Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation

Abstract

A B S T R A C T Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV 1 ) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

“…Additional endothelial injury syndromes after alloSCT not addressed in this overview include i.a. vascular type idiopathic pneumonia syndrome [ 5 ], early fluid retention [ 6 ], early bilirubinaemia [ 7 ] posterior reversible encephalopathy syndrome, and several subtypes of chronic GVHD [ 8 ].

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Pulmonary Complications in Hematopoietic Stem Cell Transplant Recipients—A Clinician Primer

“…Diffuse alveolar hemorrhage (DAH) has similar rates in both allogeneic (3–7%) and autologous (1–5%) HSCT recipients [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. While classically considered an early pulmonary complication occurring within a month of transplant, up to 30% of cases of DAH occur >100 days post-transplantation [ 20 ].…”

“…Idiopathic pneumonia syndrome (IPS) represents a spectrum of diseases occurring between 20 and 42 days post-transplant, with the range extending up to 100+ days post-transplant. It is more common in allogeneic HSCT recipients [ 22 ]. Myeloablative conditioning with high-dose total body irradiation and acute GVHD are major risk factors for IPS development [ 24 , 25 , 26 , 27 ].…”

“…High-dose corticosteroids continue to be the treatment of choice with variable response. Up to 85% of IPS cases are non-responsive to corticosteroids and progress to respiratory failure with up to 90% requiring mechanical ventilation [ 22 , 28 ]. Overall, IPS has a very poor prognosis with 60–80% case fatality [ 22 , 28 , 29 , 30 ].…”

“…Up to 85% of IPS cases are non-responsive to corticosteroids and progress to respiratory failure with up to 90% requiring mechanical ventilation [ 22 , 28 ]. Overall, IPS has a very poor prognosis with 60–80% case fatality [ 22 , 28 , 29 , 30 ]. The addition of etanercept has demonstrated promising early results with an overall improvement of 2-year survival although follow-up studies have suggested less durable benefit [ 30 , 31 , 32 ].…”