Early Post-Transplantation Spirometry Is Associated with the Development of Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (allo-HCT) is often diagnosed at a late stage when lung dysfunction is severe and irreversible. Identifying patients early after transplantation may offer improved strategies for early detection that could avert the morbidity and mortality of BOS. This study aimed to determine whether a decline in lung function before and early after (days +80 to +100) allo-HCT are associated with a risk of BOS beyond 6 months post-transplantation. In a single-center cohort of 2941 allo-HCT recipients, 186 (6%) met National Institutes of Health criteria for BOS. Pretransplantation and post-transplantation day +80 spirometric parameters were analyzed as continuous variables and included in a multivariable model with other factors, including donor source, graft source, conditioning regimen, use of total body irradiation, and immunoglobulin levels. Pre-transplantation forced expiratory flow between 25% and 75% of maximum (FEF 25-75 ), day +80 forced expiratory volume in 1 second (FEV 1 ), and day +80 FEF 25-75 had the strongest associations with increased risk of BOS. Assessment of the multivariable model showed that a decline in day +80 FEF 25-75 added additional risk to the day +80 FEV 1 model (P = .03), whereas FEV 1 decline at day +80 added no additional risk to the day +80 FEF 25-75 model (P = .645). Moreover, day +80 FEF 25-75 conferred additional risk when considered with pretransplantation FEF 25-75 . These results suggest that day +80 FEF 25-75 may be more important than FEV 1 in predicting the development of BOS. This study highlights the importance of obtaining early post-transplantation pulmonary function tests for the potential risk stratification of patients at risk for BOS.

Noninfectious lung complications of hematopoietic cell transplantation

“…27 The cur rent inci dence is approx i ma tely 3% in pedi at ric and 3% to 6% in adult HCT. 1,[51][52][53] A chal lenge of this dis ease has been its insid i ous nature lead ing to mod er ate decline at diag no sis. The fre quent use of home devices to detect early de clines in lung func tion and the use of FEF25-75 as an indi ca tor may aid in the ear lier iden ti fi ca tion of BOS.…”

“…The fre quent use of home devices to detect early de clines in lung func tion and the use of FEF25-75 as an indi ca tor may aid in the ear lier iden ti fi ca tion of BOS. 52,54,55 Newer imag ing and serum mark ers show prom ise for BOS diag no sis, includ ing para met ric response map ping (with recent data for machinelearn ing algo rithms), xenon129 mag netic res o nance imag ing (MRI), and serum MMP3, though the data are insuf fi cient to replace PFTs. [56][57][58][59] This may be most crit i cal for chil dren who can not per form PFTs in the future.…”

Incidence and impact of community respiratory viral infections in post‐transplant cyclophosphamide‐based graft‐versus‐host disease prophylaxis and haploidentical stem cell transplantation

“…Application of prevention and treatment strategies may be more effective once the important deficits in immune recovery are better defined. Pro‐active surveillance, aggressive efforts to limit the incidence of CRVIs, including wearing masks, and detection of early disease may offer opportunities to intervene and prevent adverse outcomes related to the immunological sequelae of CRVIs in these patients 32,38–41 …”

Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions

“…GVHD-BOS usually develops between 100 days and 2 years of HSCT, but onset beyond 5–6 years post-HSCT has been noted, usually in patients experiencing an extrapulmonary GVHD flare [ 7 , 16 , 17 ]. Risk factors for GVHD-BOS are impaired lung function before and early after HSCT, a myeloablative/busulfan-containing conditioning regimen, CMV seropositivity, pre-transplant history of pulmonary disease, female donor, unrelated donor and prior acute GVHD; receipt of antithymocyte globulin, which decreases chronic GVHD risk, reduces the risk of BOS [ 17 , 18 , 38 ].…”