Drugs & Aging

, Volume 35, Issue 12, pp 1055–1064 | Cite as

Hematopoietic Cell Transplant (HCT) in the Elderly: Myths, Controversies and Unknowns

  • Zeina Al-MansourEmail author
  • Muthalagu Ramanathan
  • Jan Cerny
Review Article


The incidence of most hematological malignancies increases with age. Despite the higher incidence of hematological malignancies in the elderly, the geriatric population is poorly represented in the early oncology clinical trials that established the current standards of care. Hematopoietic cell transplant (HCT), either upfront or at relapse, provides a potentially life-prolonging, often curative option for many patients with hematological malignancies and is considered the standard of care, at least for younger patients. Historically, the concern that older adults undergoing HCT may experience higher morbidity and transplant-related complications has limited the use of this potentially curative option to younger adults, particularly in allogeneic (allo-) HCT. There is growing evidence to support the feasibility, tolerability, and relatively similar effectiveness of both autologous and allo-HCT in the geriatric population. In the allo-HCT setting, nonmyeloablative/reduced-intensity conditioning (NMA/RIC) has expanded the spectrum of patients that can be considered for this approach. Overall survival is largely affected by disease stage, performance status, and comorbidities rather than by chronological age per se. Comprehensive geriatric assessment (CGA) is a promising tool that can uncover frequently undocumented vulnerabilities in an elderly transplant-eligible patient. Serial study of CGA throughout the peri-HCT period may help predict the short- and long-term impact of HCT on an older adult’s functional status and quality of life. Further research is needed to evaluate whether early intervention to improve such vulnerabilities can improve survival and quality of life of these older patients.


Compliance with Ethical Standards


No external funding was used in the preparation of this manuscript.

Conflict of interest

Zeina Al-Mansour, Muthalagu Ramanathan, and Jan Cerny declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.


  1. 1.
    Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(17):2758–65.CrossRefGoogle Scholar
  2. 2.
    Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107(1):265–76.CrossRefGoogle Scholar
  3. 3.
    Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ. Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades. Cancer. 2004;101(11):2667–74.CrossRefGoogle Scholar
  4. 4.
    Juliusson G, Antunovic P, Derolf A, Lehmann S, Möllgård L, Stockelberg D, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009;113(18):4179–87.CrossRefGoogle Scholar
  5. 5.
    Piccirillo JF, Vlahiotis A, Barrett LB, Flood KL, Spitznagel EL, Steyerberg EW. The changing prevalence of comorbidity across the age spectrum. Crit Rev Oncol Hematol. 2008;67(2):124–32.CrossRefGoogle Scholar
  6. 6.
    McCarthy PL, Hahn T, Hassebroek A, Bredeson C, Gajewski J, Hale G, et al. Trends in use of and survival after autologous hematopoietic cell transplantation in North America, 1995–2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2013;19(7):1116–23.CrossRefGoogle Scholar
  7. 7.
    Hahn T, McCarthy PL, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(19):2437–49.CrossRefGoogle Scholar
  8. 8.
    Waterstrat A, Van Zant G. Effects of aging on hematopoietic stem and progenitor cells. Curr Opin Immunol. 2009;21(4):408–13.CrossRefGoogle Scholar
  9. 9.
    Jantunen E. Autologous stem cell transplantation beyond 60 years of age. Bone Marrow Transplant. 2006;38(11):715–20.CrossRefGoogle Scholar
  10. 10.
    Wildes TM, Stirewalt DL, Medeiros B, Hurria A. Hematopoietic stem cell transplantation for hematologic malignancies in older adults: geriatric principles in the transplant clinic. J Natl Compr Cancer Netw JNCCN. 2014;12(1):128–36.CrossRefGoogle Scholar
  11. 11.
    Magagnoli M, Castagna L, Balzarotti M, Sarina B, Timofeeva I, Bertuzzi A, et al. Feasibility and toxicity of high-dose therapy (HDT) supported by peripheral blood stem cells in elderly patients with multiple myeloma and non-Hodgkin’s lymphoma: survey from a single institution. Am J Hematol. 2003;73(4):267–72.CrossRefGoogle Scholar
  12. 12.
    Tempescul A, Ianotto J-C, Hardy E, Quivoron F, Petrov L, Berthou C. Peripheral blood stem cell collection in elderly patients. Ann Hematol. 2010;89(3):317–21.CrossRefGoogle Scholar
  13. 13.
    Micallef IN, Stiff PJ, Stadtmauer EA, Bolwell BJ, Nademanee AP, Maziarz RT, et al. Safety and efficacy of upfront plerixafor + G-CSF versus placebo + G-CSF for mobilization of CD34(+) hematopoietic progenitor cells in patients ≥ 60 and < 60 years of age with non-Hodgkin’s lymphoma or multiple myeloma. Am J Hematol. 2013;88(12):1017–23.CrossRefGoogle Scholar
  14. 14.
    Mileshkin LR, Seymour JF, Wolf MM, Gates P, Januszewicz EH, Joyce P, et al. Cardiovascular toxicity is increased, but manageable, during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for patients aged 60 years and older. Leuk Lymphoma. 2005;46(11):1575–9.CrossRefGoogle Scholar
  15. 15.
    Jantunen E, Kuittinen T, Penttilä K, Lehtonen P, Mahlamäki E, Nousiainen T. High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (> or = 65 years) myeloma patients: comparison with younger patients treated on the same protocol. Bone Marrow Transplant. 2006;37(10):917–22.CrossRefGoogle Scholar
  16. 16.
    Muta T, Miyamoto T, Fujisaki T, Ohno Y, Kamimura T, Kato K, et al. Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. Intern Med Tokyo Jpn. 2013;52(1):63–70.CrossRefGoogle Scholar
  17. 17.
    Wildes TM, Augustin KM, Sempek D, Zhang QJ, Vij R, Dipersio JF, et al. Comorbidities, not age, impact outcomes in autologous stem cell transplant for relapsed non-Hodgkin lymphoma. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2008;14(7):840–6.CrossRefGoogle Scholar
  18. 18.
    Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.CrossRefGoogle Scholar
  19. 19.
    Monfardini S, Ferrucci L, Fratino L, del Lungo I, Serraino D, Zagonel V. Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer. 1996;77(2):395–401.CrossRefGoogle Scholar
  20. 20.
    Sweetenham JW, Pearce R, Philip T, Proctor SJ, Mandelli F, Colombat P, et al. High-dose therapy and autologous bone marrow transplantation for intermediate and high grade non-Hodgkin’s lymphoma in patients aged 55 years and over: results from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma Working Party. Bone Marrow Transplant. 1994;14(6):981–7.PubMedGoogle Scholar
  21. 21.
    Miller CB, Piantadosi S, Vogelsang GB, Marcellus DC, Grochow L, Kennedy MJ, et al. Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant. J Clin Oncol Off J Am Soc Clin Oncol. 1996;14(4):1327–32.CrossRefGoogle Scholar
  22. 22.
    Kusnierz-Glaz CR, Schlegel PG, Wong RM, Schriber JR, Chao NJ, Amylon MD, et al. Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies. J Clin Oncol Off J Am Soc Clin Oncol. 1997;15(1):18–25.CrossRefGoogle Scholar
  23. 23.
    Buadi FK, Micallef IN, Ansell SM, Porrata LF, Dispenzieri A, Elliot MA, et al. Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2006;37(11):1017–22.CrossRefGoogle Scholar
  24. 24.
    Hosing C, Saliba RM, Okoroji G-J, Popat U, Couriel D, Ali T, et al. High-dose chemotherapy and autologous hematopoietic progenitor cell transplantation for non-Hodgkin’s lymphoma in patients > 65 years of age. Ann Oncol Off J Eur Soc Med Oncol. 2008;19(6):1166–71.CrossRefGoogle Scholar
  25. 25.
    Lazarus HM, Carreras J, Boudreau C, Loberiza FR, Armitage JO, Bolwell BJ, et al. Influence of age and histology on outcome in adult non-Hodgkin lymphoma patients undergoing autologous hematopoietic cell transplantation (HCT): a report from the Center For International Blood & Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2008;14(12):1323–33.CrossRefGoogle Scholar
  26. 26.
    Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol. 2001;114(3):600–7.CrossRefGoogle Scholar
  27. 27.
    Kumar SK, Dingli D, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: results from a matched pair analysis. Am J Hematol. 2008;83(8):614–7.CrossRefGoogle Scholar
  28. 28.
    Bashir Q, Shah N, Parmar S, Wei W, Rondon G, Weber DM, et al. Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥ 70 years with multiple myeloma. Leuk Lymphoma. 2012;53(1):118–22.CrossRefGoogle Scholar
  29. 29.
    Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335(2):91–7.CrossRefGoogle Scholar
  30. 30.
    El Cheikh J, Kfoury E, Calmels B, Lemarie C, Stoppa A-M, Bouabdallah R, et al. Age at transplantation and outcome after autologous stem cell transplantation in elderly patients with multiple myeloma. Hematol Oncol Stem Cell Ther. 2011;4(1):30–6.CrossRefGoogle Scholar
  31. 31.
    Klapper W, Kreuz M, Kohler CW, Burkhardt B, Szczepanowski M, Salaverria I, et al. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood. 2012;119(8):1882–7.CrossRefGoogle Scholar
  32. 32.
    Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRefGoogle Scholar
  33. 33.
    Jantunen E, Canals C, Rambaldi A, Ossenkoppele G, Allione B, Blaise D, et al. Autologous stem cell transplantation in elderly patients (> or = 60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry. Haematologica. 2008;93(12):1837–42.CrossRefGoogle Scholar
  34. 34.
    Sun L, Li S, El-Jawahri A, Armand P, Dey BR, Fisher DC, et al. Autologous stem cell transplantation in elderly lymphoma patients in their 70 s: outcomes and analysis. Oncologist. 2018;23(5):624–30.CrossRefGoogle Scholar
  35. 35.
    Dahi PB, Tamari R, Devlin SM, Maloy M, Bhatt V, Scordo M, et al. Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2014;20(12):2004–9.CrossRefGoogle Scholar
  36. 36.
    Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.CrossRefGoogle Scholar
  37. 37.
    Muffly L, Pasquini MC, Martens M, Brazauskas R, Zhu X, Adekola K, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood. 2017;130(9):1156–64.CrossRefGoogle Scholar
  38. 38.
    Estey E, de Lima M, Tibes R, Pierce S, Kantarjian H, Champlin R, et al. Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007;109(4):1395–400.CrossRefGoogle Scholar
  39. 39.
    Alousi AM, Le-Rademacher J, Saliba RM, Appelbaum FR, Artz A, Benjamin J, et al. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood. 2013;121(13):2567–73.CrossRefGoogle Scholar
  40. 40.
    Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(17):2859–67.CrossRefGoogle Scholar
  41. 41.
    Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, et al. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000;96(13):4096–102.PubMedGoogle Scholar
  42. 42.
    Wallen H, Gooley TA, Deeg HJ, Pagel JM, Press OW, Appelbaum FR, et al. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(15):3439–46.CrossRefGoogle Scholar
  43. 43.
    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(5):1550–8.CrossRefGoogle Scholar
  44. 44.
    Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A, et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(3):405–11.CrossRefGoogle Scholar
  45. 45.
    Sorror ML, Sandmaier BM, Storer BE, Franke GN, Laport GG, Chauncey TR, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA. 2011;306(17):1874–83.CrossRefGoogle Scholar
  46. 46.
    Koreth J, Aldridge J, Kim HT, Alyea EP, Cutler C, Armand P, et al. Reduced-intensity conditioning hematopoietic stem cell transplantation in patients over 60 years: hematologic malignancy outcomes are not impaired in advanced age. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2010;16(6):792–800.CrossRefGoogle Scholar
  47. 47.
    Brunner AM, Kim HT, Coughlin E, Alyea EP, Armand P, Ballen KK, et al. Outcomes in patients age 70 or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2013;19(9):1374–80.CrossRefGoogle Scholar
  48. 48.
    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(8):2912–9.CrossRefGoogle Scholar
  49. 49.
    Kataoka K, Nannya Y, Ueda K, Kumano K, Takahashi T, Kurokawa M. Differential prognostic impact of pretransplant comorbidity on transplant outcomes by disease status and time from transplant: a single Japanese transplant centre study. Bone Marrow Transplant. 2010;45(3):513–20.CrossRefGoogle Scholar
  50. 50.
    Takasaki H, Tanaka M, Tachibana T, Numata A, Fujimaki K, Sakai R, et al. Prognostic factors in patients aged 50 years or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancy. Int J Hematol. 2012;95(3):291–8.CrossRefGoogle Scholar
  51. 51.
    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 J Am Soc Blood Marrow Transplant. 2008;14(9):985–92.CrossRefGoogle Scholar
  52. 52.
    Bayraktar UD, Shpall EJ, Liu P, Ciurea SO, Rondon G, de Lima M, et al. Hematopoietic cell transplantation-specific comorbidity index predicts inpatient mortality and survival in patients who received allogeneic transplantation admitted to the intensive care unit. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(33):4207–14.CrossRefGoogle Scholar
  53. 53.
    McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(11):1878–87.CrossRefGoogle Scholar
  54. 54.
    Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, et al. Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: long-term follow-up of a randomized clinical trial. JAMA Oncol. 2016;2(12):1583–9.CrossRefGoogle Scholar
  55. 55.
    Fraser CJ, Bhatia S, Ness K, Carter A, Francisco L, Arora M, et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. Blood. 2006;108(8):2867–73.CrossRefGoogle Scholar
  56. 56.
    El-Jawahri A, Pidala J, Inamoto Y, Chai X, Khera N, Wood WA, et al. Impact of age on quality of life, functional status, and survival in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2014;20(9):1341–8.CrossRefGoogle Scholar
  57. 57.
    Pidala J, Craig BM, Lee SJ, Majhail N, Quinn G, Anasetti C. Practice variation in physician referral for allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2013;48(1):63–7.CrossRefGoogle Scholar
  58. 58.
    Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(25):3457–65.CrossRefGoogle Scholar
  59. 59.
    Muffly LS, Boulukos M, Swanson K, Kocherginsky M, Cerro PD, Schroeder L, et al. Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2013;19(3):429–34.CrossRefGoogle Scholar
  60. 60.
    Muffly LS, Kocherginsky M, Stock W, Chu Q, Bishop MR, Godley LA, et al. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 2014;99(8):1373–9.CrossRefGoogle Scholar
  61. 61.
    Broder MS, Quock TP, Chang E, Reddy SR, Agarwal-Hashmi R, Arai S, et al. The cost of hematopoietic stem-cell transplantation in the United States. Am Health Drug Benefits. 2017;10(7):366–74.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Khera N, Zeliadt SB, Lee SJ. Economics of hematopoietic cell transplantation. Blood. 2012;120(8):1545–51.CrossRefGoogle Scholar
  63. 63.
    Diep PP, Melberg HO, Brinch L, Buechner J, Fløisand Y, Gedde-Dahl T, et al. Cost-utility of allogeneic hematopoietic stem cell transplantation in Norway. Bone Marrow Transplant. 2018;53(5):657–60.CrossRefGoogle Scholar
  64. 64.
    Matthes-Martin S, Pötschger U, Barr R, Martin M, Boztug H, Klingebiel T, et al. Costs and cost-effectiveness of allogeneic stem cell transplantation in children are predictable. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2012;18(10):1533–9.CrossRefGoogle Scholar
  65. 65.
    Shah GL, Winn A, Lin P-J, Klein A, Sprague KA, Smith HP, et al. Cost implications of comorbidity for autologous stem cell transplantation in elderly patients with multiple myeloma using SEER-medicare. Bone Marrow Res. 2016;2016:3645623.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.University of Massachusetts School of MedicineWorcesterUSA

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