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:

Transplant Toxicities

Pre-transplant ferritin, albumin and haemoglobin are predictive of survival outcome independent of disease risk index following allogeneic stem cell transplantation

Bone Marrow Transplantation volume 52, pages 870–877 (2017)Cite this article

Subjects

Abstract

Prognostic biomarkers are useful in allogeneic stem cell transplantation (SCT) to predict survival and relapse outcomes. We sought to derive a prognostic scoring system, which augmented the predictive power of the disease risk index (DRI) by incorporating biomarkers and validating their significance after SCT. The outcomes of overall survival (OS) and relapse were assessed with non-relapse mortality (NRM) treated as a competing risk to relapse. Six hundred and two patients were identified through a retrospective analysis of allogeneic SCT recipients for haematological malignancy between 2000 and 2013 in a single centre. Multivariate analysis confirmed the significant predictors of OS pre-SCT were serum ferritin >1000 μg/L (hazard ratio (HR) 1.94, 95% comorbidity index (CI): 1.44–2.60), Hb <100 g/L (HR 1.71, 95% CI: 1.27–2.30) and albumin <30 g/L (HR 2.65, 95% CI: 1.30–5.40). In combination with DRI, these biomarkers significantly improved the Harrell’s C statistic (excluding biomarkers: C=0.60, 95% CI: 0.57–0.64; with biomarkers: C=0.65, 95% CI: 0.62–0.69, P<0.001). Four prognostic groups were derived at the pre-SCT time point: Group 1 (Scores 0–1, n=180, HR=1 (ref)), Group 2 (Scores 2–5, n=298, HR 2.7, 95% CI: 1.8–3.9), Group 3 (Scores 6–7, n=87, HR 4.5, 95% CI: 3.0–6.9) and Group 4 (scores 8–10, n=9, HR 13.4, 95% CI: 5.9–30.2). These prognostic models were also predictive of relapse and NRM and remained valid at day 100, 12 months and 24 months post SCT.

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

Similar content being viewed by others

References

  1. Armand P, Gibson CJ, Cutler C, Ho VT, Koreth J, Alyea EP et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012; 120: 905–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 2014; 123: 3664–3671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lim AB, Roberts AW, Mason K, Bajel A, Szer J, Ritchie DS . Validating the allogeneic stem cell transplantation disease risk index: sample size, follow-up, and local data are important. Transplantation 2015; 99: 128–132.

    Article  CAS  PubMed  Google Scholar 

  4. Kataoka K, Nannya Y, Hangaishi A, Imai Y, Chiba S, Takahashi T et al. Influence of pretransplantation serum ferritin on nonrelapse mortality after myeloablative and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 195–204.

    Article  PubMed  Google Scholar 

  5. Wermke M, Schmidt A, Middeke JM, Sockel K, von Bonin M, Schonefeldt C et al. MRI-based liver iron content predicts for nonrelapse mortality in MDS and AML patients undergoing allogeneic stem cell transplantation. Clin Cancer Res 2012; 18: 6460–6468.

    Article  CAS  PubMed  Google Scholar 

  6. Bazuaye GN, Buser A, Gerull S, Tichelli A, Stern M . Prognostic impact of iron parameters in patients undergoing allo-SCT. Bone Marrow Transplant 2012; 47: 60–64.

    Article  CAS  PubMed  Google Scholar 

  7. Meyer SC, O'Meara A, Buser AS, Tichelli A, Passweg JR, Stern M . Prognostic impact of posttransplantation iron overload after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 440–444.

    Article  CAS  PubMed  Google Scholar 

  8. Tachibana T, Tanaka M, Numata A, Matsumoto K, Tomita N, Fujimaki K et al. Clinical significance of pre- and 1-year post-transplant serum ferritin among adult transplant recipients. Leuk Lymphoma 2014; 55: 1350–1356.

    Article  CAS  PubMed  Google Scholar 

  9. Tachibana T, Tanaka M, Yamazaki E, Numata A, Takasaki H, Kuwabara H et al. Multicenter validation of scoring system of pre-transplant serum ferritin and disease risk in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplant. Leuk Lymphoma 2013; 54: 1318–1320.

    Article  PubMed  Google Scholar 

  10. Vaughn JE, Storer BE, Armand P, Raimondi R, Gibson C, Rambaldi A et al. Design and validation of an augmented hematopoietic cell transplantation-comorbidity index comprising pretransplant ferritin, albumin, and platelet count for prediction of outcomes after allogeneic transplantation. Biol Blood Marrow Transplant 2015; 21: 1418–1424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Artz AS, Logan BR, Zhu X, Akpek G, Martino R, Gupta V et al. Pre-transplant C-reactive protein (CRP), ferritin and albumin as biomarkers to predict transplant related mortality (TRM) after allogeneic hematopoietic cell transplant (HCT). Blood (ASH Annual Meeting Abstracts) 2014; 124: 422.

    Google Scholar 

  12. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  13. Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA . Evaluating the yield of medical tests. JAMA 1982; 247: 2543–2546.

    Article  PubMed  Google Scholar 

  14. Harrell FE Jr, Lee KL, Mark DB . Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996; 15: 361–387.

    Article  PubMed  Google Scholar 

  15. Armand P, Kim HT, Rhodes J, Sainvil MM, Cutler C, Ho VT et al. Iron overload in patients with acute leukemia or MDS undergoing myeloablative stem cell transplantation. Biol Blood Marrow Transplant 2011; 17: 852–860.

    Article  CAS  PubMed  Google Scholar 

  16. Vag T, Kentouche K, Krumbein I, Reichenbach JR, Lopatta E, Renz DM et al. Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results. Pediatr Radiol 2011; 41: 980–984.

    Article  PubMed  Google Scholar 

  17. Trottier BJ, Burns LJ, DeFor TE, Cooley S, Majhail NS . Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI-measured liver iron content. Blood 2013; 122: 1678–1684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Armand P, Kim HT, Virtanen JM, Parkkola RK, Itala-Remes MA, Majhail NS et al. Iron overload in allogeneic hematopoietic cell transplantation outcome: a meta-analysis. Biol Blood Marrow Transplant 2014; 20: 1248–1251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Grossekatthofer M, Guclu ED, Lawitschka A, Matthes-Martin S, Mann G, Minkov M et al. Ferritin concentrations correlate to outcome of hematopoietic stem cell transplantation but do not serve as biomarker of graft-versus-host disease. Ann Hematol 2013; 92: 1121–1128.

    Article  CAS  PubMed  Google Scholar 

  20. Busca A, Falda M, Manzini P, D'Antico S, Valfre A, Locatelli F et al. Iron overload in patients receiving allogeneic hematopoietic stem cell transplantation: quantification of iron burden by a superconducting quantum interference device (SQUID) and therapeutic effectiveness of phlebotomy. Biol Blood Marrow Transplant 2010; 16: 115–122.

    Article  CAS  PubMed  Google Scholar 

  21. Gupta D, Lis CG . Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 2010; 9: 69.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nazha B, Moussaly E, Zaarour M, Weerasinghe C, Azab B . Hypoalbuminemia in colorectal cancer prognosis: nutritional marker or inflammatory surrogate? World J Gastrointest Surg 2015; 7: 370–377.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Deeg HJ, Seidel K, Bruemmer B, Pepe MS, Appelbaum FR . Impact of patient weight on non-relapse mortality after marrow transplantation. Bone Marrow Transplant 1995; 15: 461–468.

    CAS  PubMed  Google Scholar 

  24. Hoffmeister PA, Storer BE, Macris PC, Carpenter PA, Baker KS . Relationship of body mass index and arm anthropometry to outcomes after pediatric allogeneic hematopoietic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant 2013; 19: 1081–1086.

    Article  PubMed  Google Scholar 

  25. Scott BL, Park JY, Deeg HJ, Marr KA, Boeckh M, Chauncey TR et al. Pretransplant neutropenia is associated with poor-risk cytogenetic features and increased infection-related mortality in patients with myelodysplastic syndromes. Biol Blood Marrow Transplant 2008; 14: 799–806.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Robin M, Tabrizi R, Mohty M, Furst S, Michallet M, Bay JO et al. Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). Br J Haematol 2011; 152: 331–339.

    Article  PubMed  Google Scholar 

  27. Deeg HJ, Scott BL, Fang M, Shulman HM, Gyurkocza B, Myerson D et al. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood 2012; 120: 1398–1408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kew AK, Clarke S, Ridler A, Burrell S, Edwards JA, Doucette S et al. A prospective cohort study of the feasibility and efficacy of iron reduction by phlebotomy in recipients of hematopoietic SCT. Bone Marrow Transplant 2015; 50: 457–458.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Haematology and Bone Marrow Transplant Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia

    L Chee, J Szer & D Ritchie

  2. Australian Cancer Research Foundation (ACRF) Translational Laboratory, Level 10, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia

    L Chee & D Ritchie

  3. Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia

    L Chee, M Tacey, B Lim, J Szer & D Ritchie

  4. Melbourne EpiCentre, The Royal Melbourne Hospital, Parkville, Victoria, Australia

    M Tacey

  5. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

    M Tacey

  6. Department of Clinical Haematology, Austin Hospital, Heidelberg, Victoria, Australia

    A Lim

Authors
  1. L Chee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Tacey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Szer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D Ritchie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Chee.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chee, L., Tacey, M., Lim, B. et al. Pre-transplant ferritin, albumin and haemoglobin are predictive of survival outcome independent of disease risk index following allogeneic stem cell transplantation. Bone Marrow Transplant 52, 870–877 (2017). https://doi.org/10.1038/bmt.2017.51

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2017.51

This article is cited by

Search

Advanced search

Quick links