Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with GATA2-Related Myelodysplastic Syndrome

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.2033-2033
• Main Authors: Bortnick, Rachel, Wlodarski, Marcin, de Haas, Valerie, De Moerloose, Barbara, Dworzak, Michael, Hasle, Henrik, Masetti, Riccardo, Stary, Jan, Turkiewicz, Dominik, Ussowicz, Marek, Albert, Michael H., Bader, Peter, Bordon, Victoria, Claviez, Alexander, Kremens, Bernhard, Kühl, Jörn Sven, Lankester, Arjan C., Müller, Ingo, Pichler, Herbert, Sedlacek, Petr, Sykora, Karl-Walter, Zecca, Marco, Göhring, Gudrun, Locatelli, Franco, Noellke, Peter, Niemeyer, Charlotte M., Strahm, Brigitte
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-122403

Background GATA2 deficiency is an inherited immunodeficiency and predisposition syndrome with a high risk of developing myelodysplastic syndrome (MDS) early in life. Allogeneic hematopoietic stem cell transplantation (HSCT) is presently the only curative therapy for affected patients (pts), but to date there has been no larger study examining in detail outcomes after HSCT for GATA2-related pediatric MDS. Here we report the results of an analysis of pts with a germline GATA2 mutation undergoing HSCT for a diagnosis of MDS enrolled in the registry of the European Working Group of MDS in Childhood (EWOG-MDS). Patients and transplantation procedure Of the 87 pts with GATA2 deficiency registered before the age of 18 years, 66 underwent HSCT between 01/1997 and 11/2018. One pt had to be excluded from the analysis due to lack of data. The 65 remaining pts (34 males/31 females) were transplanted at a median age of 13.5 (4.6-19.9) years. Twenty-seven pts were transplanted for refractory cytopenia of childhood (RCC), while 38 pts had advanced disease. The highest bone marrow (BM) blast percentage prior to HSCT was 5-19% (n=23), 20-29% (n= 9) or >30% blasts (n=5); in one pt with myelofibrotic MDS a blast count was not attainable. Karyotypes included monosomy 7 (n=44), der (1;7) (n=4), trisomy 8 (n=4), random aberration (n=1) or a normal karyotype (n=12). Five of the 38 pts with an increased blast percentage had received intensive AML-type therapy prior to HSCT. Pts were grafted from a matched sibling donor (MSD; n=17), unrelated donor (UD; n=40) or a mismatched family donor (MMFD; n=8). The stem cell source was BM (n=37), peripheral blood (n=27) or cord blood (n=1). Pts were prepared with a busulfan-based (n=35), treosulfan-based (n=21), total body irradiation-based (n=5) or an alternative conditioning regimen (n=4). Results At 5 years the probability of overall survival (pOS) and disease-free survival (DFS) was 0.74 [0.62-0.86] and 0.69 [0.57-0.81], respectively, non-relapse mortality was 0.15 [0.08-0.27] and the cumulative incidence of relapse was 0.16 [0.09-0.29]. All pts engrafted initially. The cumulative incidence of acute graft versus host disease (GVHD) grade II-IV and III-IV was 0.34 [0.24-0.48] and 0.12 [0.06-0.24], respectively, and of overall and extensive chronic GVHD 0.25 [0.16-0.39] and 0.08 [0.03-0.20]. The most common post-transplant infections were viral (39 of the 43 pts with infections) with one pt each with EBV-related post-transplant lymphoproli