Diffuse alveolar hemorrhage after hematopoietic cell transplantation- response to treatments and risk factors for mortality

• Type of Material: Article
• Authors: Michelle L Schoettler, Emory University; Christopher E Dandoy, University of Cincinnati; Anora Harris, Emory University; Marilynn Chan, University of California San Francisco; Keiko M Tarquinio, Emory University; Sonata Jodele, University of Cincinnati; Muna Qayed, Emory University; Benjamin Watkins, Emory University; Pradip Kamat, Emory University; Toni Petrillo, Emory University; Jeremy Obordo, Emory University; Christine S Higham, University of California San Francisco; Christopher C Dvorak, University of California San Francisco; Adrianna Westbrook, Emory University; Matt S Zinter, University of California San Francisco; Kirsten M Williams, Emory University
• Language: English
• Date: 2023-07-20
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Schoettler, Dandoy, Harris, Chan, Tarquinio, Jodele, Qayed, Watkins, Kamat, Petrillo, Obordo, Higham, Dvorak, Westbrook, Zinter and Williams
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2023.1232621
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 13
• Start Page: 1232621
• End Page: 1232621
• Grant/Funding Information: MS-NIH NCI K2CA237806-04), PeRSERVERE funding, and MZ NHLBI K23HL146936
• Keywords: inhaled tranexamic acid (INH TXA); transplant-associated thrombotic microangiopathy (TA-TMA); diffuse alveolar hemorrhage (DAH); TRANEXAMIC ACID; CORTICOSTEROID-THERAPY; sinusoidal obstructive syndrome (SOS); inhaled recombinant activated factor VIIa (INH fVIIa); Oncology; non-relapse related mortality; steroids; Science & Technology; RECOMBINANT FACTOR VIIA; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Biology, Biostatistics; Health Sciences, Immunology

Abstract

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of hematopoietic cellular therapy (HCT). This study aimed to evaluate the effect of DAH treatments on outcomes using data from consecutive HCT patients clinically diagnosed with DAH from 3 institutions between January 2018-August 2022. Endpoints included sustained complete response (sCR) defined as bleeding cessation without recurrent bleeding, and non-relapse mortality (NRM). Forty children developed DAH at a median of 56.5 days post-HCT (range 1-760). Thirty-five (88%) had at least one concurrent endothelial disorder, including transplant-associated thrombotic microangiopathy (n=30), sinusoidal obstructive syndrome (n=19), or acute graft versus host disease (n=10). Fifty percent had a concurrent pulmonary infection at the time of DAH. Common treatments included steroids (n=17, 25% sCR), inhaled tranexamic acid (INH TXA,n=26, 48% sCR), and inhaled recombinant activated factor VII (INH fVIIa, n=10, 73% sCR). NRM was 56% 100 days after first pulmonary bleed and 70% at 1 year. Steroid treatment was associated with increased risk of NRM (HR 2.25 95% CI 1.07-4.71, p=0.03), while treatment with INH TXA (HR 0.43, 95% CI 0.19- 0.96, p=0.04) and INH fVIIa (HR 0.22, 95% CI 0.07-0.62, p=0.005) were associated with decreased risk of NRM. Prospective studies are warranted to validate these findings.