Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31

open access

Page views 327
Article views/downloads 455
Get Citation

Connect on Social Media

Connect on Social Media

Optimal timing and conditioning regimen in allogeneic stem cell transplantation for AML

Christoph Schmid1
DOI: 10.5603/AHP.2021.0046
Acta Haematol Pol 2021;52(4):237-241.


In all stages of the disease, allogeneic stem cell transplantation (allo-SCT) plays an important role in the treatment of acute myeloid leukemia. It is an ongoing challenge to find the right balance between the chance of a cure and the risk of dying from side effects of the procedure. With respect to the conditioning, the large number of available protocols, ranging from non-myeloablative to a classical high-dose regimen, offers the opportunity to individualize the treatment, considering both the clinical situation and patient-specific factors such as age and co-morbidities. As a consequence, allo-SCT has become available to a larger percentage of patients, and the question as to whether or not to undergo a transplantation needs to be answered more frequently. The factors to be considered vary widely among patients in remission, those with relapsed disease, and those who never responded to conventional therapy. This review addresses this discussion, focusing on how to define an individualized and weighted treatment concept for each patient.

Article available in PDF format

View PDF Download PDF file


  1. Bornhäuser M, Kienast J, Trenschel R, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012; 13(10): 1035–1044.
  2. Scott BL, Pasquini MC, Logan BR, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017; 35(11): 1154–1161.
  3. Schmid C, Schleuning M, Ledderose G, et al. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005; 23(24): 5675–5687.
  4. Schmid C, Schleuning M, Schwerdtfeger R, et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood. 2006; 108(3): 1092–1099.
  5. Craddock C, Jackson A, Loke J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021; 39(7): 768–778.
  6. Steckel NK, Groth C, Mikesch JH, et al. High-dose melphalan-based sequential conditioning chemotherapy followed by allogeneic haematopoietic stem cell transplantation in adult patients with relapsed or refractory acute myeloid leukaemia. Br J Haematol. 2018; 180(6): 840–853.
  7. Med-AB forms manual. A guide to the completion of the EBMT HSCT Med-AB forms. https://www.ebmt.org/sites/default/files/2019-05/MED-ABFormsManual_0.pdf (April 30, 2021).
  8. Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009; 15(12): 1628–1633.
  9. Spyridonidis A, Labopin M, Savani BN, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transplant. 2020; 55(6): 1114–1125.
  10. 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.
  11. Ferguson P, Hills RK, Grech A, et al. UK NCRI AML Working Group. An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation. Haematologica. 2016; 101(11): 1351–1358.
  12. Versluis J, Cornelissen J, Craddock C, Sanz M. et al.. Acute myeloid leukemia in adults. In: Carreras E, Dufour C, Mohty M, Nagler A. et al.. ed. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies . Springer, Cham 2019: 507–521.
  13. Craddock C, Labopin M, Pillai S, et al. Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukaemia. Leukemia. 2011; 25(5): 808–813.
  14. Zeiser R, Beelen DW, Bethge W, et al. Biology-driven approaches to prevent and treat relapse of myeloid neoplasia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019; 25(4): e128–e140.
  15. Jongen-Lavrencic M, Grob T, Hanekamp D, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018; 378(13): 1189–1199.
  16. Thol F, Gabdoulline R, Liebich A, et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood. 2018; 132(16): 1703–1713.
  17. Freeman SD, Hills RK, Virgo P, et al. Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations. J Clin Oncol. 2018; 36(15): 1486–1497.
  18. Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012; 9(10): 579–590.
  19. Sorror ML, Storb RF, Sandmaier BM, et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol. 2014; 32(29): 3249–3256.
  20. Gratwohl A, Stern M, Brand R, et al. European Group for Blood and Marrow Transplantation and the European Leukemia Net. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009; 115(20): 4715–4726.
  21. Versluis J, Labopin M, Niederwieser D, et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission. Leukemia. 2015; 29(1): 51–57.
  22. Gerstung M, Papaemmanuil E, Martincorena I, et al. Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet. 2017; 49(3): 332–340.
  23. Fenwarth L, Thomas X, de Botton S, et al. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood. 2021; 137(4): 524–532.
  24. Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018; 36(26): 2684–2692.
  25. Tiong IS, Dillon R, Ivey A, et al. Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low-intensity chemotherapy in acute myeloid leukaemia. Br J Haematol. 2021; 192(6): 1026–1030.
  26. Rambaldi A, Grassi A, Masciulli A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015; 16(15): 1525–1536.
  27. Bazarbachi A, Labopin M, Kharfan-Dabaja MA, et al. Allogeneic hematopoietic cell transplantation in acute myeloid leukemia with normal karyotype and isolated Nucleophosmin-1 (NPM1) mutation: outcome strongly correlates with disease status. Haematologica. 2016; 101(1): e34–e37.
  28. Hourigan CS, Dillon LW, Gui G, et al. Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J Clin Oncol. 2020; 38(12): 1273–1283.
  29. Craddock C, Jilani N, Siddique S, et al. Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. Biol Blood Marrow Transplant. 2016; 22(2): 385–390.
  30. Bug G, Burchert A, Wagner EM, et al. Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial). Leukemia. 2017; 31(11): 2523–2525.
  31. Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020; 38(26): 2993–3002.
  32. Mathew NR, Baumgartner F, Braun L, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018; 24(3): 282–291.
  33. Schmid C, Kuball J, Bug G. Defining the role of donor lymphocyte infusion in high-risk hematologic malignancies. J Clin Oncol. 2021; 39(5): 397–418.
  34. Breems DA, Van Putten WLJ, Huijgens PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005; 23(9): 1969–1978.