Skip to main content

Advertisement

SpringerLink
Log in

Serum albumin level predicts survival of patients with gastrointestinal acute graft-versus-host disease after allogeneic stem cell transplantation

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

Abstract

In a retrospective single-centre study, we analysed the prognostic impact of factors identifiable at initial diagnosis of acute GVHD (aGVHD). We retrospectively analysed 495 adult patients of whom 308 (62 %) developed acute GVHD (I–IV) and were included in further analysis. Gut aGVHD was diagnosed in 163/308 cases (53 %). Conditioning was myeloablative conditioning (MAC) in 123 (39.9 %) and reduced intensity (RIC) in 185 (60.1 %) patients. Median serum albumin level at diagnosis of aGVHD was 34 g/l, which was used as cut-off for low vs. normal albumin levels. In patients with gut aGVHD, low albumin level at the time of diagnosis of aGVHD was associated with poorer overall survival (OS) which was 52 vs. 67 % at 1 year and 40 vs. 61 % at 3 years, p = 0.015. In patients with only skin aGVHD, 1- and 3-year OS of patients with low vs. normal albumin levels were 72 vs. 72 % and 59 vs. 57 %, respectively, p = 0.69. In multivariate analysis of patients with gut aGVHD, low serum albumin level ≤34 g/l (relative risk (RR) 2.13, p = 0.003), gut aGVHD grades 3–4 (RR 2.70, p = 0.001), RIC (RR 1.84, p = 0.024), matched unrelated donor (RR 1.86, p = 0.18) and mismatched unrelated donor (RR 2.76, p = 0.03) retained negative impact on OS. Subgroup analysis revealed that impact of albumin was restricted to patients with gut aGVHD after RIC. Low serum albumin levels are associated with poorer OS in patients with gut but not skin aGVHD after RIC but not MAC allogeneic stem cell transplantation.

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

Similar content being viewed by others

References

  1. Martin PJ, Schoch G, Fisher L et al (1990) A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 76(8):1464–1472, Oct 15

    PubMed  CAS  Google Scholar 

  2. MacMillan ML, Weisdorf DJ, Wagner JE et al (2002) Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant 8(7):387–394

    Article  PubMed  CAS  Google Scholar 

  3. Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB (2002) Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant 8(3):155–160

    Article  PubMed  Google Scholar 

  4. Xhaard A, Rocha V, Bueno B et al (2012) Steroid-refractory acute GVHD: lack of long-term improved survival using new generation anticytokine treatment. Biol Blood Marrow Transplant 18(3):406–413

    Article  PubMed  CAS  Google Scholar 

  5. Sormani MP, Oneto R, Bruno B et al (2003) A revised day +7 predictive score for transplant-related mortality: serum cholinesterase, total protein, blood urea nitrogen, gamma glutamyl transferase, donor type and cell dose. Bone Marrow Transplant 32(2):205–211

    Article  PubMed  CAS  Google Scholar 

  6. Lunn RA, Sumar N, Bansal AS, Treleaven J (2005) Cytokine profiles in stem cell transplantation: possible use as a predictor of graft-versus-host disease. Hematology 10:107–114

    Article  PubMed  CAS  Google Scholar 

  7. Choi SW, Kitko CL, Braun T et al (2008) Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival. Blood 112:1539–1542

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Fuji S, Kim SW, Fukuda T et al (2008) Preengraftment serum C-reactive protein (CRP) value may predict acute graft-versus host disease and nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 14:510–517

    Article  PubMed  CAS  Google Scholar 

  9. Ferrara JL, Harris AC, Greenson JK et al (2011) Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood 118(25):6702–6708

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Weisdorf SA, Salati M, Longsdorf JA, Ramsay NKC, Sharp HL (1983) Graft-versus-host disease of the intestine: a protein losing enteropathy characterized by fecal α antitrypsin. Gastroenterology 85:1076–1081

    PubMed  CAS  Google Scholar 

  11. Rodriguez-Otero P, Porcher R, Peffault De Latour R et al (2012) Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease. Blood 119(24):5909–5917

    Article  PubMed  CAS  Google Scholar 

  12. Hagen LE, Schechter T, Luk Y, Brodovitch A, Gassas A, Doyle JJ (2011) High alpha-1 antitrypsin clearance predicts severity of gut graft-versus-host disease (GVHD) in childrenPediatr. Transplant 15(6):659–663

    CAS  Google Scholar 

  13. Srinivasan R, Daniels J, Fusaro V et al (2006) Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis. Exp Hematol 34:796–801

    Article  PubMed  CAS  Google Scholar 

  14. Weissinger EM, Schiffer E, Hertenstein B et al (2007) Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 109(12):5511–5519

    Article  PubMed  CAS  Google Scholar 

  15. Paczesny S, Krijanovski OI, Braun TM et al (2009) A biomarker panel for acute graft-versus-host disease. Blood 113:273–278

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Goussetis E, Paisiou A, Kitra V et al (2011) Acute gastrointestinal graft-versus-host disease in pediatric patients: serum albumin on day 5 from initiation of therapy correlates with nonrelapse mortality and overall survival. Biol Blood Marrow Transplant 17(7):1058–1066

    Article  PubMed  CAS  Google Scholar 

  17. Rezvani AR, Storer BE, Storb RF et al (2011) Decreased serum albumin as a biomarker for severe acute graft-versus-host disease after reduced-intensity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 17(11):1594–1601

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Helmberg W, Lanzer G, Zahn R, Weinmayr B, Wagner T, Albert E (1998) Virtual DNA analysis—a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results. Tissue Antigens 51(6):587–592

    Article  PubMed  CAS  Google Scholar 

  19. Marsh SG, Albert ED, Bodmer WF et al (2002) Nomenclature for factors of the HLA system, 2002. Tissue Antigens 60(5):407–464

    Article  PubMed  CAS  Google Scholar 

  20. Robinson J, Walter MJ, Parham P et al (2003) IMGT/HLA and IMGT/MHC: sequence database for the study of the major histocompatibility complex. Nucleic Acids Res 31:311–314

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Schmid C, Schleuning M, Hentrich M et al (2008) High antileukemic efficacy of an intermediate intensity conditioning regimen for allogeneic stem cell transplantation in patients with high-risk acute myeloid leukemia in first complete remission. Bone Marrow Transplant 41(8):721–727

    Article  PubMed  CAS  Google Scholar 

  22. Przepiorka D, Weisdorf D, Martin P et al (1995) 1994 Concensus conference on acute GVHD grading. Bone Marrow Transplant 15:825–828

    PubMed  CAS  Google Scholar 

  23. Harrell F, Lee K (1986) Verifying assumptions of the proportional hazards model. Proc 11th Annual SAS. User’s Group Int 11:823–828

    Google Scholar 

  24. Gooley TA, Chien JW, Pergam SA et al (2010) Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363:2091–2101

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Lee KH, Choi SJ, Lee JH et al (2005) Prognostic factors identifiable at the time of onset of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Haematologica 90(7):939–948

    PubMed  Google Scholar 

  26. Finke J, Bethge WA, Schmoor C et al (2009) Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol 10(9):855–864

    Article  PubMed  CAS  Google Scholar 

  27. Bacigalupo A, Lamparelli T, Milone G et al (2010) Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day + 7 after alternative donor transplants. Bone Marrow Transplant 45(2):385–391

    Article  PubMed  CAS  Google Scholar 

  28. Don BR, Kaysen G (2004) Serum albumin: relationship to inflammation and nutrition. Semin Dial 17:432–437

    Article  PubMed  Google Scholar 

  29. Levine JE, Huber E, Hammer ST et al (2013) Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood 122(8):1505–1509

    Article  PubMed  CAS  Google Scholar 

  30. Harris AC, Ferrara JL, Braun TM et al (2012) Plasma biomarkers of lower gastrointestinal and liver acute GVHD. Blood 119(12):2960–2963

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the nurses of the BMT wards for taking care of our patients, the study nurses for their assistance and the medical technicians and scientists for their work in the BMT laboratories.

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Clinic for stem cell transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20245, Hamburg, Germany

    Francis Ayuk, Lara Bussmann, Tatjana Zabelina, Ronja Veit, Haefaa Alchalby, Christine Wolschke, Heinrich Lellek, Ulrike Bacher, Axel R. Zander & Nicolaus Kröger

Authors
  1. Francis Ayuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lara Bussmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatjana Zabelina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronja Veit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haefaa Alchalby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christine Wolschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Heinrich Lellek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ulrike Bacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Axel R. Zander
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nicolaus Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francis Ayuk.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 37 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ayuk, F., Bussmann, L., Zabelina, T. et al. Serum albumin level predicts survival of patients with gastrointestinal acute graft-versus-host disease after allogeneic stem cell transplantation. Ann Hematol 93, 855–861 (2014). https://doi.org/10.1007/s00277-013-1957-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1957-0

Keywords

Search

Navigation