[en] The indication for performing an allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with isolated trisomy 8 AML in first complete remission (CR) is still debated. Here, we compared outcomes of such patients given either allo-HCT or autologous (auto)-HCT. Inclusion criteria consisted of adult patients with de novo AML, isolated trisomy 8, first HCT between 2000 and 2018, CR1 at transplantation, and either auto-HCT or allo-HCT with a HLA-identical sibling donor (MSD) or a 10/10 HLA-matched unrelated donor (UD 10/10). A total of 401 patients met the inclusion criteria. They underwent an auto-HCT (n = 81), allo-HCT with a MSD (n = 186) or allo-HCT with a 10/10 UD (n = 134). At 3 years, relapse incidence, nonrelapse mortality and leukemia-free survival (LFS) were 59%, 5%, and 37%, respectively, in auto-HCT recipients; 31% (P < 0.001), 14% (P = 0.04), and 55% (P = 0.033), respectively, in MSD recipients and 29% (P < 0.001), 13% (P = 0.15), and 59% (P = 0.03), respectively, in UD 10/10 recipients. In multivariate analysis, in comparison to auto-HCT, MSD and UD 10/10 were associated with a lower risk of relapse (HR = 0.47, P < 0.001 and HR = 0.40, P < 0.001, respectively) translating to better LFS (HR = 0.69, P = 0.04 and HR = 0.60, P = 0.03, respectively). There was also a similar trend for overall survival (HR = 0.73, P = 0.12 and HR = 0.65, P = 0.08).
Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison C, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML); analysis of 10 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20. DOI: 10.1182/blood.V98.5.1312
Chevallier P, Labopin M, Nagler A, Ljungman P, Verdonck LF, Volin L, et al. Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality: a survey on behalf of the ALWP of the EBMT. Bone Marrow Transplant. 2009;44:589–94. 10.1038/bmt.2009.68 DOI: 10.1038/bmt.2009.68
Konuma T, Kondo T, Yamashita T, Uchida N, Fukuda T, Ozawa Y, et al. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia harboring trisomy 8. Ann Hematol. 2017;96:469–78. 10.1007/s00277-016-2909-2 DOI: 10.1007/s00277-016-2909-2
Schaich M, Schlenk RF, Al-Ali HK, Dohner H, Ganser A, Heil G, et al. Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. Haematologica. 2007;92:763–70. DOI: 10.3324/haematol.11100
Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED.and the Seattle Marrow Transplant Team Antileukemic effect of chronic graft-versus-host disease. Contribution to improved survival after allogeneic marrow transplantation. N Engl J Med. 1981;304:1529–33. DOI: 10.1056/NEJM198106183042507
Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23:1993–2003. DOI: 10.1200/JCO.2005.08.136
Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C, et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia. 2012;26:2462–8. DOI: 10.1038/leu.2012.135
Sloand EM, Kim S, Fuhrer M, Risitano AM, Nakamura R, Maciejewski JP, et al. Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities. Blood. 2002;100:4427–32. DOI: 10.1182/blood-2002-01-0096
Dickinson AM, Norden J, Li S, Hromadnikova I, Schmid C, Schmetzer H, et al. Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia. Front Immunol. 2017;8:496 10.3389/fimmu.2017.00496 DOI: 10.3389/fimmu.2017.00496
Virtaneva K, Wright FA, Tanner SM, Yuan B, Lemon WJ, Caligiuri MA, et al. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci USA. 2001;98:1124–9. 10.1073/pnas.98.3.1124 DOI: 10.1073/pnas.98.3.1124
Baron F, Ruggeri A, Beohou E, Labopin M, Mohty M, Blaise D, et al. Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT. J Hematol Oncol. 2017;10:128 10.1186/s13045-017-0497-9 DOI: 10.1186/s13045-017-0497-9
Sengsayadeth S, Gatwood KS, Boumendil A, Labopin M, Finke J, Ganser A, et al. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study. Blood Adv. 2018;2:2127–35. 10.1182/bloodadvances.2018019976 DOI: 10.1182/bloodadvances.2018019976
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304. DOI: 10.1097/00007890-197410000-00001
Andersen PK, Klein JP, Zhang MJ. Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–1500. DOI: 10.1002/(SICI)1097-0258(19990630)18:12<1489::AID-SIM140>3.0.CO;2-#
Chang YJ, Zhao XY, Huang XJ. Strategies for enhancing and preserving anti-leukemia effects without aggravating graft-versus-host disease. Front Immunol. 2018;9:3041 10.3389/fimmu.2018.03041 DOI: 10.3389/fimmu.2018.03041
Zittoun R, Suciu S, Watson M, Solbu G, Muus P, Mandelli F, et al. Quality of life in patients with acute myelogenous leukemia in prolonged first complete remission after bone marrow transplantation (allogeneic or autologous) or chemotherapy: a cross-sectional study of the EORTC-GIMEMA AML 8A trial. Bone Marrow Transplant. 1997;20:307–15. DOI: 10.1038/sj.bmt.1700888
Suciu S, Mandelli F, de Witte T, Zittoun R, Gallo E, Labar B, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102:1232–40. DOI: 10.1182/blood-2002-12-3714
Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, 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;109:3658–66. DOI: 10.1182/blood-2006-06-025627
Baron F, Efficace F, Cannella L, Muus P, Trisolini S, Halkes CJM et al. Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: long-term follow up of a phase III study. Am J Hematol. 2020;95:749–58. 10.1002/ajh.25795 DOI: 10.1002/ajh.25795
Baron F, Efficace F, Cannella L, Willemze R, Vignetti M, Muus P, et al. Long-term follow-up of a trial comparing post-remission treatment with autologous or allogeneic bone marrow transplantation or intensive chemotherapy in younger acute myeloid leukemia patients. Haematologica. 2020;105:e13–e16. 10.3324/haematol.2019.221333 DOI: 10.3324/haematol.2019.221333
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;106:2912–9. DOI: 10.1182/blood-2005-05-2004
Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol: Off J Am Soc Clin Oncol. 2017;35:1154–61. 10.1200/JCO.2016.70.7091 DOI: 10.1200/JCO.2016.70.7091
Baron F, Labopin M, Peniket A, Jindra P, Afanasyev B, Sanz MA, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015;121:1048–55. 10.1002/cncr.29163. e-pub ahead of print 2014/11/27 DOI: 10.1002/cncr.29163
Eapen M, Brazauskas R, Hemmer M, Perez WS, Steinert P, Horowitz MM, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018;2:2095–103. 10.1182/bloodadvances.2018021980 DOI: 10.1182/bloodadvances.2018021980