Improved survival after acute graft- versus -host disease diagnosis in the modern era

Abstract

A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft-versus-host disease (n=497 for 1999–2001, n=962 for 2002–2005, n=1,446 for 2006–2010). The median (range) follow-up was 144 (4–174), 97 (4–147) and 60 (8–99) months for 1999–2001, 2002–2005, and 2006–2010, respectively. Among the cohort with grade II-IV acute graft-versus-host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999–2001, 2002–2005, and 2006–2012, respectively (P<0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease.

Clinical Outcomes and Healthcare Resource Utilization for Gastrointestinal Acute Graft-versus-Host Disease after Allogeneic Transplantation for Hematologic Malignancy: A Retrospective US Administrative Claims Database Analysis

“…The proportion of patients who did not develop aGVHD among the total group of 1215 patients remained steady across the study period, and their survival improved significantly, by 66%, consistent with improvement in supportive care measures for transplant recipients. In contrast to our findings, Khoury et al [30] examined outcomes following a diagnosis of grade II-IV aGVHD by time period and explored effects according to original prophylactic regimen and grade. There was a decrease in the proportion of grade III-IV aGVHD over time (from 56% for 1999 to 2001 to 47% for 2002 to 2005 and 37% for 2006 to 2012), which is reflective of the longer time period analyzed compared with our study which is a more contemporary analysis.…”

“…In this study, among allo-HCT recipients with a hematologic malignancy who were discharged alive from the hospital, the survival rate was 72.7% in those who developed GI aGVHD, compared with 80.4% in those who did not develop aGVHD. This finding is consistent with a recent study using data from the Center for International Blood and Marrow Transplant Research that found a 40% to 70% 1-year survival rate in patients (N = 1446) who developed grade II-IV aGVHD treated between 2006 and 2012 [30].…”

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

“…Corticosteroids are the mainstay of treatment for acute GVHD, and the prognosis of steroid-refractory disease is poor [69,73]. Prophylaxis against GVHD is an essential part of allogeneic transplant regimens and includes a variety of modalities, including calcinuerin inhibitors, anti-metabolites, and post-transplant cyclophosphamide [74].…”

“…Prophylaxis against GVHD is an essential part of allogeneic transplant regimens and includes a variety of modalities, including calcinuerin inhibitors, anti-metabolites, and post-transplant cyclophosphamide [74]. As GVHD prophylaxis has improved, more patients are presenting with Grade II or Grade III acute GVHD (and fewer are presenting with Grade IV acute GVHD), the incidence of hepatic acute GVHD is decreasing, and overall mortality from acute GVHD is decreasing in patients treated with tacrolimusbased GVHD prophylaxis [73].…”

Better acute graft- versus -host disease outcomes for allogeneic transplant recipients in the modern era: a tacrolimus effect?

“…5 In a large registry analysis (n=2905) from the Center for International Blood and Marrow Transplant Research (CIBMTR), they evaluate the incidence and outcomes of grade II-IV acute GvHD developing within 100 days after myeloablative, HLA-matched HSCT over three successive time periods . These periods overlap with important advances in supportive care (e.g., azoles for fungal infections, valacyclovir for cytomegalovirus).…”