Skip to main content

Thank you for visiting nature.com. 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.

  • Original Article
  • Published:

Cord Blood Stem Cells

GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome

Bone Marrow Transplantation volume 46, pages 668–675 (2011)Cite this article

Subjects

Abstract

We reviewed our experience in 79 children who had unrelated cord blood transplant (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both traditional and National Institute of Health (NIH) criteria. The cumulative incidence (CI) of acute GVHD (aGVHD, by day +100) was 0.42 for grade II–IV and 0.22 for grade III–IV. The CI of all aGVHD (NIH, that is, no time limit) at 1 year was 0.45 for grade II–IV and 0.32 for grade III–IV. Infused CD34 cell dose (>1 × 105/kg), pretransplant bacterial infection and nonmalignant disorders were risk factors for grade II–IV aGVHD on univariate analysis. Infused CD34 cell dose remained significant on multivariate analysis. At 1 year, the CI of chronic GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH) was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated. Grade II–IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH criteria. We conclude that GVHD after day +100 after UCBT typically carries features of aGVHD. Moreover, and in marked contrast to adult unrelated donor hematopoietic stem cell transplantation, the GVHD observed in this series did not adversely affect survival.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  Google Scholar 

  2. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  Google Scholar 

  3. Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE . Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood 2001; 97: 2957–2961.

    Article  CAS  Google Scholar 

  4. Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC . A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant 2007; 13: 444–453.

    Article  Google Scholar 

  5. Rocha V, Wagner Jr JE, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med 2000; 342: 1846–1854.

    Article  CAS  Google Scholar 

  6. Ballen KK, Haley NR, Kurtzberg J, Lane TA, Lindgren BR, Miller JP et al. Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank. Transfusion 2006; 46: 2063–2070.

    Article  Google Scholar 

  7. Dalle JH, Duval M, Moghrabi A, Wagner E, Vachon MF, Barrette S et al. Results of an unrelated transplant search strategy using partially HLA-mismatched cord blood as an immediate alternative to HLA-matched bone marrow. Bone Marrow Transplant 2004; 33: 605–611.

    Article  CAS  Google Scholar 

  8. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337: 373–381.

    Article  CAS  Google Scholar 

  9. Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335: 157–166.

    Article  CAS  Google Scholar 

  10. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  Google Scholar 

  11. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.

    CAS  Google Scholar 

  12. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  Google Scholar 

  13. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.

    Article  CAS  Google Scholar 

  14. Gluckman E, Rocha V . Donor selection for unrelated cord blood transplants. Curr Opin Immunol 2006; 18: 565–570.

    Article  CAS  Google Scholar 

  15. 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. A J Med 1980; 69: 204–217.

    Article  CAS  Google Scholar 

  16. 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: 945–956.

    Article  Google Scholar 

  17. Jagasia M, Giglia J, Chinratanalab W, Dixon S, Chen H, Frangoul H et al. Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria. Biol Blood Marrow Transplant 2007; 13: 1207–1215.

    Article  Google Scholar 

  18. 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 

  19. Arora M, Nagaraj S, Witte J, DeFor TE, MacMillan M, Burns LJ et al. New classification of chronic GVHD: added clarity from the consensus diagnoses. Bone Marrow Transplant 2009; 43: 149–153.

    Article  CAS  Google Scholar 

  20. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  21. Klein J, Moeschberger M . Survival Analysis: Techniques of Censored and Truncated Data, 2nd edn. Springer: New York, (February 6, 2003).

  22. Klein JP, Gerster M, Andersen PK, Tarima S, Perme MP . SAS and R functions to compute pseudo-values for censored data regression. Comput Methods Programs Biomed 2008; 89: 289–300.

    Article  Google Scholar 

  23. Logan BR, Zhang MJ, Klein JP . Regression models for hazard rates versus cumulative incidence probabilities in hematopoietic cell transplantation data. Biol Blood Marrow Transplant 2006; 12 (1 Suppl 1): 107–112.

    Article  Google Scholar 

  24. Klein JP, Andersen PK . Regression modeling of competing risks data based on pseudovalues of the cumulative incidence function. Biometrics 2005; 61: 223–229.

    Article  Google Scholar 

  25. Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB et al. Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant 2002; 8: 368–376.

    Article  Google Scholar 

  26. Kurtzberg J, Prasad VK, Carter SL, Wagner JE, Baxter-Lowe LA, Wall D et al. Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 2008; 112: 4318–4327.

    Article  CAS  Google Scholar 

  27. Ferrara JL, Reddy P . Pathophysiology of graft-versus-host disease. Semin Hematol 2006; 43: 3–10.

    Article  CAS  Google Scholar 

  28. Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger WI et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100: 415–419.

    Article  CAS  Google Scholar 

  29. Champlin RE, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Cornelissen JJ et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood 2000; 95: 3702–3709.

    CAS  PubMed  Google Scholar 

  30. Fowler DH, Odom J, Steinberg SM, Chow CK, Foley J, Kogan Y et al. Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1150–1160.

    Article  CAS  Google Scholar 

  31. Fowler DH, Gress RE . Th2 and Tc2 cells in the regulation of GVHD, GVL, and graft rejection: considerations for the allogeneic transplantation therapy of leukemia and lymphoma. Leuk Lymphoma 2000; 38: 221–234.

    Article  CAS  Google Scholar 

  32. Arora M, Nagaraj S, Wagner JE, Barker JN, Brunstein CG, Burns LJ et al. Chronic graft-versus-host disease (cGVHD) following unrelated donor hematopoietic stem cell transplantation (HSCT): higher response rate in recipients of unrelated donor (URD) umbilical cord blood (UCB). Biol Blood Marrow Transplant 2007; 13: 1145–1152.

    Article  Google Scholar 

  33. MacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 2009; 113: 2410–2415.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Center for Cancer and Blood Disorders, The Children's Hospital and the University of Colorado Denver School of Medicine, Aurora, CO, USA

    A Alsultan, R H Giller, J Bathurst, E Hild, L Gore, N K Foreman, A Keating & R R Quinones

  2. Department of Pediatrics, Research Institute, The Children's Hospital and the University of Colorado Denver School of Medicine, Aurora, CO, USA

    D Gao

Authors
  1. A Alsultan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R H Giller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Bathurst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Hild
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L Gore
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N K Foreman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R R Quinones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R R Quinones.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alsultan, A., Giller, R., Gao, D. et al. GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome. Bone Marrow Transplant 46, 668–675 (2011). https://doi.org/10.1038/bmt.2010.174

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.174

Keywords

This article is cited by

Search

Advanced search

Quick links