https://orcid.org/0000-0001-9372-5286
TO THE EDITOR:
DeFilipp et al published a phase 2, multicenter, trial treating bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation with ruxolitinib,1 a therapy for other chronic graft-versus-host diseases (cGVHDs).2 The authors should be lauded for undertaking an interventional BOS trial, a rare complication of hematopoietic cell transplantation.3 However, the trial incorporated an atypical definition of BOS, which pertained to 33% of those accrued, our point of discussion.1
Before 2005, 10 distinct BOS definitions confounded the literature.4 The landscape was transformed by the 2005 cGVHD diagnostic criteria,5 refined in 2014, and accepted.6 Multiple trials used these criteria, permitting comparison of response and tolerability.7-10 However, recent trials included differing atypical BOS definitions (see table).1,11-13 Because 33% of this cohort lack National Institutes of Health-BOS, it is unclear how to interpret the aggregate 34.7% response rate.1
These results diverge from the prior ruxolitinib study showing an 8.6% response in BOS,2 although pulmonary function tests were not captured, relying upon the Lee Symptom Scale metric. However, other studies have shown concordance between these tests.1,7,8,11,12 It is thus possible that atypical BOS patients inflated the response, possibly reflecting responses to restrictive lung GVHD.3,14-16 Alternatively, atypical BOS patients could obscure a higher response, diluting the cohort with poorly responsive myositis, myalgia, or infections.2
A control group could mitigate these factors, as shown in 1 study.13 Established patients are more likely to skew the results toward stability, with 27% exhibiting prolonged stable disease.1 In addition, cotreatment with other BOS-directed therapies at diagnostic onset complicates response assessments in this study, affecting the majority of patients.8,13
We request details regarding the atypical-BOS pulmonary function test response in this trial. Although it may be time to use data to refine the National Institutes of Health’s definition of BOS, we plead with our community to report the number and details of non-BOS lung cGVHD separately to enhance our understanding of responses, pathogenesis, and phenotypes.17
Acknowledgment: Funding for this study was provided in part by the National Institutes of Health, National Heart, Lung, and Blood Institute grant R01HL162661.
Contribution: K.M.W. wrote and designed the manuscript; and V.L., K.R.C., K.M.W., and G.A.Y. edited the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Kirsten M. Williams, Department of Pediatrics, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Emory University, 1760 Haygood Drive, 4th floor W468, Atlanta, GA 30322; email: Kwill99@emory.edu.
