Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
28
02
2024
accepted:
17
04
2024
revised:
16
04
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
2
5
2024
Statut:
epublish
Résumé
Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000-2004) and last (2015-2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5-35%, LFS: 14.5-24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2.
Identifiants
pubmed: 38697960
doi: 10.1038/s41408-024-01060-4
pii: 10.1038/s41408-024-01060-4
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
76Informations de copyright
© 2024. The Author(s).
Références
Arfons LM, Tomblyn M, Rocha V, Lazarus HM. Second hematopoietic stem cell transplantation in myeloid malignancies. Curr Opin Hematol. 2009;16:112–23.
pubmed: 19468273
pmcid: 2768338
doi: 10.1097/MOH.0b013e3283257a87
de Lima M, Porter DL, Battiwalla M, Bishop MR, Giralt SA, Hardy NM, et al. Proceedings from the National Cancer Institute’s Second international workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: Part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transpl. 2014;20:4–13.
doi: 10.1016/j.bbmt.2013.08.012
Bejanyan N, Weisdorf DJ, Logan BR, Wang H-L, Devine SM, de Lima M, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transpl. 2015;21:454–9.
doi: 10.1016/j.bbmt.2014.11.007
Schmid C, De Wreede LC, Van Biezen A, Finke J, Ehninger G, Ganser A, et al. Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation. Haematologica 2018;103:237–45.
pubmed: 29101205
pmcid: 5792268
doi: 10.3324/haematol.2017.168716
Kharfan-Dabaja MA, Labopin M, Polge E, Nishihori T, Bazarbachi A, Finke J, et al. Association of second allogeneic hematopoietic cell transplant vs donor lymphocyte infusion with overall survival in patients with acute myeloid leukemia relapse. JAMA Oncol. 2018;4:1245.
pubmed: 30003233
doi: 10.1001/jamaoncol.2018.2091
Bazarbachi A, Schmid C, Labopin M, Beelen D, Wolfgang Blau I, Potter V, et al. Evaluation of trends and prognosis over time in patients with AML relapsing after allogeneic hematopoietic cell transplant reveals improved survival for young patients in recent years. Clin Cancer Res. 2020;26:6475–82.
pubmed: 32988970
doi: 10.1158/1078-0432.CCR-20-3134
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140:1345–77.
pubmed: 35797463
doi: 10.1182/blood.2022016867
EBMT. Med-AB Forms Manual. 2019. https://www.ebmt.org/sites/default/files/2019-11/MED-ABFormsManual.pdf . Accessed 28 Feb 2024.
Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission. Bone Marrow Transpl. 2016;51:610–1.
doi: 10.1038/bmt.2015.305
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017. https://doi.org/10.1182/blood-2016-08-733196 .
Bertoli S, Tavitian S, Huynh A, Borel C, Guenounou S, Luquet I, et al. Improved outcome for AML patients over the years 2000–2014. Blood Cancer J. 2017;7:635.
pubmed: 29184070
pmcid: 5802565
doi: 10.1038/s41408-017-0011-1
Spyridonidis A, Labopin M, Savani BN, Niittyvuopio R, Blaise D, Craddock C, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transpl. 2020;55:1114–25.
doi: 10.1038/s41409-020-0803-y
Kassim AA, Savani BN. Hematopoietic stem cell transplantation for acute myeloid leukemia: a review. Hematol Oncol Stem Cell Ther. 2017;10:245–51.
pubmed: 28666104
doi: 10.1016/j.hemonc.2017.05.021
Christopeit M, Kuss O, Finke J, Bacher U, Beelen DW, Bornhäuser M, et al. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol. 2013;31:3259–71.
pubmed: 23918951
doi: 10.1200/JCO.2012.44.7961
Yanada M, Konuma T, Yamasaki S, Kondo T, Fukuda T, Shingai N, et al. Relapse of acute myeloid leukemia after allogeneic hematopoietic cell transplantation: clinical features and outcomes. Bone Marrow Transpl. 2021;56:1126–33.
doi: 10.1038/s41409-020-01163-z
Kharfan-Dabaja MA, Reljic T, Yassine F, Nishihori T, Kumar A, Tawk MM, et al. Efficacy of a second allogeneic hematopoietic cell transplant in relapsed acute myeloid. Leukemia: Results a Syst Rev Meta-Anal Transpl Cell Ther. 2022;28:767.e1–767.e11.
Yerushalmi Y, Shem-Tov N, Danylesko I, Canaani J, Avigdor A, Yerushalmi R, et al. Second hematopoietic stem cell transplantation as salvage therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after a first transplantation. Haematologica 2022;108:1782–92.
pmcid: 10316252
doi: 10.3324/haematol.2022.281877
Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, et al. Outcomes in patients with FLT3-mutated relapsed/ refractory acute myelogenous leukemia who underwent transplantation in the Phase 3 ADMIRAL trial of gilteritinib versus salvage chemotherapy. Transpl Cell Ther. 2023;29:265.e1–265.e10.
doi: 10.1016/j.jtct.2022.12.006
Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3 –internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38:2993–3002.
pubmed: 32673171
doi: 10.1200/JCO.19.03345
Bazarbachi A, Bug G, Baron F, Brissot E, Ciceri F, Dalle IA, et al. Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3 -internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica 2020;105:1507–16.
pubmed: 32241850
pmcid: 7271578
doi: 10.3324/haematol.2019.243410
Bug G, Burchert A, Wagner E-M, Kröger N, Berg T, Güller S, 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;31:2523–5.
pubmed: 28751769
pmcid: 5668491
doi: 10.1038/leu.2017.242
De Lima M, Giralt S, Thall PF, De Padua Silva L, Jones RB, Komanduri K, 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;116:5420–31.
pubmed: 20672358
doi: 10.1002/cncr.25500
Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia 2012;26:381–9.
pubmed: 21886171
doi: 10.1038/leu.2011.234
Bewersdorf JP, Allen C, Mirza A-S, Grimshaw AA, Giri S, Podoltsev NA, et al. Hypomethylating agents and FLT3 inhibitors as maintenance treatment for acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem. Cell Transplant–A Syst Rev Meta-Anal Transpl Cell Ther. 2021;27:997.e1–997.e11.
Schmid C, Labopin M, Schaap N, Veelken H, Schleuning M, Stadler M et al. Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia – a matched pair analysis by the Acute Leukaemia Working Party of EBMT. Br J Haematol. 2019. https://doi.org/10.1111/bjh.15691 .
Schmid C, Labopin M, Schaap N, Veelken H, Brecht A, Stadler M, et al. Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia. Bone Marrow Transpl. 2022;57:215–23.
doi: 10.1038/s41409-021-01515-3
Dholaria B, Savani BN, Labopin M, Luznik L, Ruggeri A, Mielke S, et al. Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT. Haematologica 2020;105:47–58.
pubmed: 31537691
pmcid: 6939532
doi: 10.3324/haematol.2019.219790
Nagler A, Peczynski C, Dholaria B, Labopin M, Valerius T, Dreger P, et al. Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia. Bone Marrow Transpl. 2022;57:1116–23.
doi: 10.1038/s41409-022-01693-8
Rautenberg C, Bergmann A, Germing U, Fischermanns C, Pechtel S, Kaivers J, et al. Prediction of response and survival following treatment with azacitidine for relapse of acute myeloid leukemia and myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation. Cancers 2020;12:2255.
pubmed: 32806572
pmcid: 7464210
doi: 10.3390/cancers12082255
DiNardo CD, Rausch CR, Benton C, Kadia T, Jain N, Pemmaraju N, et al. Clinical experience with the BCL 2‐inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018;93:401–7.
pubmed: 29218851
doi: 10.1002/ajh.25000
Schuler E, Wagner-Drouet E-M, Ajib S, Bug G, Crysandt M, Dressler S, et al. Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group. Ann Hematol. 2021;100:959–68.
pubmed: 33191481
doi: 10.1007/s00277-020-04321-x
Metzelder SK, Schroeder T, Finck A, Scholl S, Fey M, Götze K, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia 2012;26:2353–9.
pubmed: 22504140
doi: 10.1038/leu.2012.105
Rautenberg C, Nachtkamp K, Dienst A, Schmidt PV, Heyn C, Kondakci M, et al. Sorafenib and azacitidine as salvage therapy for relapse of FLT 3‐ ITD mutated AML after allo‐ SCT. Eur J Haematol. 2017;98:348–54.
pubmed: 27893163
doi: 10.1111/ejh.12832
Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N. Engl J Med. 2016;375:143–53.
pubmed: 27410923
pmcid: 5149459
doi: 10.1056/NEJMoa1601202
Stein EM, DiNardo CD, Fathi AT, Pollyea DA, Stone RM, Altman JK, et al. Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood 2019;133:676–87.
pubmed: 30510081
pmcid: 6384189
doi: 10.1182/blood-2018-08-869008
DiNardo CD, Stein EM, De Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable Remissions with Ivosidenib in IDH1 -Mutated Relapsed or Refractory AML. N. Engl J Med. 2018;378:2386–98.
pubmed: 29860938
doi: 10.1056/NEJMoa1716984
Daver NG, Dail M, Garcia JS, Jonas BA, Yee KWL, Kelly KR, et al. Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial. Blood 2023;141:1265–76.
pubmed: 36265087
doi: 10.1182/blood.2022016362
Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MTL, et al. Loss of Mismatched HLA in Leukemia after Stem-Cell Transplantation. N. Engl J Med. 2009;361:478–88.
pubmed: 19641204
doi: 10.1056/NEJMoa0811036
Crucitti L, Crocchiolo R, Toffalori C, Mazzi B, Greco R, Signori A, et al. Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation. Leukemia 2015;29:1143–52.
pubmed: 25371177
doi: 10.1038/leu.2014.314
Tischer J, Engel N, Fritsch S, Prevalsek D, Hubmann M, Schulz C, et al. Second haematopoietic SCT using HLA-haploidentical donors in patients with relapse of acute leukaemia after a first allogeneic transplantation. Bone Marrow Transpl. 2014;49:895–901.
doi: 10.1038/bmt.2014.83
Filippini Velázquez G, Labopin M, Tischer J, Raiola AM, Angelucci E, Kulagin AD, et al. Second haploidentical stem cell transplantation (HAPLO-SCT2) after relapse from a first HAPLO-SCT in acute leukaemia—a study on behalf of the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transpl. 2023;58:907–15.
doi: 10.1038/s41409-023-01985-7
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. https://doi.org/10.1182/bloodadvances.2018019976 .
doi: 10.1182/bloodadvances.2018019976
pubmed: 30143527
pmcid: 6113606
Finke J, Schmoor C, Stelljes M, Burchert A, Dreger P, Hegenbart U, et al. Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial. Bone Marrow Transpl. 2022;57:1664–70.
doi: 10.1038/s41409-022-01777-5
Beelen DW, Stelljes M, Reményi P, Wagner‐Drouet E, Dreger P, Bethge W, et al. Treosulfan compared with REDUCED‐INTENSITY busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: final analysis of a prospective randomized trial. Am J Hematol. 2022;97:1023–34.
pubmed: 35617104
doi: 10.1002/ajh.26620
Freeman SD, Hills RK, Virgo P, Khan N, Couzens S, Dillon R, 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;36:1486–97.
pubmed: 29601212
pmcid: 5959196
doi: 10.1200/JCO.2017.76.3425
Thol F, Gabdoulline R, Liebich A, Klement P, Schiller J, Kandziora C, et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood 2018;132:1703–13.
pubmed: 30190321
doi: 10.1182/blood-2018-02-829911
Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378:1189–99.
pubmed: 29601269
doi: 10.1056/NEJMoa1716863
Zeiser R, Vago L. Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood 2019;133:1290–7.
pubmed: 30578254
doi: 10.1182/blood-2018-10-846824
Sauerer T, Velázquez GF, Schmid C. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: immune escape mechanisms and current implications for therapy. Mol Cancer. 2023;22:180.
pubmed: 37951964
pmcid: 10640763
doi: 10.1186/s12943-023-01889-6