Nonmyeloablative conditioning regimens

In view of the older age group of patients with a diagnosis of MDS and the inability of a significant proportion of these patients to receive a standard myeloabla-tive conditioning regimen, in the 1990s reduced intensity conditioning (RIC) or non-myeloablative conditioning regimens for an allogeneic SCT were actively pursued. It was hoped that this approach would reduce the RRT and NRM in this population. The most commonly used RIC regimen is a combination of fludarabine with either melphalan or low-dose TBI. Results from some of the largest series pub-lished27-32 are summarized in Table 42.3. In a majority of these studies, the NRM was lower with myeloabla-tive regimens but was associated with higher relapse rates, which was especially noted in the EBMT study.30 More recently a publication from the MD Anderson Cancer Center showed a similar correlation with an increased risk of relapse in the group receiving a less intensive conditioning regimen when comparing two

Table 42.2 Summary of data from some large series of patients with MDS who underwent a related matched, sibling allogeneic SCT using a myeloablative conditioning regimen

No. of Age High-Risk Preparative NRM (%) DFS (%) OS (%)

Study patients (median) MDS (%) regimen at 3 years

Sutton et al.14 71 37 100 TBI based 39 32 32

Appelbaum et al.7 251 38 (1-66) 57 TBI based, 69% 42 41 NS

de Witte et al.12 885 NS 52 NS 43 31 46

Sierra et al.13 452 38 (2-64) 60 TBI based, 40% 37 40 42

DFS - diseasefree survival; NRM - nonrelapse mortality; NS - not stated; OS - overall survival; TBI - total body irradiation.

reduced intensity regimens,31 suggesting that more intensive conditioning may be required. There are a number of ongoing clinical trials addressing this issue, and the optimal regimen remains to be defined.

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