Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with MDS. However, the advanced age of the majority of patients with MDS poses a significant barrier to the success of transplantation. Many of these patients have co-morbidities, or lack a suitable sibling matched donor. While reduced intensity conditioning (RIC) has expanded the scope of allografting to older patients, it remains unclear as to whether it confers an improvement in overall survival in this patient sub-group. Here we report on the results of a retrospective multi-centre analysis of 1385 patients aged 50 years or older with MDS transplanted since 1993. The main variables analysed in this study were donor status (sibling vs unrelated matched), age group (50–60 years vs >60years), disease stage at time of transplantation (early:<5% blasts vs advanced:>5% blasts), type of conditioning regimen (RIC vs standard myeloablative conditioning, SMC), period of transplantation (1993–96, 1997–2000–2001-).
There were 1000 matched sibling (72%) and 385 matched unrelated donor transplants (28%). The median age of the cohort was 56 years (range:50–74 years), with 1053 patients (76%) aged 50–60 years and 332 patients (24%) above 60 years. 604 patients(44%) received SMC and 781 patients (56%) received RIC. 189 patients (14%) had RA/RARS, 388 patients (28%) had RAEB, 233 patients(17%) had RAEB-t and 393 patients secondary AML (28%). FAB classification was unavailable for 182 patients (13%). Patients receiving RIC were older (age>60 years: 30% RIC vs 14% SMC, p<0.001), but SMC had a more advanced disease stage at transplant (42% RIC vs 51% SMC). There was no difference in donor type between RIC and SMC (MUD: 28% RIC vs 28% SMC)
The estimated cumulative incidence (competing risk model) at 4-years post transplant for TRM decreased from 47%(1993–1996), via 40%(1997–2000) to 35%(2001-); for Relapse Incidence these figures are 29%, 33% and 40% respectively. On multivariate analysis, age >60 years(HR:1.28, 95%CI [1.0–1.6], p=0.04), use of RIC (HR:1.50 95%CI [1.2–1.9], p<0.001) and advanced disease stage at transplantation (HR:1.51, 95%CI [1.2–2.0], p=0.002) were associated with an increased relapse rate; the use of RIC with a lower TRM (HR:0.71, 95%CI [0.57–0.88], p<0.01) and advanced disease stage at transplantation with a higher TRM (HR: 1.4, 95%CI [1.1–1.8], p<0.01) In contrast, donor type did not significantly influence either the 4-year TRM or relapse rates(HR’s 1.12 and 0.94 respectively, both p>0.30). Advanced disease stage at transplantation was the only independent variable associated with an inferior 4-year overall survival(OS)(HR: 1.47, 95%CI [1.2–1.8], p<0.001).
In conclusion, disease stage at time of transplantation has an important prognostic impact on outcomes. The use of RIC is associated with higher relapse but lower TRM and comparable OS with SMC in this cohort. While patients aged >60 years had an increased relapse rate, there was no significant difference in OS compared with those aged 50–60 years. The choice of donor did not significantly influence outcomes. Long-term survival can be achieved in a sub-group of older MDS patients, but prospective studies are warranted to improve patient selection and to identify optimal treatment strategies.
Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha
