JOURNAL ARTICLE
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Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden.

Allogeneic stem cell transplantation is the only known curative therapy for myelodysplastic syndromes (MDS). We present the transplant outcomes for 84 adult MDS patients, median age 50 (18-69 years), undergoing allogeneic hematopoietic stem cell transplantation (HSCT) at the University of Minnesota between 1995 and 2007. By WHO criteria 35 (42%) had refractory anemia with excess blasts (RAEB-1 or 2), 23 (27%) had refractory cytopenia with multilineage dysplasia (RCMD) or RCMD and ringed sideroblasts (RCMD-RS), and the remaining 26 (31%) had refractory anemia (RA), myelodysplastic syndrome-unclassifiable (MDS-U), chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative disease (MDS/MPD), or myelodysplastic syndrome-not otherwise specified (MDS-NOS). Graft source was related in 47 (56%), unrelated donor (URD) marrow in 11 (13%), and unrelated cord blood (UCB) in 26 (31%). The conditioning regimen included total body irradiation (TBI) in 94% of transplantations; 52 (62%) myeloablative (MA) and 32 (38%) nonmyeloablative (NMA) regimens. Cumulative incidence of neutrophil engraftment by day +42, acute graft-versus-host disease (aGVHD) by day +100, and chronic GVHD (cGVHD) by 1 year were 88% (80%-96%, 95% confidence interval [CI]), 43% (36%-50%, 95% CI), and 15% (10%-20%, 95% CI), respectively. One-year treatment-related mortality (TRM), relapse, disease-free survival (DFS), and overall survival (OS) were 39% (28%-50%, 95% CI), 23% (12%-32%, 95% CI), 38% (28%-48%, 95% CI), and 48% (38%-58%, 95% CI) respectively. Cumulative incidence of relapse at 1 year in patients with pre-HCT complete remission (CR) or <5% blasts was improved at 18% (8%-28%, 95% CI) compared to 35% (16%-54%, 95% CI) in patients with 5%-20% blasts (P = .07). Additionally, with MA conditioning, the incidence of relapse at 1 year trended lower at 16% (6%-26%, 95% CI) versus 35% (18%-52%, 95% CI) in NMA (P = .06), and a statistically significant decrease in relapse was noted in patients entering HCT with CR or <5% blasts with an incidence of 9% (0%-18%, 95% CI) (MA) versus 31% (11%-51%, 95% CI) (NMA) (P = 0.04). For those patients with > or =5% blasts, MA conditioning did not significantly decrease relapse rates. One-year TRM was similar between MA and NMA conditioning. For patients entering transplant in CR or with <5% blasts, prior treatment to reach this level did not impact rates of relapse or transplant-related mortality when all patients were analyzed; however, when broken down by conditioning intensity, there was a trend toward improved DFS in those NMA patients who were pretreated. Finally, 1-year DFS was similar using related donor peripheral blood stem cell (PBSC)/marrow, URD marrow, or UCB grafts. These data suggest that (1) blast percentage <5% at HSCT is the major predictor of improved DFS and relapse and prior treatment to reach this disease status may have value in leading to improved DFS; (2) MA conditioning is associated with lower relapse risk, particularly in patients with CR or <5% blasts, but is not able to overcome increased disease burden; (3) NMA conditioning yields equivalent TRM, DFS, and OS, and is reasonable in patients unsuited for MA conditioning; (4) the donor sources tested (PBSC, bone marrow [BM], or UCB) yielded similar outcomes.

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