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:

Allografting

Influence of comorbidities on transplant outcomes in patients aged 50 years or more after myeloablative conditioning incorporating fludarabine, BU and ATG

Bone Marrow Transplantation volume 46, pages 1077–1083 (2011)Cite this article

Subjects

Abstract

Non-myeloablative (MA) and reduced intensity allo-SCT regimens are offered to older patients and/or those with comorbidities because the morbidity and mortality attributable to fully MA conditioning is thought to be unacceptably high. A total of 207 patients aged 50–66 years were treated between 1999 and 2008 with SCT after MA conditioning with fludarabine 50 mg/m2 daily × 5 and i.v. BU 3.2 mg/kg daily × 4.90 (43%) had additional TBI 200 cGy × 2. GVHD prophylaxis was CsA, MTX and thymoglobulin (4.5 mg/kg total dose). As defined by the hematopoietic cell transplantation co-morbidity index (HCT-CI) scoring system 117 (57%) pts scored 0 and 90 (43%) ⩾1. At 5 years OS was 39 vs 54% (P=0.008), disease-free survival 38 vs 49% (P=0.03), TRM 39 vs 19% (P=0.003) and relapse 36 vs 39% (P=ns) in those with scores of 0 and ⩾1, respectively. Multivariate analysis confirmed the influence of HCT-CI scores on TRM (subhazard ratios=2.29; 95% confidence interval=1.29–4.08; P=0.005). We conclude that comorbidities as assessed by the HCT-CI do influence TRM with this regimen but that age alone should not be an indication to prefer a less intense protocol.

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

Similar content being viewed by others

References

  1. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  Google Scholar 

  2. Sorror ML, Giralt S, Sandmaier BM, Delima M, Shahjahan M, Maloney DG et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 2007; 110: 4606–4613.

    Article  CAS  Google Scholar 

  3. Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004; 104: 961–968.

    Article  CAS  Google Scholar 

  4. Banna GL, Aversa S, Sileni VC, Favaretto A, Ghiotto C, Monfardini S . Nonmyeloablative allogeneic stem cell transplantation (NST) after truly nonmyeloablative and reduced intensity conditioning regimens. Crit Rev Oncol Hematol 2004; 51: 171–189.

    Article  Google Scholar 

  5. Barrett AJ, Savani BN . Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents. Leukemia 2006; 20: 1661–1672.

    Article  CAS  Google Scholar 

  6. Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the acute leukemia working party (ALWP) of the European group for blood and marrow transplantation (EBMT). Leukemia 2005; 19: 2304–2312.

    Article  CAS  Google Scholar 

  7. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, lppoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

    Article  CAS  Google Scholar 

  8. Shimoni A, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Benbassar I et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 2006; 20: 322–328.

    Article  CAS  Google Scholar 

  9. Alyea EP, Kim HT, Ho V, Culter C, DeAngelo DJ, Stone R et al. Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 2006; 12: 1047–1055.

    Article  Google Scholar 

  10. Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 2007; 25: 4246–4254.

    Article  Google Scholar 

  11. Russell JA, Tran HT, Quinlan D, Chaudbry A, Duggan P, Stewart D et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant 2002; 8: 468–476.

    Article  CAS  Google Scholar 

  12. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood 2004; 104: 857–864.

    Article  CAS  Google Scholar 

  13. Russell JA, Savoie ML, Balogh A, Turner AR, Larratt L, Chaudhry MA et al. Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 CGY total-body irradiation, and thymoglobulin. Biol Blood Marrow Transplant 2007; 13: 814–821.

    Article  CAS  Google Scholar 

  14. Russell JA, Chaudhry A, Booth K, Brown C, Woodman RC, Valentine K et al. Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience. Biol Blood Marrow Transplant 2000; 6: 109–114.

    Article  CAS  Google Scholar 

  15. Russell JA, Woodman RC, Poon MC, Jones AR, Ruether BA . Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease. Bone Marrow Transplant 1994; 14: 397–401.

    CAS  Google Scholar 

  16. Barrett J . Graft-versus-host disease. In: Treleaven J BJ (ed). Bone Marrow Transplantation in Practice. Edinburgh: Churchill Livingstone, 1992: 257.

    Google Scholar 

  17. Chapiro E, Russell L, Lainey E, Kaltenbach S, Della-Valle V, Hanssens K et al. Activating mutation in the TSLPR gene in B-cell precursor lymphoblastic leukemia. Leukemia 2010; 24: 642–645.

    Article  CAS  Google Scholar 

  18. Guilfoyle R, Demers A, Bredeson C, Richardson E, Szwajcer D, Sftel MD et al. Performance status, but not the hematopoietic cell transplantation comorbidity index (HCT-CI), predicts mortality at a Canadian transplant center. Bone Marrow Transplant 2009; 43: 133–139.

    Article  CAS  Google Scholar 

  19. Labonte L, Iqbal T, Zaidi MA, McDiarmid SA, Hubscb LB, Tay J et al. Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant 2008; 14: 1039–1044.

    Article  Google Scholar 

  20. Majhail NS, Brunstein CG, McAvoy S, Defor TE, AL-Hazzouri A, Setubal D et al. Does the hematopoietic cell transplantation specific comorbidity index predict transplant outcomes? A validation study in a large cohort of umbilical cord blood and matched related donor transplants. Biol Blood Marrow Transplant 2008; 14: 985–992.

    Article  CAS  Google Scholar 

  21. Pollack SM, Steinberg SM, Odom J, Dean RM, Fowler DH, Bishop MR . Assessment of the hematopoietic cell transplantation comorbidity index in non-Hodgkin lymphoma patients receiving reduced-intensity allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 223–230.

    Article  Google Scholar 

  22. Wildes TM, Augustin KM, Sempek D, Zbang QJ, Viji R, Dipersio JF et al. Comorbidities, not age, impact outcomes in autologous stem cell transplant for relapsed non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 840–846.

    Article  CAS  Google Scholar 

  23. Farina L, Bruno B, Patriarca F, Spina F, Sorasio R, Morelli M et al. The hematopoietic cell transplantation comorbidity index (HCT-CI) predicts clinical outcomes in lymphoma and myeloma patients after reduced-intensity or non-myeloablative allogeneic stem cell transplantation. Leukemia 2009; 23: 1131–1138.

    Article  CAS  Google Scholar 

  24. Sorror ML, Storer B, Storb RF . Validation of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in single and multiple institutions: limitations and inferences. Biol Blood Marrow Transplant 2009; 15: 757–758.

    Article  Google Scholar 

  25. Mielcarek M, Storer BE, Sandmaier BM, Sorror ML, Maloney DG, Petersdorf E et al. Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors. Biol Blood Marrow Transplant 2007; 13: 1499–1507.

    Article  Google Scholar 

  26. Sorror M, Storer B, Sandmaier BM, Maloney DG, Chauncey TR, Langston A et al. Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 2008; 112: 1992–2001.

    Article  Google Scholar 

  27. Sorror ML, Storer BE, Maloney DG, Sandmaier BM, Martin PJ, Storb R . Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 2008; 111: 446–452.

    Article  CAS  Google Scholar 

  28. Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.

    Article  CAS  Google Scholar 

  29. Barba P, Pinana JL, Martino R, Valcarcel D, Amoros A, Sureda A et al. Comparison of two pretransplant predictive models and a flexible HCT-CI using different cut off points to determine low-, intermediate-, and high-risk groups: the flexible HCT-CI Is the best predictor of TRM and OS in a population of patients undergoing allo-RIC. Biol Blood Marrow Transplant 2010; 16: 413–420.

    Article  Google Scholar 

  30. Ringden O, Labopin M, Ehninger G, Neiderwieser D, Olsson R, Basara N et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 2009; 27: 4570–4577.

    Article  Google Scholar 

  31. Russell JA, Irish W, Balogh A, Chaudry MA, Savoie ML, Turner AR et al. The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia. Biol Blood Marrow Transplant 2010; 16: 509–514.

    Article  CAS  Google Scholar 

  32. Kasbia G, Al-Gahtani F, Tay J, Labonate L, Tinmouth A, Gillingham A et al. Reduced hemoglobin on day of peripheral blood progenitor cell collection is associated with low graft content of vascular progenitors and increased toxicity after autologous hematopoietic stem cell transplantation. Transfusion 2008; 48: 2421–2428.

    Article  Google Scholar 

  33. Alatrash G, Andersson B, Pelosini M, Rondon G, Qazilbash S, Giralt S et al. Allogeneic hematopoietic stem cell transplant (HSCT) for patients in the 6th and 7th decades of life with AML or MDS using myeloablative, reduced toxicity IV busulfan/fludarabine (BuFlu) conditioning regimen Abstract, American Society for Blood and Marrow Transplantation 2009 BMT Tandem Meeting, 11–15 February 2009, Tampa, FL.

Download references

Acknowledgements

We thank the nursing staff at foothills hospital, Tom Baker cancer centre, Cross cancer institute for their care of these patients.

Author information

Authors and Affiliations

  1. Departments of Medicine and Oncology Foothills Hospital and Tom Baker Cancer Centre, Calgary, Alberta, Canada

    S El Kourashy, M A Chaudhry, M L Savoie, J Storek, N J Bahlis, C B Brown, M Yang, D Quinlan, M Geddes, N Zacarias, A Daly, P Duggan, D A Stewart & J A Russell

  2. Departments of Community Health Sciences and Family Medicine, University of Calgary, Calgary, Alberta, Canada

    T Williamson

  3. Cross Cancer Institute, Edmonton, Alberta, Canada

    A R Turner & L Larratt

Authors
  1. S El Kourashy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Williamson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M A Chaudhry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M L Savoie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A R Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L Larratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Storek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N J Bahlis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C B Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D Quinlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Geddes
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. N Zacarias
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. P Duggan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D A Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. J A Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S El Kourashy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

El Kourashy, S., Williamson, T., Chaudhry, M. et al. Influence of comorbidities on transplant outcomes in patients aged 50 years or more after myeloablative conditioning incorporating fludarabine, BU and ATG. Bone Marrow Transplant 46, 1077–1083 (2011). https://doi.org/10.1038/bmt.2010.257

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.257

Keywords

This article is cited by

Search

Advanced search

Quick links