Allogeneic SCT with Matched Related and Unrelated Donors for Patients (pts) with Refractory Anemia (RA): Improved Survival after Introduction of Reduced Intensity Conditioning (RIC) Regimens.

Early alloSCT of pts with MDS before transformation usually results in a 50% EFS, but the nonrelapse mortality (NRM) has precluded a general application of alloSCT for patients with RA. Introduction of RIC has allowed the application of alloSCT to more advanced ages. This study evaluated the impact of recipient age, transplant year, interval between diagnosis and SCT (Dx-SCT), cytogenetic characteristics, T-cell depletion (TCD), type of donor, and the intensity of the conditioning regimen on the outcome of alloSCT. The study population consisted of 374 pts, 244 of whom have received a transplant from an HLA-id. sibling. None of the pts had progressed to advanced stages of MDS. 83 Pts received TCD grafts and 102 pts received SCT after RIC. 58 Pts were <20 yrs, 52 between 20-30, 66 between 30-40, 95 from 40-50 and 103 pts >50 yrs. 86 Pts received SCT before 1996, 125 in 1997-2001, and 163 pts more recently. 184 Pts have been transplanted with a Dx-SCT of <12 months, and 190 >12 months. Cytogenetic data were available for 197 pts, 85 of whom had cytogenetic abnormalities. The overall 5-year survival was 50% (SE: 3%). Relapse occurred in 44% pts resulting in a 5-year relapse risk of 21% (SE: 3%). NRM was the cause of failure in 120 pts resulting in a 5-year NRM of 41% (SE: 3%). The survival after SCT with matched related and unrelated donors was 54% and 48% resp. Young age was associated with better survival in the univariate model (p=0.04). An association exists between various factors such as between age and regimen type, transplantation year, or donor type. Therefore the outcome of the multivariable analyses was based on Cox models with age, transplant year, type of donor, Dx-SCT, stem cell source, and regimen type as main factors. Variables with a significant impact on survival were transplant year with an improved survival in more recently performed SCT (HR=0.95/year; p=0.05), TCD (HR=1.5; p=0.03) and Dx-SCT >12 months (HR=1.4; p=0.05) while higher age (HR=1.1/10 years; p=0.08) and RIC (HR=1.0; p=1.0) did not influence outcome significantly. The HR of RIC for relapse-free survival was 1.2; p=0.5. The fully adjusted estimate for relapse after RIC was HR=4.1 (p=0.002). The NRM was lower after RIC: HR 0.7 (P=0.22), but this difference was not significant. The donor type and the source of stem cells did not influence significantly any of the outcome variables. This data show that alloSCT results in excellent outcome nowadays, even at older age and using matched unrelated donors. The relatively high relapse rate observed after RIC warrants prospective studies.