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Stem Cell Transplantation
Diffuse alveolar hemorrhage is most
often fatal and is affected by graft source, conditioning regimen toxicity,
and engraftment kinetics
Fatma Keklik,1 Ezzideen Barjes Alrawi,1 Qing Cao,2 Nelli Bejanyan,1 Armin Rashidi,1 Aleksandr Lazaryan,1 Patrick Arndt,3 Erhan H. Dincer,3 Veronika Bachanova,1 Erica D. Warlick,1 Margaret L. MacMillan,4 Mukta Arora,1 Jeffrey Miller,1 Claudio G Brunstein,1 Daniel J. Weisdorf1 and Celalettin Ustun1
1Division of Hematology-Oncology and Transplantation, Department of Medicine; 2Biostatistics and Bioinformatics; 3Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine and 4Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
ABSTRACT
Diffuse alveolar hemorrhage after hematopoietic stem cell trans- plantation is a frequently fatal complication with no standard therapy. Although significant changes in supportive and inten- sive care measures for patients undergoing hematopoietic stem cell transplantation 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 inci- dence, risk factors, and outcomes of diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage developed in 5% of allogeneic hematopoi- etic stem cell transplant recipients, at a median of 30 days (range +3 to +168 days) after transplantation. The incidence of diffuse alveolar hem- orrhage was significantly greater in recipients of umbilical cord blood than peripheral blood or bone 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 following peripheral blood or bone marrow hematopoietic stem cell transplants (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 transplant recipients (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 bone marrow and umbilical cord blood hematopoietic stem cell transplants (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 hemor- rhage is multifactorial, involving lung injury influenced by high-dose total body irradiation, graft source, and delayed engraftment or graft fail- ure. The survival of patients with diffuse alveolar hemorrhage after hematopoietic stem cell transplantation remains poor. Clinical interven- tions or experimental studies (e.g., cell expansion for umbilical cord blood transplants or thrombopoietin use) that modulate these risk fac- tors may limit the incidence and improve the outcomes of diffuse alve- olar hemorrhage.
Ferrata Storti Foundation
Haematologica 2018 Volume 103(12):2109-2115
Correspondence:
celalettin_ustun@rush.edu
Received: January 23, 2018. Accepted: July 27, 2018. Pre-published: August 3, 2018.
doi:10.3324/haematol.2018.189134
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/12/2109
©2018 Ferrata Storti Foundation
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haematologica | 2018; 103(12)
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