open access

Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31
Submitted: 2021-04-28
Accepted: 2021-05-12
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Allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia

Kazimierz Hałaburda1
DOI: 10.5603/AHP.2021.0048
·
Acta Haematol Pol 2021;52(4):245-252.
Affiliations
  1. Institute of Haematology and Transfusion Medicine, 14 Indira Gandhi str., 02-776 Warsaw, Poland

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Published online: 2021-08-31
Submitted: 2021-04-28
Accepted: 2021-05-12

Abstract

The incidence of acute myeloid leukemia (AML) significantly increases with age. Most AML patients are elderly and rarely receive curative treatment. Even those who eventually achieve complete remission have a grim prognosis due to the high risk of relapse. In elderly patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases the probability of prolonged survival compared to standard treatment. The decision as to whether to refer a patient for transplantation must be preceded by a careful risk assessment based on the patient’s remission status, comorbidities, and type of available donor. Although allo-HSCTs are routinely performed in the seventh decade of life, they are not common in those aged over 70. In recent years, the results of allo-HSCT in the elderly have improved, mainly thanks to refined conditioning regimen techniques and better supportive care. It can be anticipated that with growing data on allogeneic transplants in older AML patients, the proportion of this population among transplant recipients will continue to rise.

Abstract

The incidence of acute myeloid leukemia (AML) significantly increases with age. Most AML patients are elderly and rarely receive curative treatment. Even those who eventually achieve complete remission have a grim prognosis due to the high risk of relapse. In elderly patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases the probability of prolonged survival compared to standard treatment. The decision as to whether to refer a patient for transplantation must be preceded by a careful risk assessment based on the patient’s remission status, comorbidities, and type of available donor. Although allo-HSCTs are routinely performed in the seventh decade of life, they are not common in those aged over 70. In recent years, the results of allo-HSCT in the elderly have improved, mainly thanks to refined conditioning regimen techniques and better supportive care. It can be anticipated that with growing data on allogeneic transplants in older AML patients, the proportion of this population among transplant recipients will continue to rise.

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Keywords

acute myeloid leukemia, elderly patients, allogeneic hematopoietic stem cell transplantation

About this article
Title

Allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

245-252

Published online

2021-08-31

DOI

10.5603/AHP.2021.0048

Bibliographic record

Acta Haematol Pol 2021;52(4):245-252.

Keywords

acute myeloid leukemia
elderly patients
allogeneic hematopoietic stem cell transplantation

Authors

Kazimierz Hałaburda

References (64)
  1. Eurostat. http://ec.europa.eu/eurostat (15 April 2021).
  2. World Health Organization. 10 facts on ageing and the life course. http://www.who.int/features/factfiles/ageing/ageing_facts/en/index.html (15 April 2021).
  3. Rodriguez-Abreu D, Bordoni A, Zucca E. Epidemiology of hematological malignancies. Ann Oncol. 2007; 18(Suppl 1): i3–i8.
  4. Juliusson G, Lazarevic V, Hörstedt AS, et al. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 2012; 119(17): 3890–3899.
  5. Shallis RM, Wang R, Davidoff A, et al. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev. 2019; 36: 70–87.
  6. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129(4): 424–447.
  7. Liersch R, Müller-Tidow C, Berdel WE, et al. Prognostic factors for acute myeloid leukaemia in adults--biological significance and clinical use. Br J Haematol. 2014; 165(1): 17–38.
  8. Alibhai SMH, Leach M, Minden MD, et al. Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer. 2009; 115(13): 2903–2911.
  9. Menzin J, Lang K, Earle CC, et al. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med. 2002; 162(14): 1597–1603.
  10. Boddu PC, Kantarjian HM, Ravandi F, et al. Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer. 2017; 123(16): 3050–3060.
  11. Appelbaum F, Gundacker H, Head D, et al. Age and acute myeloid leukemia. Blood. 2006; 107(9): 3481–3485.
  12. Tsai CH, Hou HA, Tang JL, et al. Genetic alterations and their clinical implications in older patients with acute myeloid leukemia. Leukemia. 2016; 30(7): 1485–1492.
  13. Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012; 97(12): 1916–1924.
  14. Medeiros BC, Satram-Hoang S, Hurst D, et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015; 94(7): 1127–1138.
  15. Dhakal P, Shostrom V, Al-Kadhimi ZS, et al. Usefulness of Charlson comorbidity index to predict early mortality and overall survival in older patients with acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2020; 20(12): 804–812.e8.
  16. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8): 2912–2919.
  17. Giles FJ, Borthakur G, Ravandi F, et al. The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol. 2007; 136(4): 624–627.
  18. Maurillo L, Buccisano F, Spagnoli A, et al. Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia. Ann Hematol. 2018; 97(10): 1767–1774.
  19. Bell JA, Galaznik A, Huelin R, et al. Effectiveness and safety of therapeutic regimens for elderly patients with acute myeloid leukemia: a systematic literature review. Clin Lymphoma Myeloma Leuk. 2018; 18(7): e303–e314.
  20. Löwenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989; 7(9): 1268–1274.
  21. Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990; 8(2): 272–279.
  22. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019; 133(1): 7–17.
  23. Sutra Del Galy A, Marouf A, Raffoux E, et al. Allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia or myelodysplastic syndromes: myth and reality. Leukemia. 2021; 35(1): 225–228.
  24. Ustun C, Lazarus HM, Weisdorf D. To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century. Bone Marrow Transplant. 2013; 48(12): 1497–1505.
  25. Duarte RF, Sánchez-Ortega I. HSCT in elderly patients. In: Carreras E, Dufour C, Mohty M. ed. the EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Springer, Cham 2019.
  26. Armand P, Kim HT, Logan BR, et al. Validation and refinement of the disease risk index for allogeneic stem cell transplantation. Blood. 2014; 123(23): 3664–3671.
  27. Au BKC, Gooley TA, Armand P, et al. Reevaluation of the pretransplant assessment of mortality score after allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2015; 21(5): 848–854.
  28. Bonanad S, De la Rubia J, Gironella M, et al. GAH Group. Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale. J Geriatr Oncol. 2015; 6(5): 353–361.
  29. Artz AS, Pollyea DA, Kocherginsky M, et al. Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006; 12(9): 954–964.
  30. Sorror M, Storer B, Sandmaier BM, 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(9): 1992–2001.
  31. Olin RL, Fretham C, Pasquini MC, et al. Geriatric assessment in older alloHCT recipients: association of functional and cognitive impairment with outcomes. Blood Adv. 2020; 4(12): 2810–2820.
  32. Derman BA, Kordas K, Ridgeway J, et al. Results from a multidisciplinary clinic guided by geriatric assessment before stem cell transplantation in older adults. Blood Adv. 2019; 3(22): 3488–3498.
  33. Buckley SA, Wood BL, Othus M, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. 2017; 102(5): 865–873.
  34. Pohlen M, Groth C, Sauer T, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in elderly patients (⩾60 years). Bone Marrow Transplant. 2016; 51(11): 1441–1448.
  35. Veltri L, Rezvani K, Oran B, et al. Allotransplants for patients 65 years or older with high-risk acute myeloid leukemia. Biol Blood Marrow Transplant. 2019; 25(3): 505–514.
  36. Besse K, Maiers M, Confer D, et al. On modeling human leukocyte antigen-identical sibling match probability for allogeneic hematopoietic cell transplantation: estimating the need for an unrelated donor source. Biol Blood Marrow Transplant. 2016; 22(3): 410–417.
  37. Peffault de Latour R, Labopin M, Cornelissen J, et al. Acute Leukemia Working Party of EBMT. In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available? Bone Marrow Transplant. 2015; 50(11): 1411–1415.
  38. Saraceni F, Labopin M, Gorin NC, et al. Acute Leukemia Working Party (ALWP) of the European society for Blood and Marrow Transplantation (EBMT). Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT. J Hematol Oncol. 2016; 9(1): 79.
  39. Isobe M, Konuma T, Masuko M, et al. Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Single cord blood transplantation for acute myeloid leukemia patients aged 60 years or older: a retrospective study in Japan. Ann Hematol. 2021; 100(7): 1849–1861.
  40. Robinson TM, Fuchs EJ, Zhang MJ, et al. Acute Leukemia Working Party of the European Society for Blood and Marrow Transplant and the Center for International Blood and Marrow Transplant Research. Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? Blood Adv. 2018; 2(11): 1180–1186.
  41. Perales MA, Tomlinson B, Zhang MJ, et al. Alternative donor transplantation for acute myeloid leukemia in patients aged ≥50 years: young HLA-matched unrelated or haploidentical donor? Haematologica. 2020; 105(2): 407–413.
  42. Shimoni A, Labopin M, Savani B, et al. Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning: a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation. J Hematol Oncol. 2016; 9(1): 118.
  43. Abdul Wahid SF, Ismail NA, Mohd-Idris MR, et al. Comparison of reduced-intensity and myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and acute lymphoblastic leukemia: a meta-analysis. Stem Cells Dev. 2014; 23(21): 2535–2552.
  44. Devine SM, Owzar K, Blum W, et al. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Cinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015; 33(35): 4167–4175.
  45. Oran B, Giralt S, Saliba R, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transplant. 2007; 13(4): 454–462.
  46. Popat U, de Lima MJ, Saliba RM, et al. Long-term outcome of reduced-intensity allogeneic hematopoietic SCT in patients with AML in CR. Bone Marrow Transplant. 2012; 47(2): 212–216.
  47. Jain T, Alahdab F, Firwana B, et al. Choosing a reduced-intensity conditioning regimen for allogeneic stem cell transplantation, fludarabine/busulfan versus fludarabine melphalan: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2019; 25(4): 728–733.
  48. Zhu S, Liu G, Liu J, et al. Long-term outcomes of treosulfan- vs. busulfan-based conditioning regimen for patients with myelodysplastic syndrome and acute myeloid leukemia before hematopoietic cell transplantation: a systematic review and meta-analysis. Front Oncol. 2020; 10: 591363.
  49. Heinicke T, Labopin M, Polge E, et al. Fludarabine/busulfan versus fludarabine/total-body-irradiation (2 Gy) as conditioning prior to allogeneic stem cell transplantation in patients (≥60 years) with acute myelogenous leukemia: a study of the acute leukemia working party of the EBMT. Bone Marrow Transplant. 2020; 55(4): 729–739.
  50. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129(4): 424–447.
  51. Farag SS, Maharry K, Zhang MJ, et al. Acute Leukemia Committee of the Center for International Blood and Marrow Transplant Research and Cancer and Leukemia Group B. Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60–70 years with acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 2011; 17(12): 1796–1803.
  52. Kurosawa S, Yamaguchi T, Uchida N, et al. Comparison of allogeneic hematopoietic cell transplantation and chemotherapy in elderly patients with non-M3 acute myelogenous leukemia in first complete remission. Biol Blood Marrow Transplant. 2011; 17(3): 401–411.
  53. Versluis J, Hazenberg CLE, Passweg JR, et al. HOVON and SAKK Leukemia Groups. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis. Lancet Haematol. 2015; 2(10): e427–e436.
  54. Østgård LS, Lund JL, Nørgaard JM, et al. Impact of allogeneic stem cell transplantation in first complete remission in acute myeloid leukemia: a national population-based cohort study. Biol Blood Marrow Transplant. 2018; 24(2): 314–323.
  55. Hilberink J, Hazenberg C, van den Berg E, et al. Not type of induction therapy but consolidation with allogeneic hematopoietic cell transplantation determines outcome in older AML patients: A single center experience of 355 consecutive patients. Leuk Res. 2019; 80: 33–39.
  56. Giebel S, Czyz A, Ottmann O, et al. Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2016; 122(19): 2941–2951.
  57. Bazarbachi A, Bug G, Baron F, et al. Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with -internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2020; 105(6): 1507–1516.
  58. de Lima M, Giralt S, Thall PF, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010; 116(23): 5420–5431.
  59. Oran B, de Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020; 4(21): 5580–5588.
  60. Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018; 19(12): 1668–1679.
  61. de Lima M, Oran B, Champlin RE, et al. CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant. 2018; 24(10): 2017–2024.
  62. Maziarz RT, Levis M, Patnaik MM, et al. Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia. Bone Marrow Transplant. 2021; 56(5): 1180–1189.
  63. Levis MJ, Hamadani M, Logan BR, et al. BMT CTN protocol 1506: a phase 3 trial of gilteritinib as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with FLT3-ITD+ AML. Blood. 2019; 134(Suppl 1): 4602.
  64. Kent A, Pollyea D, Winters A, et al. Venetoclax is safe and tolerable as post-transplant maintenance therapy for AML patients at high risk for relapse. Blood. 2020; 136(Suppl 1): 11–12.

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