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

Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment

Bone Marrow Transplantation volume 48, pages 926–931 (2013)Cite this article

Subjects

Abstract

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (⩾12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (⩾13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (⩾38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66–88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Kishi Y, Kami M, Miyakoshi S, Kanda Y, Murashige N, Teshima T et al. Early immune reaction after reduced-intensity cord-blood transplantation for adult patients. Transplantation 2005; 80: 34–40.

    Article  PubMed  Google Scholar 

  2. Patel KJ, Rice RD, Hawke R, Abboud M, Heller G, Scaradavou A et al. Pre-engraftment syndrome after double-unit cord blood transplantation: a distinct syndrome not associated with acute graft-versus-host disease. Biol Blood Marrow Transplant 2010; 16: 435–440.

    Article  PubMed  Google Scholar 

  3. Uchida N, Wake A, Nakano N, Ishiwata K, Takagi S, Tsuji M et al. Mycophenolate and tacrolimus for graft-versus-host disease prophylaxis for elderly after cord blood transplantation: a matched pair comparison with tacrolimus alone. Transplantation 2011; 92: 366–371.

    Article  CAS  PubMed  Google Scholar 

  4. Narimatsu H, Terakura S, Matsuo K, Oba T, Uchida T, Iida H et al. Short-term methotrexate could reduce early immune reactions and improve outcomes in umbilical cord blood transplantation for adults. Bone Marrow Transplant 2007; 39: 31–39.

    Article  CAS  PubMed  Google Scholar 

  5. Frangoul H, Wang L, Harrell FE, Ho R, Domm J . Preengraftment syndrome after unrelated cord blood transplant is a strong predictor of acute and chronic graft-versus-host disease. Biol Blood Marrow Transplant 2009; 15: 1485–1488.

    Article  CAS  PubMed  Google Scholar 

  6. 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  PubMed  Google Scholar 

  7. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  8. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  9. Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000; 96: 2062–2068.

    CAS  PubMed  Google Scholar 

  10. Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303–2314.

    CAS  PubMed  Google Scholar 

  11. Hiraoka A, Ohashi Y, Okamoto S, Moriyama Y, Nagao T, Kodera Y et al. Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 28: 181–185.

    Article  CAS  PubMed  Google Scholar 

  12. Yanada M, Emi N, Naoe T, Sakamaki H, Takahashi S, Hirabayashi N et al. Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan. Bone Marrow Transplant 2004; 34: 331–337.

    Article  CAS  PubMed  Google Scholar 

  13. Inamoto Y, Flowers ME, Appelbaum FR, Carpenter PA, Deeg HJ, Furlong T et al. A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation with mobilized blood cells. Biol Blood Marrow Transplant 2011; 17: 1088–1092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Spitzer TR . Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27: 893–898.

    Article  CAS  PubMed  Google Scholar 

  15. Maiolino A, Biasoli I, Lima J, Portugal AC, Pulcheri W, Nucci M . Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transplant 2003; 31: 393–397.

    Article  CAS  PubMed  Google Scholar 

  16. Sullivan KM, Deeg HJ, Sanders J, Klosterman A, Amos D, Shulman H et al. Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation. Blood 1986; 67: 1172–1175.

    CAS  PubMed  Google Scholar 

  17. Saliba RM, de Lima M, Giralt S, Andersson B, Khouri IF, Hosing C et al. Hyperacute GVHD: risk factors, outcomes, and clinical implications. Blood 2007; 109: 2751–2758.

    CAS  PubMed  Google Scholar 

  18. Morita-Hoshi Y, Mori SI, Soeda A, Wakeda T, Ohsaki Y, Shiwa M et al. Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS. Bone Marrow Transplant 2010; 45: 1594–1601.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

JK is a Research Fellow of the Japan Society for the Promotion of Science. This work was supported in part by National Cancer Institute (NIH) 5P01-CA047741-18 (MEH and NJC) and a Grant-in-Aid for JSPS Fellows (JK).

Author information

Authors and Affiliations

  1. Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    J Kanda, L Kaynar, D A Rizzieri, G D Long, K M Sullivan, C Gasparetto, J P Chute, A Morris, S Winkel, J McPherson, N J Chao & M E Horwitz

  2. Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

    J Kanda & Y Kanda

  3. Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    L Kaynar

  4. Division of Pediatrics, Duke University Medical Center, Durham, NC, USA

    V K Prasad, S H Parikh & J Kurtzberg

  5. Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, NC, USA

    L Lan & T Shen

Authors
  1. J Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Kaynar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V K Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S H Parikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D A Rizzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G D Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K M Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Gasparetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J P Chute
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S Winkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. J McPherson
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J Kurtzberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. N J Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. M E Horwitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M E Horwitz.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanda, J., Kaynar, L., Kanda, Y. et al. Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment. Bone Marrow Transplant 48, 926–931 (2013). https://doi.org/10.1038/bmt.2012.279

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.279

Keywords

This article is cited by

Search

Advanced search

Quick links