Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease

Abstract

Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious, and often fatal lung alloreaction that can occur following allogeneic hematopoietic stem cell transplantation (HSCT) or allogeneic lung transplantation. Current estimates in the literature suggest that approximately 2% to 3% of all allogeneic HSCT recipients and 6% of patients who develop chronic graft-versus-host disease (cGVHD) will develop this syndrome. However, based on newer data it is likely that the true incidence of BOS is higher. Unfortunately, the survival and treatment of patients with BOS after HSCT has not improved over the last 20 years. Attempts at clinical trials have been hindered by the lack of uniform diagnostic criteria and inability to detect the syndrome at a reversible stage in its natural history. Recently, the National Institutes of Health (NIH) consensus project for criteria in cGVHD has made recommendations regarding the diagnosis of BOS and monitoring of lung disease among long-term survivors. Although a rare and poorly understood manifestation of cGVHD, BOS occurs commonly after lung transplantation and is similar in pathology, clinical presentation, radiographic presentation, and presumed immunologic pathogenesis. This review describes the current understanding of the epidemiology and pathogenesis of BOS and presents information on evaluations and therapies for patients with BOS after HSCT.

Figure 1. Survival curves showing cumulative freedom from major adverse events (death or necessity for re-transplantation) of lung transplant recipients stratified by their CD28 expressions

Left panel: Major adverse event-free survival of CD28% High (n = 46) and CD28% Low (n = 19) among all recipients (including subjects with either BOS and no evidence of rejection). CD28% High denotes subjects with CD4⁺CD28⁺/CD4⁺_Total ≥0.90. CD28% Low denotes subjects with CD4⁺CD28⁺/CD4⁺_Total <0.90. Values for CD28% among non-transplanted healthy, age-matched normal individuals are ~0.98 ± 0.02. Tick marks denote interval censored events, and numbers in parenthesis at end of the survival curves denote remaining, unafflicted subjects that were censored at 24 months of observation. Comparisons were made by log-rank. Right panel: Survival curves showing cumulative freedom from major adverse events of CD28% High (n = 24) and CD28% Low (n = 16) among the recipients with BOS. Reprinted from reference[56] with permission.

Figure 2

Hypothetical Spirogram and Flow Volume Curves for Bronchiolitis Obliterans Syndrome. Copied with permission from Journal of American Medical Association[70]