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Risk factors and outcomes of diffuse alveolar haemorrhage after allogeneic haematopoietic stem cell transplantation
Wu, J., Fu, H. X., He, Y., Mo, X. D., Liu, X., Cai, X., Gui, R. Y., Liu, H. X., Yan, C. H., Chen, Y. H., et al
Bone marrow transplantation. 2021;:1-11
Abstract
Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P?=?0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P?0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P?0.001), and a high D-dimer level (>500?ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.
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Management of Diffuse Alveolar Hemorrhage in the Hematopoietic Stem Cell Transplantation Population: A Systematic Review
Loecher, A. M., West, K., Quinn, T. D., Defayette, A. A.
Pharmacotherapy. 2021
Abstract
Pulmonary complications post hematopoietic stem cell transplantation (HSCT) such as diffuse alveolar hemorrhage (DAH) can occur in 2% to 14% of HSCT patients and has a mortality greater than 80%. Diffuse alveolar hemorrhage is considered to be an inflammatory response therefore HSCT patients are primarily treated with different types of systemic corticosteroids with varying dosages. Other treatments currently reported in the literature in conjunction with corticosteroids include aminocaproic acid, recombinant factor VIIa (rFVIIa), and etanercept. This review highlights appropriate frontline and adjunctive treatment options for HSCT patients with DAH and outcomes for each intervention. To perform the review, the PubMed database was searched from inception through March 19, 2021, to identify potential studies using the search terms DAH and HSCT, DAH and hematopoietic cell transplant (HCT), DAH and stem cell, lung injury and HSCT, and lung injury and HCT. When applicable, references from articles identified in the search were also reviewed for inclusion. Much of the data identified was limited to retrospective cohort studies and case-series. Based on the data available, the treatment approach should consist of corticosteroid therapy with a suggested methylprednisolone dose of 250 milligrams daily followed by a 50% taper every 3 days. Intra-pulmonary administration of rFVIIa and intravenous administration of aminocaproic acid could be considered as adjunctive agents in those patients who do not promptly respond to corticosteroid therapy. Due to a lack of data specific to HSCT patients who develop DAH and the risk of infectious complications, etanercept should be avoided. Future studies should be designed as randomized controlled trials and examine the use of adjunctive therapies in the upfront setting for HSCT patients with DAH.
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3.
Epidemiology, Risk Factors and Outcomes of Diffuse Alveolar Hemorrhage after Hematopoietic Stem Cell Transplantation
Zhang, Z., Wang, C., Peters, S. G., Hogan, W. J., Hashmi, S. K., Litzow, M. R., Patnaik, M. S., Niven, A. S., Yadav, H.
Chest. 2021
Abstract
BACKGROUND Diffuse alveolar hemorrhage (DAH) is an uncommon complication of hematopoietic stem cell transplant (HCT) that carries high morbidity and mortality. There are limited contemporary data regarding the incidence, outcomes and risk factors for DAH. RESEARCH QUESTION What are the incidence, outcomes, and risk factors for developing DAH after HCT? METHODS This is a single-center retrospective cohort study of patients who underwent HCT between January 1, 2005 and December 31st, 2016. The incidence and outcomes of DAH development were evaluated. A multivariable logical regression model was used to analyze differences between survivors and non-survivors. RESULTS Of 4350 patients undergoing first-time HCT, DAH was diagnosed in 99 (2.3%). DAH was seen in 40 of 3536 autologous HCT recipients (1.1 %) and 59 of 814 allogeneic HCT recipients (7.2 %). Mean age was 53 ± 13 years and median time of DAH diagnosis was 126 days (interquartile range: 19-349) post-HCT. In-hospital mortality and mortality one year after DAH diagnosis were 55.6% and 76.8% respectively. DAH diagnosis more than 30 days after transplant (OR: 7.06, 95% CI: 1.65-30.14), low platelet count (OR: 0.98, 95% CI: 0.96-1.0, p = 0.02), elevated INR (OR: 4.08, 95% CI: 0.64-25.88, p = 0.046) and need for invasive mechanical ventilation (OR: 8.18, 95% CI: 1.9-35.21) were associated with higher in-hospital mortality. Steroid treatment did not alter mortality (p= 0.80) or length of stay (p= 0.65). However, among those who received steroids, survival was higher in whose who received modest-dose (<250mg methylprednisolone equivalent/day) compared to those who received high dose (=250mg methylprednisolone equivalent/day) steroids (OR: 0.21, 95% CI: 0.07-0.72). INTERPRETATION The mortality of DAH after HCT remains high, and patients can develop DAH long after transplantation. Later development of DAH (>30 days after HCT), need for invasive mechanical ventilation, thrombocytopenia and elevated INR are all associated with worse outcomes.
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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.