Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Allogeneic hematopoietic cell transplantation in patients with juvenile myelomonocytic leukemia in Korea: a report of the Korean Pediatric Hematology-Oncology Group


Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. This multicenter study evaluated the characteristics, outcomes, and prognostic factors of allogeneic hematopoietic cell transplantation (HCT) in recipients with JMML who were diagnosed between 2000 and 2019 in Korea. Sixty-eight patients were retrospectively enrolled—28 patients (41.2%) received HCT during 2000–2010 and 40 patients (58.8%) during 2011–2020. The proportion of familial mismatched donors increased from 3.6 to 37.5%. The most common conditioning therapy was changed from Busulfan/Cyclophosphamide-based to Busulfan/Fludarabine-based therapy. The 5-year probabilities of event-free survival (EFS) and overall survival (OS) were 52.6% and 62.3%, respectively. The 5-year incidence of transplant-related mortality was 30.1%. Multivariate analysis revealed that the proportion of hemoglobin F ≥ 40%, abnormal cytogenetics, and matched sibling donors were independent risk factors for a higher relapse rate. Patients whose donor chimerism was below 99% had a significantly higher relapse rate. Better OS and lower treatment-related mortality were observed in patients with chronic graft-versus-host disease (GVHD), whereas grade III or IV acute GVHD was associated with worse EFS. In conclusion, the number of transplant increased along with the increase in alternative donor transplants, nevertheless, similar results were maintained. Alternative donor transplantation should be encouraged.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Cumulative incidence (CI) of relapse.
Fig. 2: Cumulative incidence (CI) of relapse.
Fig. 3: Acute graft-versus-host disease (aGVHD) and outcomes.
Fig. 4: Chronic graft-versus-host disease (cGVHD) and outcomes.

Data availability

All the collected medical information was stored in the Internet-based Clinical Research and Trial Management System of the Korea Disease Control and Prevention Agency. The data that support the findings of this study are available from the corresponding author upon reasonable request.


  1. Stieglitz E, Mazor T, Olshen AB, Geng H, Gelston LC, Akutagawa J, et al. Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia. Nat Commun. 2017;8:2127.

    Article  Google Scholar 

  2. Locatelli F, Algeri M, Merli P, Strocchio L. Novel approaches to diagnosis and treatment of Juvenile Myelomonocytic Leukemia. Expert Rev Hematol. 2018;11:129–43.

    Article  CAS  Google Scholar 

  3. Niemeyer CM, Flotho C. Juvenile myelomonocytic leukemia: who’s the driver at the wheel? Blood 2019;133:1060–70.

    Article  CAS  Google Scholar 

  4. Sanders JE, Buckner CD, Stewart P, Thomas ED. Successful treatment of juvenile chronic granulocytic leukemia with marrow transplantation. Pediatrics 1979;63:44–6.

    Article  CAS  Google Scholar 

  5. Flotho C, Sommer S, Lübbert M. DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia. Semin Cancer Biol. 2018;51:68–79.

    Article  CAS  Google Scholar 

  6. Locatelli F, Nöllke P, Zecca M, Korthof E, Lanino E, Peters C, et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood 2005;105:410–9.

    Article  CAS  Google Scholar 

  7. Park HD, Lee SH, Sung KW, Koo HH, Jung NG, Cho B, et al. Gene mutations in the Ras pathway and the prognostic implication in Korean patients with juvenile myelomonocytic leukemia. Ann Hematol. 2012;91:511–7.

    Article  CAS  Google Scholar 

  8. 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.

    CAS  Google Scholar 

  9. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401.e1.

    Article  Google Scholar 

  10. Chan RJ, Cooper T, Kratz CP, Weiss B, Loh ML. Juvenile myelomonocytic leukemia: a report from the 2nd International JMML Symposium. Leuk Res. 2009;33:355–62.

    Article  Google Scholar 

  11. Tüfekçi Ö, Koçak Ü, Kaya Z, Yenicesu İ, Albayrak C, Albayrak D, et al. Juvenile myelomonocytic leukemia in Turkey: a retrospective analysis of sixty-five patients. Turk J Haematol. 2018;35:27–34.

    Article  Google Scholar 

  12. Niemeyer CM, Arico M, Basso G, Biondi A, Cantu Rajnoldi A, Creutzig U, et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Blood 1997;89:3534–43.

    CAS  PubMed  Google Scholar 

  13. Manabe A, Okamura J, Yumura-Yagi K, Akiyama Y, Sako M, Uchiyama H, et al. Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group. Leukemia 2002;16:645–9.

    Article  CAS  Google Scholar 

  14. Korthof ET, Snijder PP, de Graaff AA, Lankester AC, Bredius RG, Ball LM, et al. Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients. Bone Marrow Transpl. 2005;35:455–61.

    Article  CAS  Google Scholar 

  15. Stieglitz E, Ward AF, Gerbing RB, Alonzo TA, Arceci RJ, Liu YL, et al. Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2015;62:629–36.

    Article  CAS  Google Scholar 

  16. Helsmoortel HH, Bresolin S, Lammens T, Cavé H, Noellke P, Caye A, et al. LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia. Blood 2016;127:1163–72.

    Article  CAS  Google Scholar 

  17. Olk-Batz C, Poetsch AR, Nöllke P, Claus R, Zucknick M, Sandrock I, et al. Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia with poor outcome. Blood 2011;117:4871–80.

    Article  CAS  Google Scholar 

  18. Yoshida N, Sakaguchi H, Yabe M, Hasegawa D, Hama A, Hasegawa D, et al. Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia: A Report from the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2020;26:902–10.

    Article  CAS  Google Scholar 

  19. Niemeyer CM, Flotho C, Lipka DB, Starý J, Rössig C, Baruchel A, et al. Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial. Blood Adv. 2021;5:2901–8.

    Article  CAS  Google Scholar 

  20. Niemeyer CM, Loh ML, Cseh A, Cooper T, Dvorak CC, Chan R, et al. Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia. Haematologica 2015;100:17–22.

    Article  Google Scholar 

  21. Inagaki J, Fukano R, Nishikawa T, Nakashima K, Sawa D, Ito N, et al. Outcomes of immunological interventions for mixed chimerism following allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia. Pediatr Blood Cancer. 2013;60:116–20.

    Article  Google Scholar 

  22. Yoshimi A, Niemeyer CM, Bohmer V, Duffner U, Strahm B, Kreyenberg H, et al. Chimaerism analyses and subsequent immunological intervention after stem cell transplantation in patients with juvenile myelomonocytic leukaemia. Br J Haematol. 2005;129:542–9.

    Article  Google Scholar 

  23. Matsuda K, Shimada A, Yoshida N, Ogawa A, Watanabe A, Yajima S, et al. Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. Blood 2007;109:5477–80.

    Article  CAS  Google Scholar 

  24. Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, et al. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015;47:1326–33.

    Article  CAS  Google Scholar 

  25. Yabe M, Ohtsuka Y, Watanabe K, Inagaki J, Yoshida N, Sakashita K, et al. Transplantation for juvenile myelomonocytic leukemia: a retrospective study of 30 children treated with a regimen of busulfan, fludarabine, and melphalan. Int J Hematol. 2015;101:184–90.

    Article  CAS  Google Scholar 

  26. Sakashita K, Matsuda K, Koike K. Diagnosis and treatment of juvenile myelomonocytic leukemia. Pediatr Int. 2016;58:681–90.

    Article  Google Scholar 

  27. Locatelli F, Niemeyer C, Angelucci E, Bender-Götze C, Burdach S, Ebell W, et al. Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood. J Clin Oncol. 1997;15:566–73.

    Article  CAS  Google Scholar 

  28. Dvorak CC, Satwani P, Stieglitz E, Cairo MS, Dang H, Pei Q, et al. Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children’s Oncology Group study. Pediatr Blood Cancer. 2018;65:e27034.

    Article  Google Scholar 

  29. Locatelli F, Crotta A, Ruggeri A, Eapen M, Wagner JE, Macmillan ML, et al. Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study. Blood 2013;122:2135–41.

    Article  CAS  Google Scholar 

Download references


This study was supported by a grant from the Korea Childhood Leukemia Foundation and the Korean Pediatric Hematology-Oncology Group (2020). We also thank the Korea Disease Control and Prevention Agency for providing the Internet-based Clinical Research and Trial Management System for storing medical information online.

Author information

Authors and Affiliations



BC, HJK, HK, YTL, and KHY designed this study. ESY, SKK, HYJ, JWL, BKK, HJB, EJY, WKA, SMH, SKP, and ESY supported data collection. ESY analyzed the data. ESY, SKK, and KHY drafted the original paper. All authors have reviewed and edited the paper. KHY supervised the study.

Corresponding author

Correspondence to Keon Hee Yoo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yi, E.S., Kim, S.K., Ju, H.Y. et al. Allogeneic hematopoietic cell transplantation in patients with juvenile myelomonocytic leukemia in Korea: a report of the Korean Pediatric Hematology-Oncology Group. Bone Marrow Transplant (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI:


Quick links