Reducing the Risk for Transplantation-Related Mortality After Allogeneic Hematopoietic Cell Transplantation: How Much Progress Has Been Made?

Abstract

A B S T R A C T PurposeTransplantation-related mortality (TRM) is a major barrier to the success of allogeneic hematopoietic cell transplantation (HCT). Patients and MethodsWe assessed changes in the incidence of TRM and overall survival from 1985 through 2004 in 5,972 patients younger than age 50 years who received myeloablative conditioning and HCT for acute myeloid leukemia (AML) in first complete remission (CR1) or second complete remission (CR2). ResultsAmong HLA-matched sibling donor transplantation recipients, the relative risks (RRs) for TRM were 0.5 and 0.3 for 2000 to 2004 compared with those for 1985 to 1989 in patients in CR1 and CR2, respectively (P Ͻ .001). The RRs for all causes of mortality in the latter period were 0.73 (P ϭ .001) and 0.60 (P ϭ .005) for the CR1 and CR2 groups, respectively. Among unrelated donor transplantation recipients, the RRs for TRM were 0.73 (P ϭ .095) and 0.58 (P Ͻ .001) for 2000 to 2004 compared with those in 1990 to 1994 in the CR1 and CR2 groups, respectively. Reductions in mortality were observed in the CR2 group (RR, 0.74; P ϭ .03) but not in the CR1 group. ConclusionOur results suggest that innovations in transplantation care since the 1980s and 1990s have reduced the risk of TRM in patients undergoing allogeneic HCT for AML and that this reduction has been accompanied by improvements in overall survival. J Clin

Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation

“…Recently, several studies have shown improvements in outcomes of allo-HSCT over the past few decades, [1][2][3][4][5][6][7] explained mainly by the decreased risk of NRM.…”

“…A study by Horan et al 1 using the Center for International Blood and Marrow Transplant Research database showed a reduction in NRM in patients with AML in CR who received myeloablative HSCT. 1 An analysis from the European Group for Blood and Marrow Transplantation focused on causes of mortality after allo-HSCT from an HLA-identical sibling donor, and showed that death from infections was significantly reduced.…”

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

“…6 The HRs for NRM and overall mortality were lower in more recent time periods. Although several studies have shown changes in outcomes after allo-HCT, [1][2][3][4][5][6] this is the first analysis restricted to allo-HCT in nonremission, based on the patient age, donor source and disease type. The reduction in the HR for NRM was reflected in the reduced HR for overall mortality, and none of the subgroups showed a reduced risk for overall mortality without an improvement in NRM.…”

“…Despite the fact that high-risk acute leukemia is definitely indicated for allo-HCT, patients with non-remission leukemia carry various factors that lead to a higher risk of treatment-related toxicity, including comorbidities due to prior chemotherapy and intensified conditioning regimens in need of an antitumor effect, [7][8][9][10][11] and a deteriorated general condition due to refractory disease. Although prior studies have shown improvements in the outcome after allo-HCT, [1][2][3][4][5] little information is available on how changes in transplant modalities have affected the outcomes after allo-HCT in non-remission, based on patient age, donor source and disease type. We recently reported changes in the incidence and causes of NRM after allo-HCT in remission in Japan.…”

“…As a result, the risk of non-relapse mortality (NRM) after allo-HCT has decreased over the past few decades. [1][2][3][4][5][6] AML and ALL account for the largest proportion of diseases indicated for allo-HCT. Furthermore, a substantial number of patients with AML or ALL receive allo-HCT in non-remission.…”