Skip to main content

Advertisement

SpringerLink
Log in

Chronic graft-versus-host disease in children and adolescents with thalassemia after hematopoietic stem cell transplantation

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Data on chronic graft-versus-host disease (cGVHD) in patients with thalassemia after hematopoietic stem cell transplantation (HSCT) have not been specifically explored. The present study aimed to determine the incidence and clinical manifestations of cGVHD in children and adolescents with thalassemia who underwent HSCT and to compare healthcare utilization and medical cost between patients with and without cGVHD. We retrospectively analyzed the presentations, treatments, and outcomes of historical cGVHD (Seattle criteria), post-transplant admissions and direct medical cost for HSCT patients (n = 66). We used the 2014 NIH consensus criteria to reclassify the diagnosis of cGVHD (NIH cGVHD). Among 28 historical cGVHD patients, 13 (46.4%) fulfilled the NIH criteria. Reasons why the NIH criteria were unmet were reclassification as late acute GVHD and presence of distinctive signs without confirmatory tests. At 2 years after HSCT, the cumulative incidence of NIH cGVHD was 21.67% (95% CI, 12.31–32.74%). Lung cGVHD was associated with inferior survival with a hazard ratio of 13.6 (95% CI, 1.42–131.48). Patients with historical cGVHD had significantly increased frequency of inpatient admissions and medical cost. In conclusion, cGVHD was common in children with thalassemia receiving HSCT. Patients with cGVHD required prolonged immunosuppressive treatment and incurred high medical expenses.

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

References

  1. Hongeng S, Pakakasama S, Chuansumrit A, Sirachainan N, Kitpoka P, Udomsubpayakul U, et al. Outcomes of transplantation with related- and unrelated-donor stem cells in children with severe thalassemia. Biol Blood Marrow Transplant. 2006;12:683–7.

    Article  Google Scholar 

  2. Sun L, Wang N, Chen Y, Tang L, Xing C, Lu N, et al. Unrelated donor peripheral blood stem cell transplantation for patients with β-thalassemia major based on a novel conditioning regimen. Biol Blood Marrow Transplant. 2019;25:1592–6.

    Article  Google Scholar 

  3. Anurathapan U, Pakakasama S, Mekjaruskul P, Sirachainan N, Songdej D, Chuansumrit A, et al. Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification. Biol Blood Marrow Transplant. 2014;20:2066–71.

    Article  Google Scholar 

  4. Anurathapan U, Hongeng S, Pakakasama S, Songdej D, Sirachainan N, Pongphitcha P, et al. Hematopoietic stem cell transplantation for severe thalassemia patients from haploidentical donors using a novel conditioning regimen. Biol Blood Marrow Transplant. 2020;26:1106–12.

    Article  CAS  Google Scholar 

  5. Bolanos-Meade J, Cooke KR, Gamper CJ, Ali SA, Ambinder RF, Borrello IM, et al. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019;6:e183–93.

    Article  Google Scholar 

  6. Lee SJ, Klein JP, Barrett J, Ringden O, Antin JH, Cahn JY, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–14.

    Article  CAS  Google Scholar 

  7. Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. N Engl J Med. 1999;341:14–21.

    Article  CAS  Google Scholar 

  8. Li X, Gao Q, Feng Y, Zhang X. Developing role of B cells in the pathogenesis and treatment of chronic GVHD. Br J Haematol. 2019;184:323–36.

    Article  Google Scholar 

  9. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  Google Scholar 

  10. Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:215–33.

    Article  CAS  Google Scholar 

  11. Lee SJ. Classification systems for chronic graft-versus-host disease. Blood. 2017;129:30–7.

    Article  CAS  Google Scholar 

  12. 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 Transplant. 2005;11:945–55.

    Article  Google Scholar 

  13. Cho BS, Min CK, Eom KS, Kim YJ, Kim HJ, Lee S, et al. Feasibility of NIH consensus criteria for chronic graft-versus-host-disease. Leukemia. 2009;23:78–84.

    Article  Google Scholar 

  14. Inagaki J, Moritake H, Nishikawa T, Hyakuna N, Okada M, Suenobu S, et al. Long-term morbidity and mortality in children with chronic graft-versus-host disease classified by National Institutes of Health consensus criteria after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1973–80.

    Article  Google Scholar 

  15. Inamoto Y, Jagasia M, Wood WA, Pidala J, Palmer J, Khera N, et al. Investigator feedback about the 2005 NIH diagnostic and scoring criteria for chronic GVHD. Bone Marrow Transplant. 2014;49:532–8.

    Article  Google Scholar 

  16. 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 Transplant. 2014;2015(21):389–401.

    Google Scholar 

  17. Ito R, Inamoto Y, Inoue Y, Ito A, Tanaka T, Fuji S, et al. Characterization of late acute and chronic graft-versus-host disease according to the 2014 National Institutes of Health consensus criteria in Japanese patients. Biol Blood Marrow Transplant. 2019;25:293–300.

    Article  Google Scholar 

  18. Kerep AZ, Broome J, Pirsl F, Curtis LM, Steinberg SM, Mitchell SA, et al. Impact of the 2014 NIH chronic graft-versus-host disease scoring criteria modifications assessed in a large cohort of severely affected patients. Bone Marrow Transplant. 2019;54:76–84.

    Article  Google Scholar 

  19. Arora M, Cutler CS, Jagasia MH, Pidala J, Chai X, Martin PJ, et al. Late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:449–55.

    Article  Google Scholar 

  20. Cuvelier GDE, Nemecek ER, Washlstrom JT, Kitko CL, Lewis VA, Schechter T, et al. Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria. Blood. 2019;134:304–16.

    Article  CAS  Google Scholar 

  21. John MJ, Mathew A, Philip CC, Singh S, Tanuja T, Kakkar N. Unrelated and related donor transplantation for beta-thalassemia major: a single-center experience from India. Pediatr Int. 2018;22:e13209.

    Google Scholar 

  22. Swaminathan VV, Uppuluri R, Patel S, Ravichandran N, Ramanan KM, Vaidhyanathan L, et al. Matched family versus alternative donor hematopoietic stem cell transplantation for patients with thalassemia major: experience from a tertiary referral center in south India. Biol Blood Marrow Transplant. 2020;26:1326–31.

    Article  CAS  Google Scholar 

  23. Au BKC, Au MA, Chien JW. Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17:1072–8.

    Article  Google Scholar 

  24. Vieira AG, Funke VAM, Nunes EC, Pasquini R. Bronchiolitis obliterans in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant. 2014;49:812–7.

    Article  CAS  Google Scholar 

  25. Esperou H, Brunot A, Roudot-Thoraval F, Buzyn A, Dhedin N, Rio B, et al. Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective, multicenter. French study Transplantation. 2004;12:1854–8.

    Google Scholar 

  26. Ricci A, Jin Z, Bourgeois W, Broglie L, Bhatia M, Davis L, et al. Financial impact of post-transplant complications among children undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2020;55:384–92.

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank Alison Sherwin, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Oranooj Lertkovit, Usanarat Anurathapan, Suradej Hongeng & Samart Pakakasama

  2. Ramathibodi Comprehensive Cancer Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Nintita Sripaiboonkit Thokanit

Authors
  1. Oranooj Lertkovit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Usanarat Anurathapan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suradej Hongeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nintita Sripaiboonkit Thokanit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samart Pakakasama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samart Pakakasama.

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.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lertkovit, O., Anurathapan, U., Hongeng, S. et al. Chronic graft-versus-host disease in children and adolescents with thalassemia after hematopoietic stem cell transplantation. Int J Hematol 113, 556–565 (2021). https://doi.org/10.1007/s12185-020-03055-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-020-03055-w

Keywords

Search

Navigation