What the internist should know about stem cell transplant in the elderly patient

  • Michael Medinger
    Division of Hematology, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland

    Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
    Search for articles by this author
  • Jakob Passweg
    Corresponding author: Division of Hematology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
    Division of Hematology, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
    Search for articles by this author


      Most hematological malignancies are increasing in frequency with age. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic option for patients with malignant and non-malignant hematological diseases. The treatment of elderly patients with advanced hematological malignancies has expanded to include reduced intensity conditioning allo-HCT. Physicians increasingly refer older patients for allo-HCT due to more experience and improved supportive care in allo-HCT. This review article discusses the available data regarding the feasibility, tolerability, toxicity, and effectiveness of allo-HCT in different hematological diseases in the elderly. Over the past decade, utilization and survival after allo-HCT have increased in patients ≥70 years. Selected adults ≥70 years with hematological diseases should be evaluated for transplantation.



      BMI (Body mass index), CCI (Charlson Comorbidity Index), CIRS-G (Cumulative Illness Rating Scale–Geriatrics), KF (Kaplan-Feinstein Scale), HCT-CI (Hematopoietic Cell Transplantation Comorbidity Index), PS (Performance Status), ADL (Katz Activities of Daily Living), IADL (Lawton Instrumental Activities of Daily Living), SF-36 PCS (Physical Component Summary of the SF-36), FI (Fried Frailty Index), SF-36 MCS (Mental component summary of the SF-36)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Passweg J.R.
        • Baldomero H.
        • Bader P.
        • Basak G.W.
        • Bonini C.
        • Duarte R.
        • et al.
        European Society for Blood and Marrow Transplantation (EBMT). Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report.
        Bone Marrow Transplant. 2018 Mar 14; ([Epub ahead of print])
        • Lipof J.J.
        • Loh K.P.
        • O'Dwyer K.
        • Liesveld J.L.
        Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia.
        Cancers (Basel). 2018; 4: 10
        • Almeida A.M.
        • Ramos F.
        Acute myeloid leukemia in the older adults.
        Leuk Res Rep. 2016; 6: 1-7
        • Muffly L.
        • Pasquini M.C.
        • 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: 1156-1164
        • Ustun C.
        • Lazarus H.M.
        • Weisdorf D.
        To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century.
        Bone Marrow Transplant. 2013; 48: 1497-1505
        • Aoki J.
        • Kanamori H.
        • Tanaka M.
        • Yamasaki S.
        • Fukuda T.
        • Ogawa H.
        • et al.
        Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia.
        Am. J. Hematol. 2016; 91: 302-307
        • Sorror M.L.
        • Storb R.F.
        • Sandmaier B.M.
        • Maziarz R.T.
        • Pulsipher M.A.
        • Maris M.B.
        • et al.
        Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation.
        J. Clin. Oncol. 2014; 32: 3249-3256
        • Sorror M.L.
        • Estey E.
        Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults Hematol.
        Am. Soc. Hematol. Educ. Program. 2014; : 21-33
        • Gratwohl A.
        • Stern M.
        • Brand R.
        • Apperley J.
        • Baldomero H.
        • de Witte T.
        • et al.
        Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.
        Cancer. 2009; 115: 4715-4726
        • Gökbuget N.
        Treatment of older patients with acute lymphoblastic Leukaemia.
        Drugs Aging. 2018; 35: 11-26
        • Rosko A.
        • Artz A.
        Aging: treating the older patient.
        Biol Blood Marrow Transplant. 2017; 23: 193-200
        • Muffly L.S.
        • Boulukos M.
        • Swanson K.
        • Kocherginsky M.
        • Cerro P.D.
        • 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. 2013; 19: 429-434
        • NCCN, National comprehensive cancer network
        NCCN clinical practice guidelines in oncology, Older adult oncology.
        (Retrieved from)
        • Sorror M.L.
        • Maris M.B.
        • Storb R.
        • Baron F.
        • Sandmaier B.M.
        • Maloney D.G.
        • et al.
        Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.
        Blood. 2005; 106: 2912-2919
        • Armand P.
        • Kim H.T.
        • Logan B.R.
        • Wang Z.
        • Alyea E.P.
        • Kalaycio M.E.
        • et al.
        Validation and refinement of the disease risk index for allogeneic stem cell transplantation.
        Blood. 2014; 123: 3664-3671
        • Muffly L.S.
        • Kocherginsky M.
        • Stock W.
        • Chu Q.
        • Bishop M.R.
        • Godley L.A.
        • et al.
        Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients.
        Haematologica. 2014; 99: 1373-1379
        • Artz A.S.
        Biologic vs. physiologic age in the transplant candidate.
        in: Hematology Am Soc Hematol Educ Program. 2016: 99-105 (ASH:Washington, DC, USA)
        • Carella A.M.
        • Champlin R.
        • Slavin S.
        • Mcsweeney P.
        • Storb R.
        Mini-allografts: ongoing trials in humans.
        Bone Marrow Transplant. 2000; 25: 345-350
        • Bacigalupo A.
        • Ballen K.
        • Rizzo D.
        • Giralt S.
        • Lazarus H.
        • Ho V.
        • et al.
        Defining the intensity of conditioning regimens: working definitions.
        Biol Blood Marrow Transplant. 2009; 15: 1628-1633
        • Bashey Z.A.
        • Zhang X.
        • Brown S.
        • Jackson K.
        • Morris L.E.
        • Holland H.K.
        • et al.
        Comparison of outcomes following transplantation with T-replete HLA-haploidentical donors using post-transplant cyclophosphamide to matched related and unrelated donors for patients with AML and MDS aged 60 years or older.
        Bone Marrow Transplant. 2018 Mar 9; ([Epub ahead of print])
        • Canaani J.
        • Savani B.N.
        • Labopin M.
        • Huang X.J.
        • Ciceri F.
        • Arcese W.
        • et al.
        Donor age determines outcome in acute leukemia patients over 40 undergoing haploidentical hematopoietic cell transplantation.
        Am. J. Hematol. 2018; 93: 246-253
        • Santoro N.
        • Labopin M.
        • Giannotti F.
        • Ehninger G.
        • Niederwieser D.
        • Brecht A.
        • et al.
        Unmanipulated haploidentical in comparison with matched unrelated donor stem cell transplantation in patients 60 years and older with acute myeloid leukemia: a comparative study on behalf of the ALWP of the EBMT.
        J. Hematol. Oncol. 2018; 11: 55
        • Zeiser R.
        • Blazar B.R.
        Acute graft-versus-host disease - biologic process, prevention, and therapy.
        N. Engl. J. Med. 2017; 377: 2167-2179
        • Zeiser R.
        • Blazar B.R.
        Pathophysiology of chronic graft-versus-host disease and therapeutic targets.
        N. Engl. J. Med. 2017; 377: 2565-2579
        • Flowers M.E.
        • Inamoto Y.
        • Carpenter P.A.
        • Lee S.J.
        • Kiem H.P.
        • Petersdorf E.W.
        • et al.
        Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to national institutes of health consensus criteria.
        Blood. 2011; 117: 3214-3219
        • Di Stasi A.
        • Milton D.R.
        • Poon L.M.
        • Hamdi A.
        • Rondon G.
        • Chen J.
        • et al.
        Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors.
        Biol Blood Marrow Transplant. 2014; 20: 1975-1981
        • Anasetti C.
        • Logan B.R.
        • Lee S.J.
        • Waller E.K.
        • Weisdorf D.J.
        • Wingard J.R.
        • et al.
        Blood and Marrow Transplant Clinical Trials Network. Peripheral-blood stem cells versus bone marrow from unrelated donors.
        N. Engl. J. Med. 2012; 367: 1487-1496
        • Medinger M.
        • Passweg J.R.
        Acute myeloid leukaemia genomics.
        Br. J. Haematol. 2017; 179: 530-542
        • Döhner H.
        • Weisdorf D.J.
        • Bloomfield C.D.
        Acute myeloid leukemia.
        N. Engl. J. Med. 2015; 373: 1136-1152
        • Medinger M.
        • Lengerke C.
        • Passweg J.
        Novel therapeutic options in acute myeloid leukemia.
        Leuk. Res. Rep. 2016; 6: 39-49
        • Meyer S.C.
        • Levine R.L.
        Translational implications of somatic genomics in acute myeloid leukaemia.
        Lancet Oncol. 2014; 15: e382-e394
      1. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood;129:424–447.

        • Cornelissen J.J.
        • Versluis J.
        • Passweg J.R.
        • van Putten W.L.
        • Manz M.G.
        • Maertens J.
        • et al.
        HOVON; SAKK Leukemia Groups. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years.
        Leukemia. 2015; 29: 1041-1050
        • Passweg J.R.
        • Baldomero H.
        • Bader P.
        • Bonini C.
        • Cesaro S.
        • Dreger P.
        • et al.
        Hematopoietic stem cell transplantation in Europe 2014: more than 40000 transplants annually.
        Bone Marrow Transplant. 2016; 51: 786-792
        • Cornelissen J.J.
        • van Putten W.L.
        • Verdonck L.F.
        • Theobald M.
        • Jacky E.
        • Daenen S.M.
        • et al.
        Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom?.
        Blood. 2007; 109: 3658-3666
        • Versluis J.
        • Hazenberg C.L.
        • Passweg J.R.
        • van Putten W.L.
        • Maertens J.
        • Biemond B.J.
        • et al.
        Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukemia: a time-dependent analysis.
        Lancet Haematol. 2015; 2: e427-e436
        • Potter V.T.
        • Iacobelli S.
        • van Biezen A.
        • Maertens J.
        • Bourhis J.H.
        • Passweg J.R.
        • et al.
        Comparison of intensive chemotherapy and hypomethylating agents prior to allogeneic stem cell transplantation for advanced MDS. A study of the MDS subcommittee of the Chronic Malignancies Working Party of the EBMT.
        Biol Blood Marrow Transplant. 2016; 22: 1615-1620
        • Kasamon Y.L.
        • Bolaños-Meade J.
        • Prince G.T.
        • Tsai H.L.
        • Mccurdy S.R.
        • Kanakry J.A.
        • et al.
        Outcomes of Nonmyeloablative HLA-Haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults.
        J. Clin. Oncol. 2015; 33: 3152-3161
        • Gokbuget N.
        How I treat older patients with ALL.
        Blood. 2013; 122: 1366-1375
        • Martino R.
        • Giralt S.
        • Caballero M.D.
        • Mackinnon S.
        • Corradini P.
        • Fernández-Avilés F.
        • et al.
        Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning in acute lymphoblastic leukemia: a feasibility study.
        Haematologica. 2003; 88: 555-560
        • Hamaki T.
        • Kami M.
        • Kanda Y.
        • Yuji K.
        • Inamoto Y.
        • Kishi Y.
        • et al.
        Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.
        Bone Marrow Transplant. 2005; 35: 549-556
        • Fathi A.T.
        • Deangelo D.J.
        • Stevenson K.E.
        • Kolitz J.E.
        • Asch J.D.
        • Amrein P.C.
        • et al.
        Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia.
        Cancer. 2016; 122: 2379-2388
        • Pfeifer H.
        • Wettner C.
        • Wassmann B.
        • AAN Giagounidis
        • Stelljes M.
        • Duehrsen U.
        • et al.
        Long term follow-up of 121 elderly patients with philadelphia-positive acute lymphoblastic leukaemia (Ph+ ALL) treated in prospective GMALL trials supports a greater emphasis on allogeneic SCT as definitive postremission.
        Therapy. Blood. 2012; 120: 2608
        • Kröger N.
        • Iacobelli S.
        • Franke G.N.
        • Platzbecker U.
        • Uddin R.
        • Hübel K.
        • et al.
        Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).
        J. Clin. Oncol. 2017; 35: 2157-2164
        • Festuccia M.
        • Baker K.
        • Gooley T.A.
        • Sandmaier B.M.
        • Deeg H.J.
        • Scott B.L.
        Hematopoietic Cell Transplantation in Myelodysplastic Syndromes after Treatment with Hypomethylating Agents.
        Biol Blood Marrow Transplant. 2017; 23: 1509-1514
        • Tefferi A.
        • Guglielmelli P.
        • Lasho T.L.
        • Gangat N.
        • Ketterling R.P.
        • Pardanani A.
        • et al.
        MIPSS70+ Version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for Primary Myelofibrosis.
        J. Clin. Oncol. 2018; 36: 1769-1770
        • Deeg H.J.
        • Bredeson C.
        • Farnia S.
        • Ballen K.
        • Gupta V.
        • Mesa R.A.
        • et al.
        Hematopoietic Cell Transplantation as Curative Therapy for Patients with Myelofibrosis: Long-Term Success in all Age Groups.
        Biol Blood Marrow Transplant. 2015; 21: 1883-1887
        • Sureda A.
        • Dreger P.
        • Bishop M.R.
        • Kroger N.
        • Porter D.L.
        Prevention and treatment of relapse after stem cell transplantation in lymphoid malignancies.
        Bone Marrow Transplant. 2018 May 24; ([Epub ahead of print])
        • Gerull S.
        • Stern M.
        • Ben Aissa A.
        • Manz M.G.
        • Schanz U.
        • Stussi G.
        • et al.
        Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss blood SCT.
        Bone Marrow Transplant. 2013; 48: 408-413
        • Giammarco S.
        • Peffault De Latour R.
        • Sica S.
        • Dufour C.
        • Socie G.
        • Passweg J.
        • et al.
        Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?.
        Blood. 2018; 131: 1989-1992