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My Paper of the Month - Allogeneic hematopoietic stem cell transplantation (HSCT) in intermediate-2 and high risk myelodysplastic syndrome (MDS)


By Marie Robin, Haematology Department, Saint-Louis Hospital, APHP, Paris, France

Two papers testing the potential advantage of HSCT in higher risk elderly (> 50 years) MDS patients came out recently [1,2]. Several registry studies have previously reported that intermediate-2 and high risk (“higher risk”) International Prognostic Scoring System (IPSS) MDS patients can have a better life expectancy with transplantation[3–5]. In 2015, a French observational study comparing “no donor” and “donor” groups confirmed these results, with an advantage only observed after two years, possibly in relationship with the early transplant-related mortality superimposable to the disease-related mortality in non-transplanted patients [6].

Kröger et al. report the result of a prospective German multicentre phase II study comparing four cycles of 5-azacytidine (aza) followed by HSCT to a continuous therapy with 5-aza [2]. A total of 170 higher risk patients were included, with 162 starting aza and 108 patients allocated to continuous 5-aza (n=27) or HSCT (n=81). Three-year overall survival (OS) in aza was 32%, versus 50% in the HSCT arm, which was not significantly different, possibly due to insufficient statistical power. In contrast, three-year event-free survival (EFS) was significantly better in the HSCT arm (34%, versus 0%).

Nakamura et al. report the results of a multicentre, prospective, biologic assignment trial conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN)[1]. OS was analyzed at three years with the intention to treat: 260 patients in donor arm and 124 in non-donor arm. Adjusted three-year OS was significantly better in the donor arm (47.9%, versus 26.6%, p=.0001), as was EFS.

All patients in the European study and the majority (68%) of the BMT-CTN received hypomethylating agents (HMA). These studies were not designed to test the role of HMA before HSCT, but there was no evidence of aza benefit when given before HSCT. A complete remission was predictive for a better outcome in Kröger’s study, while a pre-graft therapy was deleterious in Nakamura’s Cox model for OS. Furthermore, in the European study, an unexpected high number of patients were “lost” between aza initiation and arm allocation.

To conclude, HSCT is able to improve life expectancy in higher risk IPSS MDS patients, now confirmed by three prospective studies. The role of somatic mutation, pre-graft or post-graft therapy in this algorithm, remains to be prospectively determined.

1. Nakamura R, Saber W, Martens MJ, Ramirez A, Scott B, Oran B, et al. Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome. J Clin Oncol. 2021 Jun 9;JCO2003380.

2. Kröger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, et al. Comparison Between 5-Azacytidine Treatment and Allogeneic Stem-Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability (VidazaAllo Study). J Clin Oncol. 2021 Jul 20;JCO2002724.

3. Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004 Jul 15;104(2):579–85.

4. Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013 Jul 20;31(21):2662–70.

5. Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G, et al. Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine. Biol Blood Marrow Transplant. 2012 Sep;18(9):1415–21.

6. Robin M, Porcher R, Adès L, Raffoux E, Michallet M, François S, et al. HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM. Leukemia. 2015 Jul;29(7):1496–501.