival (OS) and non-relapse mortality (NRM).

We conducted a retrospective review of adult patients who underwent their first allogeneic HCT for primary hematologic malignancies at The University of Texas MD Anderson Cancer Center between February 1999 and March 2018. RVD was defined by a total lung capacity (TLC) <5th percentile of the lower limit of normal. Patient data were analyzed using the Kaplan-Meier method, log-rank tests, and Cox regression models.

Among 3030 patients, 50 had pre-HCT RVD and 1275 developed new pulmonary impairment post-HCT, of which, we found 270 cases of new-onset RVD. The most common causes of post-HCT RVD were respiratory tract infections (23%), interstitial lung disease (15%) and truncal sclerosis (11%). Multivariate analysis indicated increased age (HR 1.03 per year, 95% CI 1.03-1.04, P < .001), matched unrelated donor transplant (HR 1.29, 95% CI 1.04-1.60, P = .02), mismatched related transplant (HR 2.04, 95% CI 1.33-3.14, P = .001), cord blood stem cell source (HR 3.02, 95% CI 2.26-4.05, P < .001), RVD (HR 2.27, 95% CI 1.77-2.90, P < .001) and cGVHD (HR 1.72, 95% CI 1.44-2.05, P < .001) were associated with higher mortality. More severe restriction (HR 4.04, 95% CI 2.83-5.77, P < .001), progressive RVD (5.04, 95% CI 1.88-13.52, P = .001), and RVD onset within 1 year of HCT (HR 2.61, 95% CI 1.72-3.98, P < .001) were associated with higher mortality.

New-onset RVD post-HCT is associated with increased mortality. These findings emphasize the importance of identifying RVD through proactive pulmonary function monitoring to improve post-HCT outcomes.