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1833 Interest of Cytoreductive Therapy before Allogenic Hematopoietic Stem Cell Transplantation in Childhood Myelodysplastic Syndromes: A Retrospective Study on Behalf of the Société Francophone De Greffe De Moelle Et De Thérapie Cellulaire (SFGM-TC)

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
MDS, Biological therapies, Chronic Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Transplantation
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Baptiste Le Calvez1,2*, Maxime Jullien, MD3,4*, Jean-Hugues Dalle5*, Cécile Renard, MD6*, Charlotte Jubert, MD7*, Arthur Sterin8*, Catherine Paillard9*, Anne Huynh, MD10*, Sarah Guenounou, MD11*, Benedicte Bruno12*, Virginie Gandemer13*, Nimrod Buchbinder14*, Pauline Simon15*, Cecile Pochon16*, Anne Sirvent, MD17*, Dominique Plantaz18*, Justyna Kanold19*, Fanny Rialland Battisti20* and Audrey Grain, MD1,2*

1Pediatric Hematology, Nantes, France
2Nantes University, Inserm UMR 1307, CNRS UMR 6075, Angers University, CRCI2NA, Nantes - France, Nantes, France
3Inserm UMR 1307, CNRS UMR 6075 - Team 12, Nantes University, Nantes, MD, France
4Nantes University Hospital, NANTES, France
5Department of Pediatric Hematology and Immunology, University Hospital Robert Debré, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France
6Institute of Hematology and Pediatric Oncology, Lyon, France
7Hématologie et oncologie pédiatrique, CHU de Bordeaux, Bordeaux Cedex, FRA
8APHM, La Timone Children Hospital, Department of Pediatric Hematology, Immunolog, Marseille, FRA
9CHRU Strasbourg, Strasbourg, FRA
10Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
11CHU de Toulouse - Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
12Chru Lille, Jeanne De Flandre Hématologie Pédiatrique, Lille, FRA
13CHU Hopital Sud, Rennes, FRA
14Rouen University Hospital, Rouen, FRA
15Hématologie et oncologie pédiatrique, CHRU de Besancon, Besancon, France
16Department of Hematology, Centre Hospitalier Régional Universitaire (CHRU), Vandoeuvre-les-Nancy, France
17CHU Montpellier, Montpellier, France
18CHU Grenoble, Grenoble, France
19CHU Clermont Ferrand, Clermontferrand, FRA
20Hématologie et oncologie pédiatrique, CHU Hôtel Dieu, Nantes, FRA


Pediatric myelodysplastic syndromes (cMDS) are rare and biologically different from that seen in adults. In addition to a specific genomic landscape, they are characterized by the high frequency of hypoplastic forms, and the recurrent association with germline predispositions (Khoury et al. 2022; Locatelli et Strahm 2018). For most patients, allogenic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option. In case of cMDS with increased blasts (cMDS-IB), pre-tranplant cytoreductive chemotherapy may be considered, but remains controversial (Strahm et al. 2011).


This multicenter retrospective study included all cMDS patients (<18y.o.) reported to the SFGM-TC registry who underwent an allo-HSCT between 2000 and 2020. Data have been obtained through ProMISe (internet-based system shared by all EBMT transplantation centers). All patients have given signed informed consent.


Eighty-four cMDS patients from 17 centers were included. Median age at transplant was 10.2 years (IQR: 7.2, 14.2). Fifty-two percent of patients presented with increased blasts at diagnosis. Germline predispositions were known in 24% of patients. GATA 2 mutations were the most frequent (14%). Eighty-two percent of patients presented with hematologic cytogenetic abnormalities, including 64% of monosomy 7. Myeloablative conditioning was used in most of cases (91%). Busulfan/melphalan was the most frequent conditioning regimen (58%). HSCT were performed from sibling donors in 29% of the cases, matched unrelated donors (MUD) in 44%, umbilical cord blood (UCB) in 21% and haploidentical in 6%. Stem cell source was bone marrow in 68% of the cases.

Considering the whole cohort, 5y overall survival (OS) and disease-free survival (DFS) were 67% (IC95% 57-78%) and 63% (IC95% 54-74%) respectively (Figure 1). Five years cumulative incidences of non-relapse mortality (NRM) and relapse were 26% (IC95% 17-35%) and 12% (IC95% 5.6-20%) respectively. Of the 21 cases of reported toxic death, 15 were related to acute GVH (aGVHD). Six months cumulative incidences of grade II-IV and III-IV acute graft vs host disease were 46 % and 24 % respectively. In univariate analysis, patients under 12 years (p=0,018) or who received a BuCyMel conditioning (p=0,004) or a graft from a MUD (p=0,030) had worst 5y OS and PFS. As expected, OS increased with time (p=0,014) reflecting improvements in supportive care and HSCT procedures (Figure 2A). These results were confirmed in multivariate analysis, except for MUD.

Twenty-four patients received pre-transplant cytoreductive therapy, most often intensive chemotherapy (20/24). In the overall population, pre-transplant cytoreduction was not associated with an improved survival. However, subgroup analysis of the 40 patients with cMDS-IB showed a significant improvement of the OS probability (HR 0.18 [0.04-0.83], p=0.014) in patients who received a pre-transplant cytoreductive therapy in univariate analysis (Figure 2B). Cytoreductive therapy did not appear to be associated with a reduced risk of relapse, but with a lower risk of NRM. Although not statistically significant, the incidence of aGVHD was higher in patients who did not receive any cytoreductive therapy (HR 0.60 [0.09-3.85]).


This retrospective study reports the outcomes of 84 patients who underwent allo-HCT for childhood MDS. This study seems to show a benefit associated with the pre-transplant cytoreduction therapy in the subgroup of patients with cMDS-IB, notably through a reduction of aGVHD and NRM occurrence. BuCyMel conditioning, currently recommended for cMDS-IB, appears here, to be associated with excess of toxic mortality. This study also confirms the high aGVH-related toxic mortality rates already reported in cMDS (Strahm et al. 2011). Recent retrospective data have shown a benefit of post-transplantation cyclophosphamide (PTCy) in GATA2 patients transplanted with sibling or matched unrelated donors (Nichols‐Vinueza et al. 2022). Prospective data on the use of PTCy in cMDS are therefore needed.


This research is funded by the non-profit organization Etoile de Martin/SFCE.

Disclosures: Dalle: Jazz Pharmaceuticals: Honoraria. Huynh: Medac: Other: Advisory board; Astellas: Other: Advisory board; Jazz: Other: travel fees, advisory board; Pfizer: Other: advisory board; Servier: Other: Advisory board; Neovii: Other: Advisory board; Novartis: Other: travel fees, advisory board.

*signifies non-member of ASH