Abstract
This retrospective study aimed to investigate the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) for childhood myelodysplastic syndrome (MDS). Thirty-six patients (low-grade MDS, 24; advanced MDS, 12) received HSCT at the Asan Medical Center over two decades (early period, 1997–2007; recent period, 2008–2017). The transplantation outcomes were analyzed according to disease status, conditioning regimen, various donor types, and period of HSCT. During a median follow-up of 5.6 (range, 1.4–21.1) years, the probability of overall survival (OS) and failure-free survival was 77% and 69%, respectively. The cumulative incidence of transplantation-related mortality (TRM) was 12%. Significantly reduced TRM and improved OS were observed in patients who received HSCT during the recent period vs. the early period (TRM, 4% vs. 30%, P = 0.021; OS, 87% vs. 50%, P = 0.006). Comparable outcomes were observed for HSCT from haploidentical family donors vs. HLA-identical donors (TRM, 10% vs. 14%, P = 0.837; OS, 86% vs. 79%, P = 0.625). This study identified the improved outcomes of allogeneic HSCT for childhood MDS over time, in addition, the feasible outcomes of haploidentical HSCT suggested its use as an attractive alternative in the future procedures.
Similar content being viewed by others
References
Hasle H, Wadsworth LD, Massing BG, McBride M, Schultz KR. A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada. Br J Haematol. 1999;106:1027–32.
Niemeyer CM, Baumann I. Classification of childhood aplastic anemia and myelodysplastic syndrome. Hematol Am Soc Hematol Educ Program. 2011;2011:84–9.
Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17:277–82.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissue, 4th ed. Lyon, France: IARC; 2008.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.
Hasle H. Myelodysplastic and myeloproliferative disorders of childhood. Hematol Am Soc Hematol Educ Program. 2016;2016:598–604.
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 Transpl. 2015;21:565–9.
Hasegawa D, Chen X, Hirabayashi S, Ishida Y, Watanabe S, Zaike Y, et al. Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification. Br J Haematol. 2014;166:758–66.
Andolina JR, Kletzel M, Tse WT, Jacobsohn DA, Duerst RE, Schneiderman J, et al. Allogeneic hematopoetic stem cell transplantation in pediatric myelodysplastic syndromes: improved outcomes for de novo disease. Pediatr Transpl. 2011;15:334–43.
Strahm B, Locatelli F, Bader P, Ehlert K, Kremens B, Zintl F, et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transpl. 2007;40:329–33.
Yusuf U, Frangoul HA, Gooley TA, Woolfrey AE, Carpenter PA, Andrews RG, et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transpl. 2004;33:805–14.
Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR, et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 2003;102:1997–2003.
Sasaki H, Manabe A, Kojima S, Tsuchida M, Hayashi Y, Ikuta K, et al. Myelodysplastic syndrome in childhood: a retrospective study of 189 patients in Japan. Leukemia 2001;15:1713–20.
Woods WG, Barnard DR, Alonzo TA, Buckley JD, Kobrinsky N, Arthur DC, et al. Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children’s Cancer Group. J Clin Oncol. 2002;20:434–40.
Galaverna F, Ruggeri A, Locatelli F. Myelodysplastic syndromes in children. Curr Opin Oncol. 2018;30:402–8.
Locatelli F, Strahm B. How I treat myelodysplastic syndromes of childhood. Blood. 2018;131:1406–14.
Gohring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA, et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116:3766–9.
Moriwaki K, Manabe A, Taketani T, Kikuchi A, Nakahata T, Hayashi Y. Cytogenetics and clinical features of pediatric myelodysplastic syndrome in Japan. Int J Hematol. 2014;100:478–84.
Hofmann I. Pediatric myelodysplastic syndromes. J Hematopathol. 2015;8:127–41.
Im HJ, Koh KN, Seo JJ. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents. Blood Res. 2016;51:8–16.
Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, et al. Haploidentical HCT using an alphabeta T-cell-depleted graft with targeted alphabeta(+) cells by add-back after a reduced intensity preparative regimen containing low-dose TBI. Bone Marrow Transpl. 2016;51:1217–22.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on Acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl. 2005;11:945–56.
Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Exp Opin Pharmacother. 2014;15:23–36.
Maruyama K, Aotsuka N, Kumano Y, Sato N, Kawashima N, Onda Y, et al. Immune-mediated hematopoietic failure after allogeneic hematopoietic stem cell transplantation: a common cause of late graft failure in patients with complete donor chimerism. Biol Blood Marrow Transpl. 2018;24:43–9.
Munoz A, Diaz-Heredia C, Badell I, Bureo E, Gomez P, Martinez A, et al. Allogeneic stem cell transplantation for myelodysplastic syndromes in children: a report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON). Pediatr Hematol Oncol. 2009;26:345–55.
Kook H, Kim CJ, Yoon WS, Ryu NE, Chung KJ, Hwang TJ. A clinical study of pediatric myelodysplastic syndrome:application of international prognostic scoring system and the review of the Korean literature. J Korean Cancer Assoc. 2000;32:178–90.
Lee J, Kim SY, Cho B, Jang PS, Chung NK, Kim HK. Short-term results of hematopoietic stem cell transplantation for children with myelodysplastic syndrome. J Korean Pediatr Soc. 2002;45:370–5.
Basquiera AL, Pizzi S, Correas AG, Longo PG, Goldman WC, Prates MV, et al. Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina. Pediatr Blood Cancer. 2015;62:153–7.
Strahm B, Nollke P, Zecca M, Korthof ET, Bierings M, Furlan I, et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25:455–62.
Webb DK, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM. Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990–99. Br J Haematol. 2002;117:33–9.
Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C, et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol. 2011;12:1214–21.
Rocha V, Kabbara N, Ionescu I, Ruggeri A, Purtill D, Gluckman E. Pediatric related and unrelated cord blood transplantation for malignant diseases. Bone Marrow Transpl. 2009;44:653–9.
Hasle H, Baumann I, Bergstrasser E, Fenu S, Fischer A, Kardos G, et al. The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML). Leukemia. 2004;18:2008–14.
Trobaugh-Lotrario AD, Kletzel M, Quinones RR, McGavran L, Proytcheva MA, Hunger SP, et al. Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT). Bone Marrow Transpl. 2005;35:143–9.
Hasle H. Myelodysplastic syndromes in childhood-classification, epidemiology, and treatment. Leuk Lymphoma. 1994;13:11–26.
Parikh SH, Mendizabal A, Martin PL, Prasad VK, Szabolcs P, Driscoll TA, et al. Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience. Biol Blood Marrow Transpl. 2009;15:948–55.
Woodard P, Carpenter PA, Davies SM, Gross TG, He W, Zhang MJ, et al. Unrelated donor bone marrow transplantation for myelodysplastic syndrome in children. Biol Blood Marrow Transpl. 2011;17:723–8.
Acknowledgements
This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yoo, J.W., Im, H.J., Kim, H. et al. Improved outcomes of allogeneic hematopoietic stem cell transplantation including haploidentical transplantation for childhood myelodysplastic syndrome. Bone Marrow Transplant 55, 1595–1603 (2020). https://doi.org/10.1038/s41409-020-0814-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-020-0814-8
- Springer Nature Limited
This article is cited by
-
Decitabine-containing conditioning improved outcomes for children with higher-risk myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation
Annals of Hematology (2024)
-
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 Pediatrics (2022)
-
Comparative analysis of Decitabine intensified BUCY2 and BUCY2 conditioning regimen for high-risk MDS patients undergoing allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation (2022)