Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
29
12
2021
accepted:
21
04
2022
revised:
19
04
2022
pubmed:
3
5
2022
medline:
12
7
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
Limited data is available on factors impacting the outcomes of second hematopoietic cell transplantation (HCT2) in patients with secondary acute myeloid leukemia (sAML). This study aimed to assess HCT2 outcome for sAML comparing reduced-intensity (RIC) to myeloablative (MAC) conditioning. Two hundred and fifteen patients were included: RIC (n = 134), MAC (n = 81). The median follow-up was 41.1 (95% CI: 26.7-69.3) and 28.5 (95% CI: 23.9-75.4) months, respectively. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. MVA showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8, p = 0.006)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98, p = 0.042)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5, p = 0.74)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17, p = 0.18)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36, p = 0.6)]. In conclusion, MAC was associated with a lower RI and superior LFS. These results support the use of MAC for eligible patients with sAML who are being considered for HCT2.
Identifiants
pubmed: 35501565
doi: 10.1038/s41409-022-01693-8
pii: 10.1038/s41409-022-01693-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1116-1123Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Granfeldt Ostgard LS, Medeiros BC, Sengelov H, Norgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a National population-based cohort study. J Clin Oncol. 2015;33:3641–9. https://doi.org/10.1200/jco.2014.60.0890 .
doi: 10.1200/jco.2014.60.0890
pubmed: 26304885
Hulegårdh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf Å, et al. Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol. 2015;90:208–14. https://doi.org/10.1002/ajh.23908 .
doi: 10.1002/ajh.23908
pubmed: 25421221
Della Porta MG. Prognosis of secondary acute myeloid leukemia. Leuk Res. 2013;37:857–8. https://doi.org/10.1016/j.leukres.2013.04.016 .
doi: 10.1016/j.leukres.2013.04.016
pubmed: 23664172
Park SH, Chi H-S, Cho Y-U, Jang S, Park C-J. Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia. Blood Res. 2013;48:185 https://doi.org/10.5045/br.2013.48.3.185 .
doi: 10.5045/br.2013.48.3.185
pubmed: 24086938
pmcid: 3786278
Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol. 2001;19:1405–13. https://doi.org/10.1200/jco.2001.19.5.1405 .
doi: 10.1200/jco.2001.19.5.1405
pubmed: 11230485
Kayser S, Döhner K, Krauter J, Köhne C-H, Horst HA, Held G, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117:2137–45. https://doi.org/10.1182/blood-2010-08-301713 .
doi: 10.1182/blood-2010-08-301713
pubmed: 21127174
Zeichner SB, Arellano ML. Secondary adult acute myeloid leukemia: a review of our evolving understanding of a complex disease process. Curr Treatment Options in Oncol. 2015;16. https://doi.org/10.1007/s11864-015-0355-3 .
Litzow MR, Tarima S, Perez WS, Bolwell BJ, Cairo MS, Camitta BM, et al. Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood. 2010;115:1850–7. https://doi.org/10.1182/blood-2009-10-249128 .
doi: 10.1182/blood-2009-10-249128
pubmed: 20032503
pmcid: 2832815
Sengsayadeth S, Labopin M, Boumendil A, Finke J, Ganser A, Stelljes M, et al. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study. Biol Blood Marrow Transpl. 2018;24:1406–14. https://doi.org/10.1016/j.bbmt.2018.04.008 .
doi: 10.1016/j.bbmt.2018.04.008
Schmaelter A-K, Labopin M, Socié G, Itälä-Remes M, Blaise D, Yakoub-Agha I, et al. Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia. Blood Cancer Journal. 2020;10. https://doi.org/10.1038/s41408-020-0296-3 .
Yoshizato T, Nannya Y, Atsuta Y, Shiozawa Y, Iijima-Yamashita Y, Yoshida K, et al. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood. 2017;129:2347–58. https://doi.org/10.1182/blood-2016-12-754796 .
doi: 10.1182/blood-2016-12-754796
pubmed: 28223278
pmcid: 5409449
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. https://doi.org/10.1158/1078-0432.ccr-20-3134 .
doi: 10.1158/1078-0432.ccr-20-3134
pubmed: 32988970
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;4:1245–53. https://doi.org/10.1001/jamaoncol.2018.2091 .
doi: 10.1001/jamaoncol.2018.2091
pubmed: 30003233
Shimoni A, Labopin M, Finke J, Ciceri F, Deconinck E, Kröger N, et al. Donor selection for a second allogeneic stem cell transplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT. Blood Cancer Journal. 2019;9. https://doi.org/10.1038/s41408-019-0251-3 .
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 B. Haematologica. 2018;103:237–45. https://doi.org/10.3324/haematol.2017.168716 .
doi: 10.3324/haematol.2017.168716
pubmed: 29101205
pmcid: 5792268
Saraceni F, Scortechini I, Fiorentini A, Dubbini MV, Mancini G, Federici I, et al. Conditioning regimens for frail patients with acute leukemia undergoing allogeneic stem cell transplant: how to strike gently. Clin Hematol Int. 2021. https://doi.org/10.2991/chi.k.210731.001 .
Potdar RR, Gupta S, Giebel S, Savani BN, Varadi G, Nagler A, et al. Current status and perspectives of irradiation-based conditioning regimens for patients with acute leukemia undergoing hematopoietic stem cell transplantation. Clin Hematol Int. 2019;1:19–27. https://doi.org/10.2991/chi.d.190218.002 .
doi: 10.2991/chi.d.190218.002
pubmed: 34595407
pmcid: 8432382
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. https://doi.org/10.1182/bloodadvances.2018019976 .
doi: 10.1182/bloodadvances.2018019976
pubmed: 30143527
pmcid: 6113606
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;35:2157–64. https://doi.org/10.1200/jco.2016.70.7349 .
doi: 10.1200/jco.2016.70.7349
pubmed: 28463633
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 Transpl. 2009;15:1628–33. https://doi.org/10.1016/j.bbmt.2009.07.004 .
doi: 10.1016/j.bbmt.2009.07.004
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17. https://doi.org/10.1016/0002-9343(80)90380-0 .
doi: 10.1016/0002-9343(80)90380-0
pubmed: 6996481
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. In: Bone Marrow Transplant, vol. 51: England, 2016, 610-1.
Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:2–4. https://doi.org/10.2991/chi.d.191207.001 .
doi: 10.2991/chi.d.191207.001
pubmed: 34595436
pmcid: 8432337
R: A language and environment for statistical computing. In. https://www.R-project.org/ . R Core Team: R Foundation for Statistical Computing, Vienna, Austria., 2020.
Vrhovac R, Labopin M, Ciceri F, Finke J, Holler E, Tischer J, et al. Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes. Bone Marrow Transpl. 2016;51:186–93. https://doi.org/10.1038/bmt.2015.221 .
doi: 10.1038/bmt.2015.221
Ruggeri A, Battipaglia G, Labopin M, Ehninger G, Beelen D, Tischer J, et al. Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study. J Hematol Oncol. 2016;9:89 https://doi.org/10.1186/s13045-016-0321-y .
doi: 10.1186/s13045-016-0321-y
pubmed: 27639553
pmcid: 5027089
Kharfan‐Dabaja MA, Labopin M, Brissot E, Kroger N, Finke J, Ciceri F, et al. Second allogeneic haematopoietic cell transplantation using HLA‐matched unrelated versus T‐cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia. Br J Haematol. 2021;193:592–601. https://doi.org/10.1111/bjh.17426 .
doi: 10.1111/bjh.17426
pubmed: 33838047
Kantarjian H, Kadia T, Dinardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer Journal. 2021;11. https://doi.org/10.1038/s41408-021-00425-3 .
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. 2018. https://doi.org/10.1111/bjh.15691 .
Nagler A, Labopin M, Dholaria B, Finke J, Brecht A, Schanz U, et al. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2019;186:767–76. https://doi.org/10.1111/bjh.15973 .
doi: 10.1111/bjh.15973
pubmed: 31115916
Andreola G, Labopin M, Beelen D, Chevallier P, Tabrizi R, Bosi A, et al. Long-term outcome and prognostic factors of second allogeneic hematopoietic stem cell transplant for acute leukemia in patients with a median follow-up of 10 years. Bone Marrow Transpl. 2015;50:1508–12. https://doi.org/10.1038/bmt.2015.193 .
doi: 10.1038/bmt.2015.193
Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007;25:4938–45. https://doi.org/10.1200/jco.2007.11.6053 .
doi: 10.1200/jco.2007.11.6053
pubmed: 17909197
Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R, et al. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood. 2012;119:1599–606. https://doi.org/10.1182/blood-2011-08-375840 .
doi: 10.1182/blood-2011-08-375840
pubmed: 22167752
Saraceni F, Labopin M, Forcade E, Kröger N, Socié G, Niittyvuopio R, et al. Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT). Cancer Med. 2021;10:23–33. https://doi.org/10.1002/cam4.3593 .
doi: 10.1002/cam4.3593
pubmed: 33242374
Ringden O, Boumendil A, Labopin M, Canaani J, Beelen D, Ehninger G, et al. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Age >69 Years with Acute Myelogenous Leukemia: On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2019. e-pub ahead of print 2019/06/11; https://doi.org/10.1016/j.bbmt.2019.05.037 .
Nagler A, Dholaria B, Labopin M, Socie G, Huynh A, Itälä-Remes M, et al. The impact of anti-thymocyte globulin on the outcomes of Patients with AML with or without measurable residual disease at the time of allogeneic hematopoietic cell transplantation. Leukemia. 2020;34:1144–53. https://doi.org/10.1038/s41375-019-0631-5 .
doi: 10.1038/s41375-019-0631-5
pubmed: 31728052