Improved Survival after Allogeneic Hematopoietic Stem Cell Transplantation in Recent Years. A Single-Center Study

Abstract

We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.

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

“…These results are compatible with prior reports. [1][2][3][4][5][6][7] There were remarkable changes in patient background characteristics over the three periods, such as an increased number of cases of HSCT from a UBM donor, older patients and patients with high-risk disease. Despite the extended application of HSCT to these more vulnerable patients, there was an improvement in outcome after HSCT.…”

“…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.…”

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.…”

“…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.…”

“…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.…”