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:

Post-Transplant Events

Hyperbilirubinemia in the early phase after allogeneic HSCT: prognostic significance of the alkaline phosphatase/total bilirubin ratio

Bone Marrow Transplantation volume 48, pages 94–98 (2013)Cite this article

Subjects

Abstract

Hyperbilirubinemia in the early phase after allogeneic hematopoietic SCT (HSCT) is due to various causes. One of the most important causes of hyperbilirubinemia is veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS). However, the prognosis of patients who are clinically diagnosed as SOS varies. We retrospectively evaluated 82 patients who underwent their first allogeneic HSCT. GVHD prophylaxis was a combination of short-term MTX and CsA (n=77) or tacrolimus (n=5). Thirty-three patients developed hyperbilirubinemia, with a bilirubin level of at least 2 mg/dL, within 20 days after HSCT. Of these patients, 24 were diagnosed as VOD/SOS using the modified Seattle criteria. Twenty-six recovered to a bilirubin level of <2 mg/dL. We focused on the serum alkaline phosphatase/total bilirubin ratio (ALP/TB) at the onset of hyperbilirubinemia and found that it significantly predicted the recovery from hyperbilirubinemia. OS was significantly higher in patients with a lower ALP/TB ratio (P=0.00056). In addition, a lower ALP/TB ratio was associated with better survival even in patients who were clinically diagnosed as SOS (P<0.001). The ALP/TB ratio at the onset of hyperbilirubinemia may be a useful predictor for the prognosis of hyperbilirubinemia and SOS early after HSCT.

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
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. McDonald GB . Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology 2010; 51: 1450–1460.

    Article  PubMed  Google Scholar 

  2. Bearman SI . The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85: 3005–3020.

    CAS  PubMed  Google Scholar 

  3. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED . Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology 1984; 4: 116–122.

    Article  CAS  PubMed  Google Scholar 

  4. Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44: 778–783.

    Article  CAS  PubMed  Google Scholar 

  5. Carreras E, Bertz H, Arcese W, Vernant JP, Tomas JF, Hagglund H et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood 1998; 92: 3599–3604.

    CAS  PubMed  Google Scholar 

  6. McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255–267.

    Article  CAS  PubMed  Google Scholar 

  7. Hagglund H, Remberger M, Klaesson S, Lonnqvist B, Ljungman P, Ringden O . Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood 1998; 92: 4568–4572.

    CAS  PubMed  Google Scholar 

  8. Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010; 16: 157–168.

    Article  PubMed  Google Scholar 

  9. Atkinson K, Biggs J, Dodds A, Concannon A . Cyclosporine-associated hepatotoxicity after allogeneic marrow transplantation in man: differentiation from other causes of posttransplant liver disease. Transplant Proc 1983; 15: 2761–2767.

    Google Scholar 

  10. Ogawa N, Kanda Y, Matsubara M, Asano Y, Nakagawa M, Sakata-Yanagimoto M et al. Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion. Bone Marrow Transplant 2004; 33: 549–552.

    Article  CAS  PubMed  Google Scholar 

  11. Oshima K, Sato M, Terasako K, Kimura S, Okuda S, Kako S et al. Target blood concentrations of CYA and tacrolimus in randomized controlled trials for the prevention of acute GVHD after hematopoietic SCT. Bone Marrow Transplant 2010; 45: 781–782.

    Article  CAS  PubMed  Google Scholar 

  12. Gray RJ . A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  13. Kanda Y Free statistical software: EZR (Easy R) on R commander. (Accessed 1 March 2012, at http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html.)

  14. Lassau N, Auperin A, Leclere J, Bennaceur A, Valteau-Couanet D, Hartmann O . Prognostic value of Doppler-ultrasonography in hepatic veno-occlusive disease. Transplantation 2002; 74: 60–66.

    Article  PubMed  Google Scholar 

  15. van den Bosch MA, van Hoe L . MR imaging findings in two patients with hepatic veno-occlusive disease following bone marrow transplantation. Eur Radiol 2000; 10: 1290–1293.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    M Ashizawa, K Oshima, H Wada, Y Ishihara, K Kawamura, K Sakamoto, M Sato, K Terasako, T Machishima, S Kimura, M Kikuchi, H Nakasone, S Okuda, S Kako, J Kanda, R Yamazaki, A Tanihara, J Nishida & Y Kanda

Authors
  1. M Ashizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Oshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Terasako
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Machishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H Nakasone
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Okuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S Kako
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. J Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. R Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. A Tanihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. J Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Y Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y Kanda.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ashizawa, M., Oshima, K., Wada, H. et al. Hyperbilirubinemia in the early phase after allogeneic HSCT: prognostic significance of the alkaline phosphatase/total bilirubin ratio. Bone Marrow Transplant 48, 94–98 (2013). https://doi.org/10.1038/bmt.2012.130

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.130

Keywords

This article is cited by

Search

Advanced search

Quick links