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Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regiment toxicity, and engraftment kinetics
Keklik, F., Alrawi, E. B., Cao, Q., Bejanyan, N., Rashidi, A., Lazaryan, A., Arndt, P., Dincer, E. H., Bachanova, V., Warlick, E. D., et al
Haematologica. 2018
Abstract
Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation is a frequently fatal complication with no standard therapy. Although significant changes in supportive and intensive care measures for hematopoietic stem cell transplantation patients have been made over the past decades, the impact of these changes on the incidence and outcome of patients with diffuse alveolar hemorrhage has not been examined. We analyzed 1228 patients who underwent allogeneic hematopoietic stem cell transplantation between 2008-2015 at the University of Minnesota to study the incidence, risk factors, and outcomes of diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage developed in 5% of allogeneic hematopoietic stem cell transplantation recipients, a median day +30 (range +3 to +168 days) after hematopoietic stem cell transplantation. The incidence of diffuse alveolar hemorrhage was significantly greater in recipients of umbilical cord blood versus peripheral blood or marrow grafts (HR: 2.08, 95%CI: 1.16-3.74), p=0.01. In multivariate analysis, delayed neutrophil engraftment or primary graft failure was a risk factor for diffuse alveolar hemorrhage in peripheral blood or marrow hematopoietic stem cell transplantation (HR: 5.51, 95%CI: 1.26-24, p=0.02) and delayed platelet engraftment was associated with significantly increased diffuse alveolar hemorrhage in umbilical cord blood hematopoietic stem cell transplantation (HR: 6.96, 95%CI: 2.39-20-.29, p<0.05). Myeloablative regimens including total body irradiation were also risk factors for diffuse alveolar hemorrhage (HR: 1.8, 95%CI: 1.03-3.13, p=0.05), in both peripheral blood or marrow and umbilical cord blood hematopoietic stem cell transplantation (HR: 1.87, 95%CI:0.95-3.71). Patients with diffuse alveolar hemorrhage had an inferior 6-month treatment-related mortality (HR, 6.09 95%CI: 4.33-8.56, p<0.01) and 2-year overall survival (HR, 4.16 95%CI: 3.06-5.64, p<0.01) using either graft source. The etiology of diffuse alveolar hemorrhage is multifactorial involving lung injury influenced by high dose total body irradiation, graft source, and delayed engraftment or graft failure. The survival of patients with diffuse alveolar hemorrhage after hematopoietic stem cell transplantation remains poor. Clinical interventions or experimental studies (e.g., cell expansions in umbilical cord blood hematopoietic stem cell transplantation or thrombopoietin use) that modulate these risk factors may limit the incidence and improve the outcomes of diffuse alveolar hemorrhage.