Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients

• Published in: Transplantation and cellular therapy 2024-10, Vol.30 (10), p.1017.e1-1017.e12
• Main Authors: Cheng, Geoffrey, Smith, Michael A., Phelan, Rachel, Brazauskas, Ruta, Strom, Joelle, Ahn, Kwang Woo, Hamilton, Betty, Peterson, Andrew, Savani, Bipin, Schoemans, Hélène, Schoettler, Michelle, Sorror, Mohamed, Higham, Christine, Kharbanda, Sandhya, Dvorak, Christopher C., Zinter, Matt S.
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; Comorbidities; Critical care; Diffuse alveolar hemorrhage; Female; Graft vs Host Disease - epidemiology; Graft vs Host Disease - etiology; Graft-versus-host disease; Hematopoietic Stem Cell Transplantation - adverse effects; Hemorrhage - epidemiology; Hemorrhage - etiology; Hemorrhage - mortality; Humans; Incidence; Infant; Lung Diseases - epidemiology; Lung Diseases - etiology; Male; Pulmonary Alveoli - injuries; Retrospective Studies; Risk Factors; Transplantation, Homologous - adverse effects; Transplantation-associated thrombotic microangiopathy; Young Adult
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2024.07.022

•Among 6995 HCT recipients, 81 (1%) developed DAH at a median of 54 days post-HCT.•DAH is rare but associated with mortality exceeding 70% by 1 year after diagnosis.•Risk increases with nonmalignant hematologic disease, CNI + MMF therapy, and acute GVHD.•Associated ICU comorbidities included hypertension, pericarditis, and renal failure. Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17%