Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
11
06
2021
accepted:
25
10
2021
revised:
06
10
2021
pubmed:
15
11
2021
medline:
20
4
2022
entrez:
14
11
2021
Statut:
ppublish
Résumé
Autologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT.
Identifiants
pubmed: 34775480
doi: 10.1038/s41409-021-01521-5
pii: 10.1038/s41409-021-01521-5
pmc: PMC8821015
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
224-231Informations de copyright
© 2021. The Author(s).
Références
Garcia-Manero G, Othus M, Pagel JM, Radich JP, Fang M, Rizzieri DA, et al. SWOG S1203: a randomized phase III study of standard cytarabine plus daunorubicin (7+3) therapy versus idarubicin with high dose cytarabine (IA) with or without vorinostat (IA+V) in younger patients with previously untreated acute myeloid leukemia (AML). Blood. 2016;128:901.
doi: 10.1182/blood.V128.22.901.901
Walter RB, Othus M, Burnett AK, Löwenberg B, Kantarjian HM, Ossenkoppele GJ, et al. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia. 2015;29:312–20.
doi: 10.1038/leu.2014.242
pubmed: 25113226
Poiré X, Labopin M, Polge E, Blaise D, Chevallier P, Maertens J, et al. Hematopoietic stem cell transplantation for adult patients with isolated NPM1 mutated acute myeloid leukemia in first remission. Am J Hematol. 2019;94:231–9.
pubmed: 30456896
Beyar-Katz O, Lavi N, Ringelstein-Harlev S, Henig I, Yehudai-Ofir D, Haddad N, et al. Superior outcome of patients with favorable-risk acute myeloid leukemia using consolidation with autologous stem cell transplantation. Leuk Lymphoma. 2019;60:2449–56.
doi: 10.1080/10428194.2019.1594214
pubmed: 30943060
Limvorapitak W, Barnett MJ, Hogge DE, Forrest DL, Nevill TJ, Narayanan S, et al. Outcomes of intermediate risk karyotype acute myeloid leukemia in first remission undergoing autologous stem cell transplantation compared with allogeneic stem cell transplantation and chemotherapy consolidation: a retrospective, propensity-score adjusted analysis. Clin Lymphoma Myeloma Leuk. 2018;18:e481–e491. https://doi.org/10.1016/j.clml.2018.07.290 .
doi: 10.1016/j.clml.2018.07.290
pubmed: 30100330
Zhao Y, Chen X, Feng S. Autologous hematopoietic stem cell transplantation in acute myelogenous leukemia. Biol Blood Marrow Transplant. 2019;25:e285–e292. https://doi.org/10.1016/j.bbmt.2019.04.027
doi: 10.1016/j.bbmt.2019.04.027
pubmed: 31054985
Gorin NC, Labopin M, Pabst T, Remenyi P, Wu D, Huynh A, et al. Unrelated matched versus autologous transplantation in adult patients with good and intermediate risk acute myelogenous leukemia in first molecular remission. Am J Hematol. 2017;92:1318–23. https://doi.org/10.1002/ajh.24904 .
doi: 10.1002/ajh.24904
pubmed: 28960419
de Benito AS, Jeker B, Gfeller E, Porret N, Banz Y, Novak U, et al. Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia. Haematologica. 2020;105:e9–e12. https://doi.org/10.3324/haematol.2019.216457 .
doi: 10.3324/haematol.2019.216457
pubmed: 31123030
pmcid: 6939523
Sula M, Bacher U, Oppliger Leibundgut E, Mansouri Taleghani B, Novak U, Pabst T. Excellent outcome after consolidation with autologous transplantation in patients with core binding factor acute myeloid leukemia. Bone Marrow Transplant. 2020;55:1690–3. https://doi.org/10.1038/s41409-019-0762-3 .
doi: 10.1038/s41409-019-0762-3
pubmed: 31796871
Versluis J, Kalin B, Zeijlemaker W, Passweg J, Graux C, Manz MG, et al. Graft-versus-leukemia effect of allogeneic stem-cell transplantation and minimal residual disease in patients with acute myeloid leukemia in first complete remission. JCO Precision Oncology. 2017;1:1–13. https://doi.org/10.1200/PO.17.00078 .
Vyas P, Appelbaum FR, Craddock C. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Biol Blood Marrow Transplant. 2015;21:8–15. https://doi.org/10.1016/j.bbmt.2014.10.026 .
doi: 10.1016/j.bbmt.2014.10.026
pubmed: 25452033
Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118:6037–42. https://doi.org/10.1182/blood-2011-07-370247 .
doi: 10.1182/blood-2011-07-370247
pubmed: 21951683
Mulé MP, Mannis GN, Wood BL, Radich JP, Hwang J, Ramos NR, et al. Multigene measurable residual disease assessment improves acute myeloid leukemia relapse risk stratification in autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:1974–82. https://doi.org/10.1016/j.bbmt.2016.08.014
doi: 10.1016/j.bbmt.2016.08.014
pubmed: 27544285
pmcid: 5072749
Venditti A, Piciocchi A, Candoni A, Melillo L, Calafiore V, Cairoli R, et al. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood. 2019;134:935–45. https://doi.org/10.1182/blood.2018886960
doi: 10.1182/blood.2018886960
pubmed: 31395600
Burchert A, Bug G, Finke J, Stelljes M, Röllig C, Wäsch R, et al. Sorafenib as maintenance therapy post allogeneic stem cell transplantation for FLT3-ITD positive AML: results from the randomized, double-blind, placebo-controlled multicentre SORMAIN trial. Blood. 2018;132:661.
doi: 10.1182/blood-2018-99-112614
Jabbour E, Giralt S, Kantarjian H, Garcia-Manero G, Jagasia M, Kebriaei P, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009;115:1899–905. https://doi.org/10.1002/cncr.24198 .
doi: 10.1002/cncr.24198
pubmed: 19235255
Maples KT, Sabo RT, McCarty JM, Toor AA, Hawks KG. Maintenance azacitidine after myeloablative allogeneic hematopoietic cell transplantation for myeloid malignancies. Leuk Lymphoma. 2018;59:2836–41. https://doi.org/10.1080/10428194.2018.1443334 .
doi: 10.1080/10428194.2018.1443334
pubmed: 29616863
Sandmaier BM, Khaled S, Oran B, Gammon G, Trone D, Frankfurt O. Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant. Am J Hematol. 2018;93:222–31. https://doi.org/10.1002/ajh.24959 .
doi: 10.1002/ajh.24959
pubmed: 29090473
Christopeit M, Labopin M, Gorin N-C, Saraceni F, Passweg J, Forcade E, et al. Allogeneic stem cell transplantation following relapse post autologous stem cell transplantation in adult patients with acute myeloid leukemia: a retrospective analysis of 537 patients from the Acute Leukemia Working Party of the EBMT. Am J Hematol. 2018;93:1532–42. https://doi.org/10.1002/ajh.25285
doi: 10.1002/ajh.25285
pubmed: 30218444
Passweg JR, Labopin M, Christopeit M, Cornelissen J, Pabst T, Socié G, et al. Postremission consolidation by autologous hematopoietic cell transplantation (HCT) for acute myeloid leukemia in first complete remission (CR) and negative implications for subsequent allogeneic HCT in second CR: a study by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Biol Blood Marrow Transplant. 2020;26:659–64. https://doi.org/10.1016/j.bbmt.2019.11.021 .
doi: 10.1016/j.bbmt.2019.11.021
pubmed: 31759159
Foran JM, Pavletic SZ, Logan BR, Agovi-Johnson MA, Pérez WS, Bolwell BJ, et al. Unrelated donor allogeneic transplantation after failure of autologous transplantation for acute myelogenous leukemia: a study from the center for international blood and marrow transplantation research. Biol Blood Marrow Transplant. 2013;19:1102–8. https://doi.org/10.1016/j.bbmt.2013.04.022 .
doi: 10.1016/j.bbmt.2013.04.022
pubmed: 23632091
pmcid: 3691352
Wetzel D, Mueller B, Mansouri B, Seipel K, Leibundgut K, Pabst T. Delayed haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia. Br J Haematol. 2014;168:268–73. https://doi.org/10.1111/bjh.13118
Grünigen I, Raschle J, Rüsges-Wolter I, Mansouri B, Mueller B, Pabst T. The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential. Leuk Res. 2012;36:1325–9. https://doi.org/10.1016/j.leukres.2012.05.027
doi: 10.1016/j.leukres.2012.05.027
Heini AD, Berger MD, Seipel K, Taleghani BM, Baerlocher GM, Leibundgut K, et al. Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years. Leuk Res. 2017;53:28–34. https://doi.org/10.1016/j.leukres.2016.12.001
doi: 10.1016/j.leukres.2016.12.001
pubmed: 27978458
von Grünigen I, Raschle J, Rüsges-Wolter I, Taleghani BM, Mueller BU, Pabst T. The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential. Leuk Res. 2012;36:1325–9. https://doi.org/10.1016/j.leukres.2012.05.027
doi: 10.1016/j.leukres.2012.05.027
Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47. https://doi.org/10.1182/blood-2016-08-733196
doi: 10.1182/blood-2016-08-733196
pubmed: 27895058
pmcid: 5291965
Schuurhuis GJ, Heuser M, Freeman S, Béné MC. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131:1275–91. https://doi.org/10.1182/blood-2017-09-801498
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 Transplant. 2009;15:1628–33. https://doi.org/10.1016/j.bbmt.2009.07.004 .
doi: 10.1016/j.bbmt.2009.07.004
pubmed: 19896087
pmcid: 2861656
Schoemans HM, Lee SJ, Ferrara JL, Wolff D, Levine JE, Schultz KR, et al. EBMT−NIH−CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53:1401–15. https://doi.org/10.1038/s41409-018-0204-7
doi: 10.1038/s41409-018-0204-7
pubmed: 29872128
pmcid: 6786777
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.
pubmed: 7581076
Alvaro de Santiago de B, Barbara J, Eva G, Naomi P, Yara B, Urban N, et al. Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia. Haematologica. 2020;105:e9–e12. https://doi.org/10.3324/haematol.2019.216457
doi: 10.3324/haematol.2019.216457
Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K, et al. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. Bone Marrow Transplant. 2016;51:645–53. https://doi.org/10.1038/bmt.2015.349 .
doi: 10.1038/bmt.2015.349
pubmed: 26808566
Gorin NC, Giebel S, Labopin M, Savani BN, Mohty M, Nagler A. Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects. Bone Marrow Transplant. 2015;50:1495–502. https://doi.org/10.1038/bmt.2015.179 .
doi: 10.1038/bmt.2015.179
pubmed: 26281031
Terwijn M, van Putten WL, Kelder A, van der Velden VH, Brooimans RA, Pabst T, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31:3889–97. https://doi.org/10.1200/jco.2012.45.9628 .
doi: 10.1200/jco.2012.45.9628
pubmed: 24062400
Yoon J-H, Kim H-J, Park S-S, Jeon Y-W, Lee S-E, Cho B-S, et al. Clinical outcome of autologous hematopoietic cell transplantation in adult patients with acute myeloid leukemia: who may benefit from autologous hematopoietic cell transplantation? Biol Blood Marrow Transplant. 2017;23:588–97. https://doi.org/10.1016/j.bbmt.2017.01.070
doi: 10.1016/j.bbmt.2017.01.070
pubmed: 28089879
Oliai C, Schiller G. How to address second and therapy-related acute myelogenous leukaemia. Br J Haematol. 2020;188:116–28. https://doi.org/10.1111/bjh.16354 .
doi: 10.1111/bjh.16354
pubmed: 31863469
Westhus J, Noppeney R, Dührsen U, Hanoun M. FLAG salvage therapy combined with idarubicin in relapsed/refractory acute myeloid leukemia. Leuk Lymphoma. 2019;60:1014–22. https://doi.org/10.1080/10428194.2018.1508670
doi: 10.1080/10428194.2018.1508670
pubmed: 30277107
Fridle C, Medinger M, Wilk MC, Seipel K, Passweg J, Manz MG, et al. Cladribine, cytarabine and idarubicin (CLA-Ida) salvage chemotherapy in relapsed acute myeloid leukemia (AML). Leuk Lymphoma. 2017;58:1068–75. https://doi.org/10.1080/10428194.2016.1235274 .
doi: 10.1080/10428194.2016.1235274
pubmed: 27735213
Delia M, Pastore D, Carluccio P, Pasciolla C, Ricco A, Rossi AR, et al. FLAG-Ida regimen as bridge therapy to allotransplantation in refractory/relapsed acute myeloid leukemia patients. Clin Lymphoma Myeloma Leuk. 2017;17:767–73. https://doi.org/10.1016/j.clml.2017.06.002
doi: 10.1016/j.clml.2017.06.002
pubmed: 28864170
Evers G, Beelen DW, Braess J, Sauerland C, Kolb H-J, Reichle A. et al. Outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) beyond first complete remission (CR1). Blood. 2018;132(Supplement 1):4649. https://doi.org/10.1182/blood-2018-99-116964 .
doi: 10.1182/blood-2018-99-116964
Gilleece MH, Labopin M, Savani BN. Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT. Leukemia. 2020;34:87–99. https://doi.org/10.1038/s41375-019-0527-4
Yanada M, Mori J, Aoki J, Masuko M, Harada K, Uchida N, et al. Allogeneic hematopoietic cell transplantation for patients with a history of multiple relapses of acute myeloid leukemia. Ann Hematol. 2019;98:2179–86. https://doi.org/10.1007/s00277-019-03736-5
doi: 10.1007/s00277-019-03736-5
pubmed: 31203422
Michelis FV, Messner HA, Atenafu EG, McGillis L, Lambie A, Uhm J, et al. Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2. Bone Marrow Transplant. 2015;50:1405–10. https://doi.org/10.1038/bmt.2015.165
doi: 10.1038/bmt.2015.165
pubmed: 26168067
Flach J, Shumilov E, Wiedemann G, Porret N, Shakhanova I, Bürki S, et al. Clinical potential of introducing next-generation sequencing in patients at relapse of acute myeloid leukemia. Hematol Oncol. 2020;38:425–31. https://doi.org/10.1002/hon.2739
Shumilov E, Flach J, Joncourt R, Porret N, Wiedemann G, Angelillo-Scherrer A, et al. Critical evaluation of current molecular MRD strategies including NGS for the management of AML patients with multiple mutations. Hematol Oncol. 2019;37:319–22. https://doi.org/10.1002/hon.2603
Flach J, Shumilov E, Porret N, Shakhanova I, Legros M, Kronig MN, et al. Experiences with next-generation sequencing in relapsed acute myeloid leukemia: a patient case series. Mediterranean J Hematol Infect Dis. 2020;12:e2020068 https://doi.org/10.4084/mjhid.2020.068 .
doi: 10.4084/mjhid.2020.068