Skip to main content

Advertisement

SpringerLink
Log in

Unrelated umbilical cord blood transplantation with low-dose anti-thymocyte globulin for children with severe aplastic anemia: A case series

  • Research
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Objective

This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed with severe aplastic anemia (SAA).

Methods

This retrospective case series study was conducted involving pediatric SAA patients treated at the Capital Institute of Pediatrics from January 2020 to February 2023. All patients underwent a reduced-intensity conditioning (RIC) regimen alongside low-dose ATG.

Results

The study comprised nine patients (five males) with a median age of 5 years (range: 1.7 to 7 years). The median follow-up duration was 799 days (range: 367 to 1481 days), during which all patients survived. The median time interval from diagnosis to transplantation was 3 months (range: 1 to 9 months). The median dosage of ATG administered was 5 mg/kg (range: 2.5 to 7.5 mg/kg). The median durations for granulocyte and platelet engraftment were 15 days (range: 12 to 23 days) and 26 days (range: 12 to 41 days), respectively. Three patients experienced grade 2–4 acute graft-versus-host disease (aGVHD). Epstein-Barr virus (EBV) reactivation was observed in three patients, while cytomegalovirus (CMV) reactivation occurred in seven patients, with no cases of CMV disease or post-transplant lymphoproliferative disorder (PTLD). One patient experienced recurrence 15 months after transplantation due to influenza A infection.

Conclusion

These findings indicate that SAA patients may attain a favorable prognosis following UCBT with a RIC regimen combined with low-dose ATG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article.

Abbreviations

AA:

Aplastic anemia

SAA:

Severe AA

IST:

Immunosuppressive therapy

ATG/ALG:

Anti-thymocyte/lymphocyte globulin

CsA:

Cyclosporin A

TPO-RA:

Thrombopoietin receptor agonists

UCBT:

Umbilical cord blood transplantation

HLA:

Human leukocyte antigen

GF:

Graft failure

OS:

Overall survival

RIC:

Reduced-intensity conditioning

CB:

Cord blood

TNCs:

Total nucleated cells

FLU:

Fludarabine

CY:

Cyclophosphamide

rATG:

Rabbit ATG

GVHD:

Graft-versus-host disease

aGVHD:

Acute GVHD

CMV:

Cytomegalovirus

cGVHD:

Chronic GVHD

MMF:

Mycophenolate mofetil

DFS:

Disease-free survival

EBV:

Epstein-Barr virus

FDC:

Full donor chimerism

VSAA:

Very severe AA

PTLD:

Post-transplant lymphoproliferative disorder

NRM:

Non-relapse mortality

References

  1. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC (2016) British Society for Standards in H Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 172:187–207. https://doi.org/10.1111/bjh.13853

  2. DeZern AE, Guinan EC (2014) Aplastic anemia in adolescents and young adults. Acta Haematol 132:331–339. https://doi.org/10.1159/000360209

    Article  CAS  PubMed  Google Scholar 

  3. Hartung HD, Olson TS, Bessler M (2013) Acquired aplastic anemia in children. Pediatr Clin North Am 60:1311–1336. https://doi.org/10.1016/j.pcl.2013.08.011

    Article  PubMed  PubMed Central  Google Scholar 

  4. Valdez JM, Scheinberg P, Young NS, Walsh TJ (2009) Infections in patients with aplastic anemia. Semin Hematol 46:269–276. https://doi.org/10.1053/j.seminhematol.2009.03.008

    Article  PubMed  Google Scholar 

  5. Peffault de Latour R, Purtill D, Ruggeri A, Sanz G, Michel G, Gandemer V, Maury S, Kurtzberg J, Bonfim C, Aljurf M, Gluckman E, Socie G, Passweg J, Rocha V (2011) Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation. Biol Blood Marrow Transpl 17:78–85. https://doi.org/10.1016/j.bbmt.2010.06.011

    Article  Google Scholar 

  6. Peffault de Latour R, Chevret S, Jubert C, Sirvent A, Galambrun C, Ruggeri A, Gandemer V, Cornillon J, Rialland F, Dalle JH, Forcade E, Bruno B, Paillard C, Rorlich PS, Salmon A, Furst S, Sicre de Fontbrune F, Rubio MT, Bay JO, Mohty M, Larghero J, Gluckman E, Socie G, Francophone Society of Bone Marrow T, Cellular T (2018) Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study. Blood 132:750–754. https://doi.org/10.1182/blood-2018-01-829630

  7. Yoshimi A, Kojima S, Taniguchi S, Hara J, Matsui T, Takahashi Y, Azuma H, Kato K, Nagamura-Inoue T, Kai S, Kato S, Japan Cord Blood Bank N (2008) Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transpl 14:1057–1063. https://doi.org/10.1016/j.bbmt.2008.07.003

    Article  CAS  Google Scholar 

  8. Kojima S, Nakao S, Tomonaga M, Hows J, Marsh J, Gerard S, Bacigalupo A, Mizoguchi H (2000) Consensus Conference on the Treatment of Aplastic Anemia. Int J Hematol 72:118–123

  9. Jaing TH, Huang IA, Chen SH, Yang CP, Liang DC, Hung IJ (2011) Cord blood transplantation in children with relapsed or refractory severe aplastic anemia. J Pediatr Hematol Oncol 33:18–21. https://doi.org/10.1097/MPH.0b013e3181f46e51

    Article  PubMed  Google Scholar 

  10. Ochi T, Onishi Y, Nasu K, Onodera K, Kobayashi M, Ichikawa S, Fujiwara T, Fukuhara N, Yamada-Fujiwara M, Harigae H (2019) Umbilical cord blood transplantation using reduced-intensity conditioning without antithymocyte globulin in adult patients with severe aplastic Anemia. Biol Blood Marrow Transpl 25:e55–e59. https://doi.org/10.1016/j.bbmt.2018.09.039

    Article  Google Scholar 

  11. Tong J, Xuan L, Sun Y, Huang D, Liu H, Zheng C, Zhu X, Tang B, Song K, Zhang X, Zhang L, Yao W, Lin D, Liu Q, Sun Z (2017) Umbilical cord blood transplantation without Antithymocyte Globulin results in similar survival but Better Quality of Life Compared with unrelated peripheral blood stem cell transplantation for the treatment of Acute Leukemia-A Retrospective Study in China. Biol Blood Marrow Transpl 23:1541–1548. https://doi.org/10.1016/j.bbmt.2017.05.004

    Article  Google Scholar 

  12. de Koning C, Admiraal R, Nierkens S, Boelens JJ (2017) Immune reconstitution and outcomes after conditioning with anti-thymocyte-globulin in unrelated cord blood transplantation; the good, the bad, and the ugly. Stem Cell Investig 4:38. https://doi.org/10.21037/sci.2017.05.02

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Qin BZ, Zhang C, Zhang R, Wang L (2020) Role of antithymocyte globulin in patients with hematologic diseases undergoing umbilical cord blood transplantation: a systematic review and meta-analysis. Clin Transpl 34:e13876. https://doi.org/10.1111/ctr.13876

    Article  CAS  Google Scholar 

  14. Liu HL, Sun ZM, Geng LQ, Wang XB, Ding KY, Tang BI, Tong J, Wang ZY (2012) Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival. Bone Marrow Transpl 47:1186–1190. https://doi.org/10.1038/bmt.2011.251

    Article  CAS  Google Scholar 

  15. Red Blood Cell Disease Group CSoHCMA (2022) [Guidelines for the diagnosis and management of aplastic anemia in China (2022)]. Zhonghua Xue Ye Xue Za Zhi 43:881–888. https://doi.org/10.3760/cma.j.issn.0253-2727.2022.11.001

    Article  Google Scholar 

  16. Incidence of aplastic anemia: the relevance of diagnostic criteria. Int Agranulocytosis Aplastic Anemia Study (1987) Blood 70:1718–1721

  17. P D, W D, M P, K HG, B P, H J, T ED (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl 15:825–828

  18. Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transpl 9:215–233. https://doi.org/10.1053/bbmt.2003.50026

    Article  CAS  Google Scholar 

  19. Garderet L, Dulphy N, Douay C, Chalumeau N, Schaeffer V, Zilber MT, Lim A, Even J, Mooney N, Gelin C, Gluckman E, Charron D, Toubert A (1998) The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood 91:340–346

    Article  CAS  PubMed  Google Scholar 

  20. Long GD, Laughlin M, Madan B, Kurtzberg J, Gasparetto C, Morris A, Rizzieri D, Smith C, Vredenburgh J, Halperin EC, Broadwater G, Niedzwiecki D, Chao NJ (2003) Unrelated umbilical cord blood transplantation in adult patients. Biol Blood Marrow Transpl 9:772–780. https://doi.org/10.1016/j.bbmt.2003.08.007

    Article  Google Scholar 

  21. Lindemans CA, Chiesa R, Amrolia PJ, Rao K, Nikolajeva O, de Wildt A, Gerhardt CE, Gilmour KC, Veys MBB, Boelens P JJ (2014) Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood 123:126–132. https://doi.org/10.1182/blood-2013-05-502385

    Article  CAS  PubMed  Google Scholar 

  22. Pascal L, Tucunduva L, Ruggeri A, Blaise D, Ceballos P, Chevallier P, Cornelissen J, Maillard N, Tabrizi R, Petersen E, Linkesch W, Sengeloev H, Kenzey C, Pagliuca A, Holler E, Einsele H, Gluckman E, Rocha V, Yakoub-Agha I, Eurocord, the European Society for B, Marrow T (2015) Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation. Blood 126:1027–1032. https://doi.org/10.1182/blood-2014-09-599241

  23. Alshaibani A, Dufour C, Risitano A, de Latour R, Aljurf M (2022) Hepatitis-Associated Aplastic Anemia. Hematol Oncol Stem Cell Ther 15:8–12. https://doi.org/10.1016/j.hemonc.2020.10.001

    Article  CAS  PubMed  Google Scholar 

  24. Baron F, Mohty M, Blaise D, Socie G, Labopin M, Esteve J, Ciceri F, Giebel S, Gorin NC, Savani BN, Schmid C, Nagler A (2017) Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and marrow transplantation. Haematologica 102:224–234. https://doi.org/10.3324/haematol.2016.148510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Hematology, Children’s Hospital Capital Institute of Pediatrics, Beijing, 100020, China

    Mengze Hu, Junhui Li, Rong Liu, Zhaoxia Zhang, Shunqiao Feng, Dixiao Zhong, Ruihong Tang & Litian Xuan

Authors
  1. Mengze Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junhui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhaoxia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shunqiao Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dixiao Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruihong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Litian Xuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Mengze Hu conducted the studies, participated in data collection, performed statistical analysis, and drafted the manuscript. Rong Liu contributed to the study design and revised the manuscript. Junhui Li, Zhaoxia Zhang, Shunqiao Feng, Dixiao Zhong, Ruihong Tang, and Litian Xuan were involved in patient management, data acquisition, and interpretation. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Rong Liu.

Ethics declarations

Competing interests

The authors affirm that they have no known conflicting financial interests or personal relationships that might have influenced the work presented in this paper.

Ethical statement

The Medical Ethics Committee of the Capital Institute of Pediatrics granted approval for the study (SHERLLM2023055). Given the retrospective nature of the study, the need for individual informed consent was waived by the committee.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) 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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, M., Li, J., Liu, R. et al. Unrelated umbilical cord blood transplantation with low-dose anti-thymocyte globulin for children with severe aplastic anemia: A case series. Ann Hematol 103, 2103–2111 (2024). https://doi.org/10.1007/s00277-024-05756-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-024-05756-2

Keywords

Search

Navigation