Peritransplantation Red Blood Cell Transfusion Is Associated with Increased Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day -7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.

RBC and platelet transfusion support in the first 30 and 100 days after haploidentical hematopoietic stem cell transplantation

“…A previous study showed that peritransplantation RBC transfusions were associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggested that reducing RBC transfusion may reduce the incidence of severe GVHD. 45 However, we could not demonstrate that increased transfusions led to the development of GVHD (See Figure S1, available as supporting information in the online version of this paper). Our analysis showed no association between higher than median RBC and platelet transfusion requirements in the first 30 days and subsequent diagnosis of significant (Grade II or higher) aGVHD between Days 31 and 100.…”

Is anemia a harbinger of poorer outcomes after allogeneic hematopoietic cell transplant?

“…Red blood cell transfusions are not without risks; there are risks of transfusion-related acute lung injury [6], transfusion-associated circulatory overload [6], transfusion reactions [6], infectious disease risk [6], iron overload [7], idiopathic pneumonia syndrome [8], increased graft versus host disease [9], and economic burdens [10]. Several of the transfusion risks, transfusion-associated acute lung injury, transfusion-associated circulatory overload, transfusion reactions, and infection risk are not unique to transplant, but are associated with transfusions in general [6].…”

“…Additionally, red blood cell transfusions may be associated with an increased risk of idiopathic pneumonia syndrome after allogeneic hematopoietic cell transplant [8]. Increased numbers of blood transfusions are associated with increased risk of severe acute graft versus host disease and decreased overall survival after allogeneic hematopoietic cell transplant [9]. In contrast to the findings of Hosoba and colleagues [9], the authors did not find an association between number of red blood cell units transfused and acute or chronic graft versus host disease in a single-unit umbilical cord blood transplant [1].…”

“…Increased numbers of blood transfusions are associated with increased risk of severe acute graft versus host disease and decreased overall survival after allogeneic hematopoietic cell transplant [9]. In contrast to the findings of Hosoba and colleagues [9], the authors did not find an association between number of red blood cell units transfused and acute or chronic graft versus host disease in a single-unit umbilical cord blood transplant [1]. This difference in outcomes could be related to decreased graft versus host disease seen in cord blood transplant recipients.…”

“…When the number of red blood cell units transfused are reduced, there is a reduction in transfusion-related risks [6][7][8][9] and a significant cost savings [10]. Two potential strategies may reduce the usage of red blood cell transfusions in allogeneic hematopoietic cell transplants, reduce the number of transfusions using a restrictive transfusion policy [13] or prevent the hemoglobin from dropping below a defined level using erythropoietic stimulating agents [14].…”