Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes

Abstract

In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)-identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P ‫؍‬ .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC group (HR, 0.61; 95% CI, 0.41-0.91; P ‫؍‬ .015). The 3-year probabilities of progression-free and overall survivals were similar in both groups (39% after SMC vs 33% in RIC; multivariate P ‫؍‬ .9; and 45% vs 41%, respectively; P ‫؍‬ .8). In conclusion, the lower 3-year NRM after RIC is encouraging, since these patients were older (age > 50 years in 73% RIC vs 28% in SMC, P < .001) and had more adverse pretransplantation variables. However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS. (Blood. 2006;108:836-846)

Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year‐old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT)

“…In this setting, the efficacy of SCT relies essentially on a potent GvL. Most retrospective studies have shown similar outcomes between RIC/NMA and conventional myeloablative conditioning (MAC), but with more relapse with RIC and NMA, and more toxicity with the conventional approach [16,17]. However, AML appears to be less sensitive to the GvL than other diseases such as chronic myelogenous leukemia [18], and some degree of dose intensity has been shown as important in the outcome of AML [19].…”

Allogeneic hematopoietic stem cell transplantation (HSCT) after reduced intensity conditioning

“…Obviously these studies are limited by the fact that fitter patients were probably more often proposed myeloablative regimens, while older and sicker patients were given nonmyeloablative or RIC regimens. Nevertheless, these studies found similar disease-free and overall survivals in the two groups of patients, since non-relapse mortality was lower in nonmyeloablative patients, but relapse rates were lower in myeloablative recipients [23][24][25].…”

“…Three large retrospective studies from the EBMT have compared HSCT outcomes of patients given various myeloablative versus various RIC/nonmyeloablative regimens as treatment for AML, MDS, or chronic lymphocytic leukemia (CLL) ( Table 1) [23][24][25]. Obviously these studies are limited by the fact that fitter patients were probably more often proposed myeloablative regimens, while older and sicker patients were given nonmyeloablative or RIC regimens.…”

“…Martino et al reported the outcomes of 215 patients given one of various RIC or nonmyeloablative conditioning regimens as treatment for MDS (refractory anemia (n = 20) or more advanced MDS (n = 195)) in EBMT-affiliated centers [25]. Three-year incidences of relapse and non-relapse mortality were 45% and 22%, respectively, while 3-year overall survival was 41%.…”

Hematopoietic cell transplantation for patients with myelodysplastic syndromes (MDS): When, how and for whom?

“…39 A report by Martino et al on results in 621 patients conditioned with high-dose and 215 patients prepared with reducedintensity conditioning (RIC) regimens (including patients in all MDS categories) showed a significantly higher 3-year relapse rate (HR 1.64; p=0.001) but a significantly lower NRM (HR 0.61; p=0.015) in RIC patients. 40 As a result, 3-year RFS was comparable, 39% and 33% for high dose and RIC, respectively (Figure 1). It is important to note that RIC patients were older (73% versus 28% >50 years; p< 0.001) and had more adverse pre-HCT conditions, a pattern also present in other studies.…”