Skip to main content

Advertisement

SpringerLink
Log in

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation

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

Abstract

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT—304 males (68%) and 140 females (32%)—with a median age of 3.3 years (1.8–6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

For data sharing, please contact the corresponding author (douying523@aliyun.com).

References

  1. Balassa K, Danby R, Rocha V (2019) Haematopoietic stem cell transplants: principles and indications. Br J Hosp Med (Lond) 80(1):33–39. https://doi.org/10.12968/hmed.2019.80.1.33

    Article  PubMed  Google Scholar 

  2. Barriga F, Ramírez P, Wietstruck A, Rojas N (2012) Hematopoietic stem cell transplantation: clinical use and perspectives. Biol Res 45(3):307–316. https://doi.org/10.4067/S0716-97602012000300012

    Article  CAS  PubMed  Google Scholar 

  3. Zhao Y, He R, Oerther S, Zhou W, Vosough M, Hassan M (2022) Cardiovascular complications in hematopoietic stem cell transplanted patients. J Pers Med 12(11):1797. https://doi.org/10.3390/jpm12111797

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bhatia S (2011) Long-term health impacts of hematopoietic stem cell transplantation inform recommendations for follow-up. Expert Rev Hematol 4(4):437–454. https://doi.org/10.1586/ehm.11.39

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ohmoto A, Fuji S (2021) Cardiac complications associated with hematopoietic stem-cell transplantation. Bone Marrow Transplant 56(11):2637–2643. https://doi.org/10.1038/s41409-021-01427-2

    Article  PubMed  Google Scholar 

  6. Buja LM, Ferrans VJ, Graw RG Jr (1976) Cardiac pathologic findings in patients treated with bone marrow transplantation. Hum Pathol 7(1):17–45. https://doi.org/10.1016/s0046-8177(76)80004-4

    Article  CAS  PubMed  Google Scholar 

  7. Rotz SJ, Ryan TD, Jodele S, Jefferies JL, Lane A, Pate A, Hirsch R, Hlavaty J, Levesque AE, Taylor MD, Cash M, Myers KC, El-Bietar JA, Davies SM, Dandoy CE (2017) The injured heart: early cardiac effects of hematopoietic stem cell transplantation in children and young adults. Bone Marrow Transplant 52(8):1171–1179. https://doi.org/10.1038/bmt.2017.62

    Article  CAS  PubMed  Google Scholar 

  8. Rotz SJ, Ryan TD, Hayek SS (2021) Cardiovascular disease and its management in children and adults undergoing hematopoietic stem cell transplantation. J Thromb Thrombolysis 51(4):854–869. https://doi.org/10.1007/s11239-020-02344-9

    Article  PubMed  Google Scholar 

  9. Duléry R, Mohty R, Labopin M, Sestili S, Malard F, Brissot E, Battipaglia G, Médiavilla C, Banet A, Van de Wyngaert Z, Paviglianiti A, Belhocine R, Isnard F, Lapusan S, Adaeva R, Vekhoff A, Ledraa T, Legrand O, Cohen A, Bonnin A, Ederhy S, Mohty M (2021) Early Cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation. JACC CardioOncol 3(2):250–259. https://doi.org/10.1016/j.jaccao.2021.02.011

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yeh J, Whited L, Saliba RM, Rondon G, Banchs J, Shpall E, Champlin R, Popat U (2021) Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Adv 5(24):5599–5607. https://doi.org/10.1182/bloodadvances.2021004846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Duncan CN, Brazauskas R, Huang J, Shaw BE, Majhail NS, Savani BN, Flowers MED, Battiwalla M, Beebe K, Dietz AC, Dvorak CC, Giller R, Jacobsohn DA, Kletzel M, Martin PL, Nemecek ER, Nuechterlein B, Talano JA, Pulsipher MA, Baker KS (2018) Late cardiovascular morbidity and mortality following pediatric allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 53(10):1278–1287. https://doi.org/10.1038/s41409-018-0155-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Johansson T, Partanen J, Saavalainen P (2022) HLA allele-specific expression: methods, disease associations, and relevance in hematopoietic stem cell transplantation. Front Immunol 13:1007425. https://doi.org/10.3389/fimmu.2022.1007425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events, Version 4.0 (version 4.03) (2009). Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf/. Accessed 28 Nov 2020

  14. Hertenstein B, Stefanic M, Schmeiser T, Scholz M, Göller V, Clausen M, Bunjes D, Wiesneth M, Novotny J, Kochs M (1994) Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant. J Clin Oncol 12(5):998–1004. https://doi.org/10.1200/JCO.1994.12.5.998

    Article  CAS  PubMed  Google Scholar 

  15. Pérez-Valencia AI, Cascos E, Carbonell-Ordeig S, Charry P, Gómez-Hernando M, Rodríguez-Lobato LG, Suárez-Lledó M, Martínez-Cibrian N, Antelo MG, Solano MT, Arcarons J, Nomdedeu M, Cid J, Lozano M, Díaz-Ricart M, Rosiñol L, Esteve J, Urbano-Ispizua Á, Carreras E, Martínez C, Fernández-Avilés F, Rovira M, Salas MQ (2023) Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant. Blood Adv 7(10):2018–2031. https://doi.org/10.1182/bloodadvances.2022008792

    Article  CAS  PubMed  Google Scholar 

  16. Alblooshi R, Kanfar S, Lord B, Atenafu EG, Michelis FV, Pasic I, Gerbitz A, Al-Shaibani Z, Viswabandya A, Kim DDH, Lam W, Law A, Mattsson J, Kumar R, Lipton JH (2021) Clinical prevalence and outcome of cardiovascular events in the first 100 days postallogeneic hematopoietic stem cell transplant. Eur J Haematol 106(1):32–39. https://doi.org/10.1111/ejh.13482

    Article  CAS  PubMed  Google Scholar 

  17. Armenian SH, Yang D, Teh JB, Atencio LC, Gonzales A, Wong FL, Leisenring WM, Forman SJ, Nakamura R, Chow EJ (2018) Prediction of cardiovascular disease among hematopoietic cell transplantation survivors. Blood Adv 2(14):1756–1764. https://doi.org/10.1182/bloodadvances.2018019117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Leger KJ, Baker KS, Cushing-Haugen KL, Flowers MED, Leisenring WM, Martin PJ, Mendoza JA, Reding KW, Syrjala KL, Lee SJ, Chow EJ (2018) Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation. Cancer 124(7):1507–1515. https://doi.org/10.1002/cncr.31227

    Article  PubMed  Google Scholar 

  19. Tichelli A, Bucher C, Rovó A, Stussi G, Stern M, Paulussen M, Halter J, Meyer-Monard S, Heim D, Tsakiris DA, Biedermann B, Passweg JR, Gratwohl A (2007) Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood 110(9):3463–3471. https://doi.org/10.1182/blood-2006-10-054080

    Article  CAS  PubMed  Google Scholar 

  20. Uderzo C, Pillon M, Corti P, Tridello G, Tana F, Zintl F, Nysom K, Galambrun C, Fagioli F, Varotto S, Messina C, Verdeguer A, Urban C, Faraci M, Dini G, Fedeli S, Tichelli A, Rovelli A, Socié G (2007) Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties. Bone Marrow Transplant 39(11):667–675. https://doi.org/10.1038/sj.bmt.1705652

    Article  CAS  PubMed  Google Scholar 

  21. Kurauchi K, Nishikawa T, Miyahara E, Okamoto Y, Kawano Y (2017) Role of metabolites of cyclophosphamide in cardiotoxicity. BMC Res Notes 10(1):406. https://doi.org/10.1186/s13104-017-2726-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tong K, Meng Y, Zhang L, Lei X, Guan X, Xiao L, Yu J, Dou Y (2023) Retrospective study of risk factors for pericardial effusion after haematopoietic stem cell transplantation in children. Hematology 28(1):2245259. https://doi.org/10.1080/16078454.2023.2245259

    Article  CAS  PubMed  Google Scholar 

  23. Anasetti C (2008) What are the most important donor and recipient factors affecting the outcome of related and unrelated allogeneic transplantation? Best Pract Res Clin Haematol 21(4):691–697. https://doi.org/10.1016/j.beha.2008.10.002

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tinianow A, Gay JC, Bearl DW, Connelly JA, Godown J, Kitko CL (2020) Pericardial effusion following hematopoietic stem cell transplantation in children: Incidence, risk factors, and outcomes. Pediatr Transplant 24(5):e13748. https://doi.org/10.1111/petr.13748

    Article  CAS  PubMed  Google Scholar 

  25. Neier M, Jin Z, Kleinman C, Baldinger L, Bhatia M, Silver E, van de Ven C, Morris E, Satwani P, George D, Garvin J, Bradley MB, Schwartz J, Cairo MS (2011) Pericardial effusion post-SCT in pediatric recipients with signs and/or symptoms of cardiac disease. Bone Marrow Transplant 46(4):529–538. https://doi.org/10.1038/bmt.2010.149

    Article  CAS  PubMed  Google Scholar 

  26. Sommer A, Twig G (2018) The impact of childhood and adolescent obesity on cardiovascular risk in adulthood: a systematic review. Curr Diab Rep 18(10):91. https://doi.org/10.1007/s11892-018-1062-9

    Article  PubMed  Google Scholar 

  27. Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH (2007) Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr 150(1):12-17.e2. https://doi.org/10.1016/j.jpeds.2006.08.042

    Article  PubMed  Google Scholar 

  28. Aldoss O, Gruenstein DH, Bass JL, Steinberger J, Zhang Y, Defor TE, Tolar J, Verneris MR, Orchard PJ (2013) Pericardial effusion after pediatric hematopoietic cell transplant. Pediatr Transplant 17(3):294–299. https://doi.org/10.1111/petr.12062

    Article  CAS  PubMed  Google Scholar 

  29. Yanagisawa R, Ishii E, Motoki N, Yamazaki S, Morita D, Sakashita K, Shiohara M, Tanaka M, Hidaka Y, Kubota N, Hidaka E, Ogiso Y, Nakamura T, Yasukochi S (2015) Pretransplant-corrected QT dispersion as a predictor of pericardial effusion after pediatric hematopoietic stem cell transplantation. Transpl Int 28(5):565–574. https://doi.org/10.1111/tri.12532

    Article  PubMed  Google Scholar 

  30. Liu YC, Gau JP, Hong YC, Yu YB, Hsiao LT, Liu JH, Chiou TJ, Chen PM, Tzeng CH (2012) Large pericardial effusion as a life-threatening complication after hematopoietic stem cell transplantation-association with chronic GVHD in late-onset adult patients. Ann Hematol 91(12):1953–1958. https://doi.org/10.1007/s00277-012-1541-z

    Article  PubMed  Google Scholar 

  31. Tonorezos ES, Stillwell EE, Calloway JJ, Glew T, Wessler JD, Rebolledo BJ, Pham A, Steingart RM, Lazarus H, Gale RP, Jakubowski AA, Schaffer WL (2015) Arrhythmias in the setting of hematopoietic cell transplants. Bone Marrow Transplant 50(9):1212–1216. https://doi.org/10.1038/bmt.2015.127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lin CJ, Vader JM, Slade M, DiPersio JF, Westervelt P, Romee R (2017) Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation. Cancer 123(10):1800–1809. https://doi.org/10.1002/cncr.30534

    Article  CAS  PubMed  Google Scholar 

  33. Moriyama S, Fukata M, Hieda M, Yokoyama T, Yoshimoto G, Kusaba H, Nakashima Y, Miyamoto T, Maruyama T, Akashi K (2022) Early-onset cardiac dysfunction following allogeneic haematopoietic stem cell transplantation. Open Heart 9(1):e002007. https://doi.org/10.1136/openhrt-2022-002007

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dandoy CE, Jodele S, Paff Z, Hirsch R, Ryan TD, Jefferies JL, Cash M, Rotz S, Pate A, Taylor MD, El-Bietar J, Myers KC, Wallace G, Nelson A, Grimley M, Pfeiffer T, Lane A, Davies SM, Chima RS (2017) Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer 64(10). https://doi.org/10.1002/pbc.26513

  35. Diamond M, Ruiz-Mesa C, Corrales-Medina FF, Tamariz LJ, Ziga E, Swaminathan S (2018) Incidence and outcome of pericardial effusion in pediatric patients after hematopoietic stem cell transplant: a single-institution experience. J Pediatr Hematol Oncol 40(2):132–136. https://doi.org/10.1097/MPH.0000000000000974

    Article  PubMed  Google Scholar 

  36. Jaing TH, Chen SH, Wen YC, Chang TY, Tsai DY, Chung HT, Tsay PK (2017) Factors affecting survival in children with pericardial effusion after hematopoietic stem cell transplantation. Cell Transplant 26(11):1792–1797. https://doi.org/10.1177/0963689717727285

    Article  PubMed  Google Scholar 

  37. Umeda K, Imai K, Yanagimachi M, Yabe H, Kobayashi M, Takahashi Y, Kajiwara M, Yoshida N, Cho Y, Inoue M, Hashii Y, Atsuta Y, Morio T, Inherited Disease Working Group of the Japan Society for Hematopoietic Cell Transplantation (2020) Impact of graft-versus-host disease on the clinical outcome of allogeneic hematopoietic stem cell transplantation for non-malignant diseases. Int J Hematol 111(6):869–876. https://doi.org/10.1007/s12185-020-02839-4

    Article  CAS  PubMed  Google Scholar 

  38. Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, Santarone S, Gülbas Z, Blaise D, Messina G, Ghavamzadeh A, Malard F, Bruno B, Diez-Martin JL, Koc Y, Ciceri F, Mohty M, Nagler A (2017) Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica 102(2):401–410. https://doi.org/10.3324/haematol.2016.151779

    Article  PubMed  PubMed Central  Google Scholar 

  39. Soltermann Y, Heim D, Medinger M, Baldomero H, Halter JP, Gerull S, Arranto C, Passweg JR, Kleber M (2019) Reduced dose of post-transplantation cyclophosphamide compared to ATG for graft-versus-host disease prophylaxis in recipients of mismatched unrelated donor hematopoietic cell transplantation: a single-center study. Ann Hematol 98(6):1485–1493. https://doi.org/10.1007/s00277-019-03673-3

    Article  CAS  PubMed  Google Scholar 

  40. Zu Y, Zhou J, Fu Y, Fang B, Liu X, Zhang Y, Yu F, Zuo W, Zhou H, Gui R, Li Z, Liu Y, Zhao H, Zhang C, Song Y (2021) Feasibility of reduced-dose posttransplant cyclophosphamide and cotransplantation of peripheral blood stem cells and umbilical cord-derived mesenchymal stem cells for SAA. Sci Rep 11(1):253. https://doi.org/10.1038/s41598-020-80531-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the patients and the nursing and support staff in the HSCT program.

Funding

This work was supported by the Program for Youth Innovation in Future Medicine, Chongqing Medical University (grant number W0132) and the Natural Science Foundation of Chongqing, China (CSTB2023NSCQ-MSX0212).

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, National Clinical Research Center for Child Health and Disorders Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Ke Tong, Yan Meng, Luying Zhang, Xiaoying Lei, Qihui Liu, Xianmin Guan, Jie Yu & Ying Dou

Authors
  1. Ke Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoying Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qihui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xianmin Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ying Dou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.D. designed the research and edited the manuscript. Y.M., L.Z., X.L., Q.L., X.G. and J.Y. provided detailed materials for this manuscript. K.T. collected and analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Ying Dou.

Ethics declarations

Consent for publication

All authors have read the manuscript and made the decision to submit it for publication. The corresponding author had final responsibility for the decision to submit this manuscript for publication.

Ethics approval

All procedures were performed according to the ethical standards of the institutional and national research committees and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the institutional review board.

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.

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

Tong, K., Meng, Y., Zhang, L. et al. Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05787-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00277-024-05787-9

Keywords

Search

Navigation