Hematopoietic cell transplantation for pediatric myelodysplastic syndromes
DOI:
https://doi.org/10.46765/2675-374X.2025v6n1e289Keywords:
Myelodysplastic Syndromes, Hematopoietic Stem Cell Transplantation, ChildAbstract
Myelodysplastic syndromes (MDS) are uncommon in children and present distinct features compared to adults. Allogeneic hematopoietic cell transplantation (HCT) is considered the standard curative treatment for many children with MDS, including all patients with MDS with excess of blasts and those with refractory cytopenia of childhood associated with unfavorable karyotype, severe neutropenia or transfusion dependence. In this article, we reviewed the indications of HCT in pediatric MDS.
References
1. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, Head DR. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277–82. https://doi.org/10.1038/sj.leu.2402765 DOI: https://doi.org/10.1038/sj.leu.2402765
2. Locatelli F, Strahm B. How I treat myelodysplastic syndromes of childhood. Blood. 2018;131(13):1406–14. https://doi.org/10.1182/blood-2017-09-765214 DOI: https://doi.org/10.1182/blood-2017-09-765214
3. Passmore SJ, Chessells JM, Kempski H, Hann IM, Brownbill PA, Stiller CA. Paediatric myelodysplastic
syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival. Br J Haematol. 2003;121(5):758–67. https://doi.org/10.1046/j.1365-2141.2003.04361.x DOI: https://doi.org/10.1046/j.1365-2141.2003.04361.x
4. Babcock S, Calvo KR, Hasserjian RP. Pediatric myelodysplastic syndrome. Semin Diagn Pathol. 2023; 40(3):152–71. https://doi.org/10.1053/j.semdp.2023.04.006 DOI: https://doi.org/10.1053/j.semdp.2023.04.006
5. Galaverna F, Ruggeri A, Locatelli F. Myelodysplastic syndromes in children. Curr Opin Oncol. 2018; 30(6):402–8. https://doi.org/10.1097/CCO.0000000000000488 DOI: https://doi.org/10.1097/CCO.0000000000000488
6. Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR. The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia. Virchows Arch. 2023;482(1):113–30. https://doi.org/10.1007/s00428-022-03447-9 DOI: https://doi.org/10.1007/s00428-022-03447-9
7. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, Bejar R, Berti E, Busque L, Chan JKC, Chen W, Chen X, Chng WJ, Choi JK, Colmenero I, Coupland SE, Cross NCP, De Jong D, Elghetany MT, Takahashi E, Emile JF, Ferry J, Fogelstrand L, Fontenay M, Germing U, Gujral S, Haferlach T, Harrison C, Hodge JC, Hu S, Jansen JH, Kanagal-Shamanna R, Kantarjian HM, Kratz CP, Li XQ, Lim MS, Loeb K, Loghavi S, Marcogliese A, Meshinchi S, Michaels P, Naresh KN, Natkunam Y, Nejati R, Ott G, Padron E, Patel KP, Patkar N, Picarsic J, Platzbecker U, Roberts I, Schuh A, Sewell W, Siebert R, Tembhare P, Tyner J, Verstovsek S, Wang W, Wood B, Xiao W, Yeung C, Hochhaus A. The 5th edition of the World Health Organization Classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703–19. https://doi.org/10.1038/s41375-022-01613-1 DOI: https://doi.org/10.1038/s41375-022-01613-1
8. Kennedy AL, Shimamura A. Genetic predisposition to MDS: clinical features and clonal evolution. Blood. 2019;133(10):1071–85. https://doi.org/10.1182/blood-2018-10-844662 DOI: https://doi.org/10.1182/blood-2018-10-844662
9. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. https://doi.org/10.1182/blood-2016-03-643544 DOI: https://doi.org/10.1182/blood-2016-03-643544
10. Sahoo SS, Kozyra EJ, Wlodarski MW. Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes. Best Pract Res Clin Haematol. 2020; 33(3):101197. https://doi.org/10.1016/j.beha.2020.101197 DOI: https://doi.org/10.1016/j.beha.2020.101197
11. Seber A, Villela NC, Gouveia RV. Tratamento com transplante de medula óssea. In: Lopes LF, editor. Mielodisplasia em pediatria. São Paulo: Lemar Goi; 2019. p. 283–94.
12. Hasegawa D, Chen X, Hirabayashi S, Ishida Y, Watanabe S, Zaike Y, Tsuchida M, Masunaga A, Yoshimi A, Hama A, Kojima S, Ito M, Nakahata T, Manabe A. Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification. Br J Haematol. 2014;166(5):758–66. https://doi.org/10.1111/bjh.12955 DOI: https://doi.org/10.1111/bjh.12955
13. Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR, Starý J, Schmitt-Graeff A, Fischer A, Harbott J, Chessells JM, Hann I, Fenu S, Rajnoldi AC, Kerndrup G, Van Wering E, Rogge T, Nollke P, Niemeyer CM. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood. 2003;102(6):1997–2003. https://doi.org/10.1182/blood-2002-11-3444 DOI: https://doi.org/10.1182/blood-2002-11-3444
14. Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I, Sedlacek P, Chybicka A, Schmugge M, Bordon V, Peters C, O’Marcaigh A, de Heredia CD, Bergstraesser E, Moerloose BD, van den Heuvel Eibrink MM, Starý J, Trebo M, Wojcik D, Niemeyer CM, Locatelli F; EWOG-MDS study group. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25(3):455–62. https://doi.org/10.1038/leu.2010.297 DOI: https://doi.org/10.1038/leu.2010.297
15. Inagaki J, Fukano R, Kurauchi K, Noguchi M, Tanioka S, Okamura J. Hematopoietic stem cell transplantation in children with refractory cytopenia of childhood: single-center experience using high-dose cytarabine containing myeloablative and aplastic anemia oriented reduced-intensity conditioning regimens. Biol Blood Marrow Transplant. 2015;21(3):565–9. https://doi.org/10.1016/j.bbmt.2014.12.003 DOI: https://doi.org/10.1016/j.bbmt.2014.12.003
16. Strahm B, Locatelli F, Bader P, Ehlert K, Kremens B, Zintl F, Führer M, Stachel D, Sykora KW, Sedlacek P, Baumann I, Niemeyer CM. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant. 2007;40(4):329–33. https://doi.org/10.1038/sj.bmt.1705730 DOI: https://doi.org/10.1038/sj.bmt.1705730
17. Quintero V, Bueno-Sánchez D, Mozo-Del-Castillo Y, Urtasun-Erburu A, Sisinni L, López-Duarte M, Pérez-Hurtado JM, Fuster JL, González-Vicent M, Pérez-Martínez A, Diaz-de-Heredia C; Grupo Español de Trasplante de Médula ósea en Niños (GETMON)/Grupo Español de Trasplante Hematopoyético (GETH) and Grupo de Insuficiencias Medulares de la Sociedad Española de Hematología y Oncología Pediátricas (SEHOP). Haploidentical hematopoietic stem cell transplantation in pediatric patients with acquired hypocellular bone marrow failure. Transplant Cell Ther. 2023;29(10):621.e1–e6. https://doi.org/10.1016/j.jtct.2023.07.011 DOI: https://doi.org/10.1016/j.jtct.2023.07.011
18. Guidelines for Hematopoietic Stem Cell Transplantation in Childhood MDS and JMML for Patients enrolled in EWOG-MDS Studies. Freiburg: EWOG-MDS Consensus Conference; 2017.
19. Eapen M, Brazauskas R, Hemmer M, Perez WS, Steinert P, Horowitz MM, Deeg HJ. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018;2(16):2095–103. https://doi.org/10.1182/bloodadvances.2018021980 DOI: https://doi.org/10.1182/bloodadvances.2018021980
20. Truscott L, Pariury H, Hanmod S, Davini M, de la Maza M, Sapp LN, Staples K, Proytcheva M, Katsanis E. Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatr Blood Cancer. 2023;70(2):e30102. https://doi.org/10.1002/pbc.30102 DOI: https://doi.org/10.1002/pbc.30102
21. Madureira AB, Eapen M, Locatelli F, Teira P, Zhang MJ, Davies SM, Picardi A, Woolfrey A, Chan KW, Socié G, Vora A, Bertrand Y, Sales-Bonfim CM, Gluckman E, Niemeyer C, Rocha V; Eurocord-European Blood and Marrow Transplant Group; Center of International Blood and Marrow Transplant Registry; European Working Group on childhood MDS. Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation. Leukemia. 2011;25(3):449–54. https://doi.org/10.1038/leu.2010.285 DOI: https://doi.org/10.1038/leu.2010.285
22. Suo P, Wang S, Xue Y, Cheng Y, Kong J, Yan C, Zhao X, Chen Y, Han W, Xu L, Zhang X, Liu K, Zhang L, Huang X, Wang Y. Unmanipulated haploidentical hematopoietic stem cell transplantation for children with myelodysplastic syndrome. Pediatr Transplant. 2020;24(7):e13864. https://doi.org/10.1111/petr.13864 DOI: https://doi.org/10.1111/petr.13864
23. Merli P, Pagliara D, Mina T, Bertaina V, Li Pira G, Lazzaro S, Biagini S, Galaverna F, Strocchio L, Carta R, Catanoso ML, Quagliarella F, Becilli M, Boccieri E, Del Bufalo F, Panigari A, Agostini A, Pedace L, Pizzi S, Perotti C, Algeri M, Zecca M, Locatelli F. αβT- and B-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation in children with myelodysplastic syndromes. Haematologica. 2022;107(12):2966–71. https://doi.org/10.3324/haematol.2022.280698 DOI: https://doi.org/10.3324/haematol.2022.280698
24. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008;26(15):2505–11. https://doi.org/10.1200/JCO.2007.11.9214 DOI: https://doi.org/10.1200/JCO.2007.11.9214
25. Yoshimi A, Baumann I, Führer M, Bergsträsser E, Göbel U, Sykora KW, Klingebiel T, Gross-Wieltsch U, van den Heuvel-Eibrink MM, Fischer A, Nöllke P, Niemeyer C. Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia. Haematologica. 2007;92(3):397–400. https://doi.org/10.3324/haematol.10683 DOI: https://doi.org/10.3324/haematol.10683
26. Göhring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA, Kerndrup G, Sainati L, Bergstraesser E, Hasle H, Stary J, Trebo M, van den Heuvel-Eibrink MM, Zecca M, van Wering ER, Fischer A, Noellke P, Strahm B, Locatelli F, Niemeyer CM, Schlegelberger B. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766–9. https://doi.org/10.1182/blood-2010-04-280313 DOI: https://doi.org/10.1182/blood-2010-04-280313
27. Jaiswal SR, Zaman S, Chakrabarti A, Sen S, Mukherjee S, Bhargava S, Ray K, O’Donnell PV, Chakrabarti
S. Improved outcome of refractory/relapsed acute myeloid leukemia after post-transplantation cyclophosphamide-based haploidentical transplantation with myeloablative conditioning and early prophylactic granulocyte colony-stimulating factor-mobilized donor lymphocyte infusions. Biol Blood Marrow Transplant. 2016;22(10):1867–73. https://doi.org/10.1016/j.bbmt.2016.07.016 DOI: https://doi.org/10.1016/j.bbmt.2016.07.016
28. Le Calvez B, Jullien M, Dalle JH, Renard C, Jubert C, Sterin A, Paillard C, Huynh A, Guenounou S, Bruno B, Gandemer V, Buchbinder N, Simon P, Pochon C, Sirvent A, Plantaz D, Kanold J, Béné MC, Rialland F, Grain A; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM‐TC). Childhood myelodysplastic syndromes: Is cytoreductive therapy useful before allogeneic hematopoietic stem cell transplantation? Hemasphere. 2024;8(7):e120. https://doi.org/10.1002/hem3.120 DOI: https://doi.org/10.1002/hem3.120
29. Smith AR, Christiansen EC, Wagner JE, Cao Q, MacMillan ML, Stefanski HE, Trotz BA, Burke MJ, Verneris MR. Early hematopoietic stem cell transplant is associated with favorable outcomes in children with MDS. Pediatr Blood Cancer. 2013;60(4):705–10. https://doi.org/10.1002/pbc.24390 DOI: https://doi.org/10.1002/pbc.24390
30. Gao J, Hu Y, Gao L, Xiao P, Lu J, Hu S. The effect of decitabine-combined minimally myelosuppressive regimen bridged allo-HSCT on the outcomes of pediatric MDS from 10 years’ experience of a single center. BMC Pediatr. 2022;22(1):312. https://doi.org/10.1186/s12887-022-03376-1 DOI: https://doi.org/10.1186/s12887-022-03376-1
31. Waespe N, Van Den Akker M, Klaassen RJ, Lieberman L, Irwin MS, Ali SS, Abdelhaleem M, Zlateska B, Liebman M, Cada M, Schechter T, Dror Y. Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation. Haematologica. 2016;101(12):1508–15. https://doi.org/10.3324/haematol.2016.145821 DOI: https://doi.org/10.3324/haematol.2016.145821
32. Locatelli F, Strålin KB, Schmid I, Sevilla J, Smith OP, van den Heuvel-Eibrink MM, Zecca M, Zwaan CM, Gaudy A, Patturajan M, Poon J, Simcock M, Niemeyer CM. Efficacy and safety of azacitidine in pediatric patients with newly diagnosed advanced myelodysplastic syndromes before hematopoietic stem cell transplantation in the AZA-JMML-001 trial. Pediatr Blood Cancer. 2024;71(5):e30931. https://doi.org/10.1002/pbc.30931 DOI: https://doi.org/10.1002/pbc.30931
33. Masetti R, Baccelli F, Leardini D, Locatelli F. Venetoclax: a new player in the treatment of children with high-risk myeloid malignancies? Blood Adv. 2024;8(13):3583–95. https://doi.org/10.1182/bloodadvances.2023012041 DOI: https://doi.org/10.1182/bloodadvances.2023012041
34. Guillaume T, Thépot S, Peterlin P, Ceballos P, Bourgeois AL, Garnier A, Orvain C, Giltat A, François S, Bris YL, Fronteau C, Planche L, Chevallier P. Prophylactic or preemptive low-dose azacitidine and donor lymphocyte infusion to prevent disease relapse following allogeneic transplantation in patients with high-risk acute myelogenous leukemia or myelodysplastic syndrome. Transplant Cell Ther. 2021;27(10):839.e1–e6. https://doi.org/10.1016/j.jtct.2021.06.029 DOI: https://doi.org/10.1016/j.jtct.2021.06.029
35. Min GJ, Park SS, Park S, Yoon JH, Lee SE, Cho BS, Eom KS, Kim HJ, Lee S, Min CK, Cho SG, Kim YJ. Beneficial effects of cellular immunotherapy in the prevention and treatment of posttransplant hematologic relapse of myelodysplastic neoplasms. Ann Hematol. 2024;103(12):5261–72. https://doi.org/10.1007/s00277-024-06060-9 DOI: https://doi.org/10.1007/s00277-024-06060-9
36. Tan JL, Curtis DJ, Muirhead J, Swain MI, Fleming SA, Cirone B, O’Brien ME, Wong SM, Inam S, Patil S, Spencer A. CD34 chimerism directed donor lymphocyte infusion with or without azacitidine results in reduced relapse and superior overall survival when full donor chimerism is achieved in allogeneic stem cell transplant recipients with acute myeloid leukaemia/myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk. 2024;24(11):e852–60. https://doi.org/10.1016/j.clml.2024.07.006 DOI: https://doi.org/10.1016/j.clml.2024.07.006
37. Qi SS, Chen Z, Du Y, Sun M, Wang Z, Long F, Luo L, Xiong H. Prophylactic donor lymphocyte infusion after haploidentical hematopoietic cell transplantation and post-transplant cyclophosphamide for treatment of high-risk myeloid neoplasms in children: A retrospective study. Pediatr Blood Cancer. 2023;70(11):e30659. https://doi.org/10.1002/pbc.30659 DOI: https://doi.org/10.1002/pbc.30659
38. Oshrine BR, Shyr D, Hale G, Petrovic A. Low-dose azacitidine for relapse prevention after allogeneic hematopoietic cell transplantation in children with myeloid malignancies. Pediatr Transplant. 2019;23(4):e13423. https://doi.org/10.1111/petr.13423 DOI: https://doi.org/10.1111/petr.13423
39. Finke J, Schmoor C, Bertz H, Marks R, Wäsch R, Zeiser R, Hackanson B. Long-term follow-up of therapyrelated myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2016;51(6):771–7. https://doi.org/10.1038/bmt.2015.338 DOI: https://doi.org/10.1038/bmt.2015.338
40. Kida M, Usuki K, Uchida N, Fukuda T, Katayama Y, Kondo T, Eto T, Matsuoka KI, Matsuhashi Y, Ota S, Sawa M, Miyamoto T, Ichinohe T, Kimura T, Atsuta Y, Takami A, Miyazaki Y, Yano S, Ishiyama K, Yanada M, Aoki J. Outcome and risk factors for therapy-related myeloid neoplasms treated with allogeneic stem cell transplantation in japan. biol blood marrow transplant. 2020;26(8):1543–51. https://doi.org/10.1016/j.bbmt.2020.04.004 DOI: https://doi.org/10.1016/j.bbmt.2020.04.004
41. Sharma A, Huang S, Li Y, Brooke RJ, Ahmed I, Allewelt HB, Amrolia P, Bertaina A, Bhatt NS, Bierings MB, Bies J, Brisset C, Brondon JE, Dahlberg A, Dalle JH, Eissa H, Fahd M, Gassas A, Gloude NJ, Goebel WS, Goeckerman ES, Harris K, Ho R, Hudspeth MP, Huo JS, Jacobsohn D, Kasow KA, Katsanis E, Kaviany S, Keating AK, Kernan NA, Ktena YP, Lauhan CR, López-Hernandez G, Martin PL, Myers KC, Naik S, Olaya Vargas A, Onishi T, Radhi M, Ramachandran S, Ramos K, Rangarajan HG, Roehrs PA, Sampson ME, Shaw PJ, Skiles JL, Somers K, Symons HJ, de Tersant M, Uber AN, Versluys B, Cheng C, Triplett BM. Outcomes of pediatric patients with therapy-related myeloid neoplasms. Bone Marrow Transplant. 2021;56(12):2997–3007. https://doi.org/10.1038/s41409-021-01448-x DOI: https://doi.org/10.1038/s41409-021-01448-x
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Neysimelia Costa Villela, Anita Frisanco Oliveira, Roseane Vasconcelos Gouveia, Mariane Farherr Caleff, Gabriela Gaspar Filgueiras Landi, Maria Lúcia de Martino Lee
This work is licensed under a Creative Commons Attribution 4.0 International License.
