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Haematopoietic cell transplantation also recommended in older patients with advanced high-risk myelodysplastic syndrome with a suitable donor

To date, haematopoietic cell transplantations (HCT) are rarely performed for older patients with high-risk myelodysplastic syndrome (MDS). Results of a trial from the Blood and Marrow Transplant Clinical Trials Network, presented at ASH 2020, may change this picture. In fact, this study demonstrated a significant overall survival advantage in older patients (50-75 years) with intermediate-2 and high-risk de novo MDS and a matched-HLA donor who underwent reduced-intensity conditioning followed by an HCT. Importantly, this benefit was observed regardless of the age group (below or above 65 years). As such, these data underscore that HCT should be included as an integral part of MDS management plans for patients with higher-risk MDS, irrespective of age.


To date, an allogeneic haematopoietic cell transplantation (HCT) remains the only curative treatment option for patients with MDS. Although HCT is widely used in younger MDS patients, early transplantation of older patients is infrequently offered due to a lack of well-defined risk-benefits of HCT over non-HCT therapy in this patient population. Nevertheless, retrospective studies suggest that transplantation outcomes among selected older patients with MDS are similar to what is obtained in younger patients. To evaluate this in a prospective manner, a multi-centre biologic assignment trial comparing reduced intensity allogeneic HCT to hypomethylating therapy or best supportive care in patients aged 50-75 with advanced MDS was performed. Assignment to the Donor or No Donor arm was based on HLA-typing of eligible family members and a 90-day search of unrelated donor registries. Subjects were initially assigned to the No Donor arm and re-assigned to the Donor arm when a suitable donor was identified. Those patients for whom the donor search ended without a suitable donor or those who died within that period remained in the No Donor arm. All eligible patients were between 50 and 75 years old with de novo intermediate-2 or high-risk MDS at any point in their disease history and were expected to undergo reduced-intensity transplantation within six months of enrolment. Prior or ongoing hypomethylating therapy was allowed, but no prior donor search was permitted. The primary endpoint of the study was the adjusted three-year overall survival (OS).


Out of the 384 enrolled patients, a donor could be identified for 260 patients. For patients for whom no donor could be identified, seven patients died during the 90-day search. Patient and disease characteristics were well-balanced between both groups. In an intention-to-treat analysis, the adjusted OS at three years from study enrolment in the Donor arm was 47.9% as compared to 26.6% in the No Donor arm, representing a statistically significant absolute difference of 21.3% (p=0.0001). Of note, a sensitivity analysis excluding patients assigned to the No Donor arm who died or withdrew prior to the end of the 90-day search window, did not lead to a different outcome (adjusted OS: 48.0% vs. 28.1%, p=0.0004). Also the leukaemia-free survival (LFS) at three years was higher in the Donor arm compared with the No Donor arm (35.8% vs. 20.6%, p=0.003). Both the OS and LFS benefit were observed across all subgroups tested, including patients above or below age 65. Main reasons for non-compliance included the use of myeloablative conditioning or failure to proceed to RIC transplant in the Donor arm, and the use of alternative donors in the No Donor arm, and resulted in an overall non-compliance rate of 26.3%. Therefore, also an as-treated analysis of OS and LFS was performed. For both three-year OS (47.4% vs. 16.0%, p<0.0001) and LFS (39.3% vs. 10.9%, p<0.0001) as-treated analyses suggest a strong advantage for HCT versus non-HCT therapy. Quality of life (QoL) measurements were performed by means of the FACT-G, the MOS-SF36 Physical and Mental Component Scores and the EQ-5D utility score. No clinically significant differences in QoL at any time point were reported.


Among higher-risk MDS patients aged 50-75, having a suitable donor leads to improved outcomes, with subjects older than 65 years having similar outcomes to those below 65 years. In addition, no decrease in QoL compared to No Donor controls was observed. As such, HCT should be included as an integral part of MDS management plans for patients with higher-risk disease.


Nakamura R, Saber W, Martens MJ, et al. Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102. Presented at ASH 2020; Abstract 75.

Speaker Corey Cutler

Corey Cutler

Corey Cutler, MD, MPH, FRCPC, Division of Stem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, MA, USA


See: Keyslides


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