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

Michelle L Schoettler; Christopher E Dandoy; Anora Harris; Marilynn Chan; Keiko M Tarquinio; Sonata Jodele; Muna Qayed; Benjamin Watkins; Pradip Kamat; Toni Petrillo; Jeremy Obordo; Christine S Higham; Christopher C Dvorak; Adrianna Westbrook; Matt S Zinter; Kirsten M Williams

doi:10.3389/fonc.2023.1232621

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

Front Oncol. 2023 Jul 20:13:1232621. doi: 10.3389/fonc.2023.1232621. eCollection 2023.

Authors

Michelle L Schoettler¹, Christopher E Dandoy², Anora Harris¹, Marilynn Chan³, Keiko M Tarquinio⁴, Sonata Jodele², Muna Qayed¹, Benjamin Watkins¹, Pradip Kamat⁴, Toni Petrillo⁴, Jeremy Obordo¹, Christine S Higham⁵, Christopher C Dvorak⁵, Adrianna Westbrook⁶, Matt S Zinter^{5

7}, Kirsten M Williams¹

Affiliations

¹ Division of Blood and Marrow Transplantation, Children's Healthcare of Atlanta, Aflac Blood and Cancer Disorders Center, Emory University, Atlanta, GA, United States.
² Cincinnati Children's Medical Center, Division of Bone Marrow Transplantation and Immune Deficiency, University of Cincinnati School of Medicine, Cincinnati, OH, United States.
³ Pediatric Pulmonary Medicine, University of California, San Francisco, San Francisco, CA, United States.
⁴ Division of Critical Care Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, United States.
⁵ Pediatric Allergy, Immunology, and Bone Marrow Transplant Division, University of California, San Francisco, San Francisco, CA, United States.
⁶ Department of Pediatrics, Pediatric Biostatistics Core, Emory University, Atlanta, GA, United States.
⁷ Pediatric Critical Care, University of California, San Francisco, San Francisco, CA, United States.

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.

Keywords: diffuse alveolar hemorrhage (DAH); inhaled recombinant activated factor VIIa (INH fVIIa); inhaled tranexamic acid (INH TXA); non-relapse related mortality; sinusoidal obstructive syndrome (SOS); steroids; transplant-associated thrombotic microangiopathy (TA-TMA).