Recent improvement in outcome of unrelated donor transplantation for aplastic anemia

Abstract

The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 3278% before 1998 to 5778% after 1998 (Po0.0001). When comparing the cohort before (n ¼ 149) and after 1998 (n ¼ 349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, Po0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P ¼ 0.02) and less chronic GvHD (22 vs 38%, P ¼ 0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.

Decision-Making and Problem Solving

“…10,15,23,26 DNA-based HLA-typing was performed for all participants in 5 published studies, 16,20,28,29,31 and for the majority of participants in 5 other studies. 15 10,17,20,21,23,25,[27][28][29][30][31][32] Reactivation of disease caused by cytomegalovirus and Epstein-Barr virus was observed in 3 studies. 23,31,32 In the controlled trial, 205 children and young people under 18 years of age with SAA were enrolled, 26 of whom 198 were treated with IST.…”

“…A median of 32 patients (range 11-349, total 1,645) were investigated in the total study population of 14 studies 11,[15][16][17][21][22][23][25][26][27][28][29]31,32 and in 8 relevant subgroups of 4 other studies. 10,20,24,30 The patients' median age in the individual studies was between eight and 27 years and the ratio of males : females ranged from a male (30 : 10) to a female preponderance (11 : 20). Most of the 1,645 patients whose data were used for survival estimates had received a pre-transplantation IST to which they had not responded or after which they had relapsed.…”

“…In one study, 10 4 different donor types were investigated in subgroups according to the HLA status, although, only the 2 subgroups with HLA-matched unrelated donors versus HLA-mismatched unrelated donors were included in the present report. The year of transplant was investigated in subgroups in another study: 30 before versus after and in 1998.…”

“…15,16,20,24 A consecutive enrolment was stated in 3 23,25,27 of 13 retrospective case series. 10,11,17,[21][22][23]25,[27][28][29][30][31][32] Transplantations were performed between 1981 and 2006.…”

Role of HLA in hematopoietic SCT

“…12 After 1998, when better HLA typing methods replaced DNA fingerprinting, serology and low-resolution methods used for final donor matching the overall survival (OS) of transplant patients has improved greatly. 13 However, better transplant procedures and effective rescue of patients relapsing after HSCT might favorably influence the transplant outcome as well. 14 In contrast, OS, EFS, transplantation-related mortality, relapse and high-grade acute GVHD rates after HSCT from precisely typed perfectly matched UDs reach levels comparable to the classical MR donors.…”