Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC).
Acute GVHD; Acute myeloblastic leukemia; Adolescent and post-adolescent patients; Allogeneic hematopoietic stem cell transplantation; Children; Chronic GVHD; Outcome; Young adults
Abstract :
[en] BACKGROUND: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. METHODS: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation's time: children (< 15 years, n = 564), adolescent and post-adolescent (APA) patients (15-25 years, n = 647) and young adults (26-40 years; n = 1434). RESULTS: With a median follow-up of 4.37 years (min-max 0.18-14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults (p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults-p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p < 0.0001; respectively). Whilst there was no difference between the three groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in APA patients and young adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) (p < 0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29-2.32] for intermediate risk 1, HR 1.50 [1.13-2.01] for intermediate risk 2, HR 2.22 [1.70-2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09-1.61]), disease status at transplant (HR 1.40 [1.10-1.78] for second Complete Remission (CR), HR 2.26 [1.02-4.98] for third CR and HR 3.07 [2.44-3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05-1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1-1.02] by increase of 1 year). CONCLUSION: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.
Disciplines :
Hematology
Author, co-author :
Pochon, Cécile
Detrait, Marie
Dalle, Jean-Hugues
Michel, Gérard
Dhédin, Nathalie
Chalandon, Yves
Brissot, Eolia
Forcade, Edouard
Sirvent, Anne
Izzadifar-Legrand, Faezeh
Michallet, Mauricette
Renard, Cécile
Yakoub-Agha, Ibrahim
Gonzales, Fanny
Bay, Jacques-Olivier
Kanold, Justyna
Cornillon, Jérome
Bulabois, Claude Eric
Angoso, Marie
Nguyen, Stéphanie
Balza, Marie
Chevallier, Patrice
Rialland, Fanny
Bazarbachi, Ali
Beguin, Yves ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie
Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC).
Alloin A-L, Leverger G, Dalle J-H, Galambrun C, Bertrand Y, Baruchel A et al (2017) Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience. Bone Marrow Transplant 52:516–521 DOI: 10.1038/bmt.2016.293
Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE et al (2006) Age and acute myeloid leukemia. Blood 107:3481–3485 DOI: 10.1182/blood-2005-09-3724
Ayuk F, Beelen DW, Bornhäuser M, Stelljes M, Zabelina T, Finke J et al (2018) Relative impact of HLA matching and non-HLA donor characteristics on outcomes of allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 24:2558–2567 DOI: 10.1016/j.bbmt.2018.06.026
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al (2009) Defining the Intensity of Conditioning Regimens: Working Definitions. Biol Blood Marrow Transplant 15:1628–1633 DOI: 10.1016/j.bbmt.2009.07.004
Bastida JM, Cabrero M, Lopez-Godino O, Lopez-Parra M, Sanchez-Guijo F, Lopez-Corral L et al (2015) Influence of donor age in allogeneic stem cell transplant outcome in acute myeloid leukemia and myelodisplastic syndrome. Leuk Res 39:828–834 DOI: 10.1016/j.leukres.2015.05.003
Bitan M, Ahn KW, Millard HR, Pulsipher MA, Abdel-Azim H, Auletta JJ et al (2017) Personalized prognostic risk score for long-term survival for children with acute leukemia after allogeneic transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 23:1523–1530 DOI: 10.1016/j.bbmt.2017.05.011
Bolouri H, Farrar JE, Triche T Jr, Ries RE, Lim EL, Alonzo TA et al (2018) The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med 24(1):103–112 DOI: 10.1038/nm.4439
Bredeson C, LeRademacher J, Kato K, Dipersio J, Agura E, Devine S et al (2013) Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation. Blood 122(24):3871–3878 DOI: 10.1182/blood-2013-08-519009
Büchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Müller-Tidow C et al (2009) Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol 27(1):61–69 DOI: 10.1200/JCO.2007.15.4245
Burke MJ, Gossai N, Cao Q, Macmillan ML, Warlick E, Verneris MR (2014) Similar outcomes between adolescent/young adults and children with AML following allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 49:174–178 DOI: 10.1038/bmt.2013.171
Candoni A, De Marchi F, Zannier ME, Lazzarotto D, Filì C, Dubbini MV et al (2017) High prognostic value of pre-allogeneic stem cell transplantation minimal residual disease detection by WT1 gene expression in AML transplanted in cytologic complete remission. Leuk Res 63:22–27 DOI: 10.1016/j.leukres.2017.10.010
Canner J, Alonzo TA, Franklin J, Freyer DR, Gamis A, Gerbing RB et al (2013) Differences in outcomes of newly diagnosed acute myeloid leukemia for adolescent/young adult and younger patients: a report from the Children’s Oncology Group. Cancer 119:4162–4169 DOI: 10.1002/cncr.28342
Champlin RE (2013) Busulfan or TBI: answer to an age-old question. Blood 122:3856–3857 DOI: 10.1182/blood-2013-10-530006
Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X et al (2013) Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood 122:3863–3870 DOI: 10.1182/blood-2013-07-514448
de Berranger E, Cousien A, Petit A, de Latour PR, Galambrun C, Bertrand Y et al (2014) Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Bone Marrow Transplant 49:382–388 DOI: 10.1038/bmt.2013.185
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 11:945–956 DOI: 10.1016/j.bbmt.2005.09.004
Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M et al (2004) Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood 104:1923–1930 DOI: 10.1182/blood-2004-03-0803
Gaballa S, Saliba R, Oran B, Brammer JE, Chen J, Rondon G et al (2017) Relapse risk and survival in patients with FLT3 mutated acute myeloid leukemia undergoing stem cell transplantation. Am J Hematol 92:331–337 DOI: 10.1002/ajh.24632
Gilleece MH, Labopin M, Yakoub-Agha I, Volin L, Socié G, Ljungman P et al (2021) Measurable residual disease, conditioning regimen intensity and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: a registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood Cancer J. Am J Hematol 11(5):88
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 18:295–304 DOI: 10.1097/00007890-197410000-00001
Horan JT, Alonzo TA, Lyman GH, Gerbing RB, Lange BJ, Ravindranath Y et al (2008) Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children’s Oncology Group. J Clin Oncol off J Am Soc Clin Oncol 26:5797–5801 DOI: 10.1200/JCO.2007.13.5244
Jaime-Pérez JC, Padilla-Medina JR, Fernández LT, Herrera-Garza JL, Gutiérrez-Aguirre CH, Tarín-Arzaga L et al (2018) Outcomes of adolescents and young adults with acute myeloid leukemia treated in a Single Latin American Center. Clin Lymphoma Myeloma Leuk 18:286–292 DOI: 10.1016/j.clml.2018.02.002
Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH et al (2001) Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 98:2043–2051 DOI: 10.1182/blood.V98.7.2043
Konuma T, Mizuno S, Kondo T, Yamaguchi H, Fukuda T, Uchida N et al (2018) Allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia with 11q23 abnormality: a retrospective study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT). Ann Hematol 97(11):2173–2183 DOI: 10.1007/s00277-018-3419-1
Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M et al (2016) Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med 374(1):43–53 DOI: 10.1056/NEJMoa1506002
Lee S, Kim Y-J, Chung N-G, Lim J, Lee D-G, Kim H-J et al (2009) The extent of minimal residual disease reduction after the first 4-week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer 115:561–570 DOI: 10.1002/cncr.24026
Loren AW, Bunin GR, Boudreau C, Champlin RE, Cnaan A, Horowitz MM et al (2006) Impact of donor and recipient sex and parity on outcomes of HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 12:758–769 DOI: 10.1016/j.bbmt.2006.03.015
Luznik L, O’Donnell PV, Fuchs EJ (2012) Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol 39(6):683–693 DOI: 10.1053/j.seminoncol.2012.09.005
Majhail NS, Brazauskas R, Hassebroek A, Bredeson CN, Hahn T, Hale GA et al (2012) Outcomes of allogeneic hematopoietic cell transplantation for adolescent and young adults compared with children and older adults with acute myeloid leukemia. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 18:861–873 DOI: 10.1016/j.bbmt.2011.10.031
Martinez-Cibrian N, Zeiser R, Perez-Simon JA (2020) Graft-versus-host disease prophylaxis: Pathophysiology-based review on current approaches and future directions. Blood Rev 26:100792
Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF et al (2017) Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation [Internet]. N Engl J Med. 10.1056/NEJMoa1706640 (Massachusetts Medical Society; 2017 [cited 2021 Jan 6]) DOI: 10.1056/NEJMoa1706640
Nagler A, Rocha V, Labopin M, Unal A, Ben Othman T, Campos A et al (2013) Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen–a report from the acute leukemia working party of the European group for blood and marrow transplantation. J Clin Oncol off J Am Soc Clin Oncol 31:3549–3556 DOI: 10.1200/JCO.2013.48.8114
Nasir SS, Giri S, Nunnery S, Martin MG (2017) Outcome of adolescents and young adults compared with pediatric patients with acute myeloid and promyelocytic leukemia. Clin Lymphoma Myeloma Leuk 17:126-132.e1 DOI: 10.1016/j.clml.2016.09.011
Pemmaraju N, Kantarjian H, Ravandi F, Nogueras-Gonzalez GM, Huang X, O’Brien S et al (2016) Patient Characteristics and outcomes in adolescents and young adults (AYA) with acute myeloid leukemia (AML). Clin Lymphoma Myeloma Leuk 16:213-222.e2 DOI: 10.1016/j.clml.2015.12.010
Petersdorf EW, Anasetti C, Martin PJ, Gooley T, Radich J, Malkki M et al (2004) Limits of HLA mismatching in unrelated hematopoietic cell transplantation. Blood 104:2976–2980 DOI: 10.1182/blood-2004-04-1674
Rasche M, Zimmermann M, Borschel L, Bourquin J-P, Dworzak M, Klingebiel T et al (2018) Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia 32(10):2167–2177 DOI: 10.1038/s41375-018-0071-7
Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A et al (2018) Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. Hematol Oncol 15:111–140
Schlenk RF, Benner A, Hartmann F, del Valle F, Weber C, Pralle H et al (2003) Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial. Leukemia 17(8):1521–1528 DOI: 10.1038/sj.leu.2403009
Shaw BE, Logan BR, Spellman SR, Marsh SGE, Robinson J, Pidala J et al (2018) Development of an unrelated donor selection score predictive of survival after HCT: donor age matters most. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 24:1049–1056 DOI: 10.1016/j.bbmt.2018.02.006
Steckel NK, Groth C, Mikesch J-H, Trenschel R, Ottinger H, Kordelas L et al (2018) 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 180:840–853 DOI: 10.1111/bjh.15137
Stölzel F, Mohr B, Kramer M, Oelschlägel U, Bochtler T, Berdel WE et al (2016) Karyotype complexity and prognosis in acute myeloid leukemia. Blood Cancer J 6(1):e386
Tomizawa D, Watanabe T, Hanada R, Horibe K, Horikoshi Y, Iwamoto S et al (2015) Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols. Int J Hematol 102:318–326 DOI: 10.1007/s12185-015-1825-x
Tomizawa D, Tanaka S, Kondo T, Hashii Y, Arai Y, Kudo K et al (2017) Allogeneic Hematopoietic Stem Cell Transplantation for Adolescents and Young Adults with Acute Myeloid Leukemia. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 23:1515–1522 DOI: 10.1016/j.bbmt.2017.05.009
Vignon M, Andreoli A, Dhédin N, Lengliné E, Masson E, Robin M et al (2017) Graft-versus-host disease in adolescents and young adults (15–24 Years Old) after allogeneic hematopoietic stem cell transplantation for acute leukemia in first complete remission. J Adolesc Young Adult Oncol 6(2):299–306 DOI: 10.1089/jayao.2016.0060
Wennström L, Wendtland Edslev P, Abrahamsson J, Maxwell Nørgaard J, Fløisand Y, Forestier E et al (2016) Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries. Pediatr Blood Cancer 63(1):83–92 DOI: 10.1002/pbc.25713
Woods WG, Franklin ARK, Alonzo TA, Gerbing RB, Donohue KA, Othus M et al (2013) Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials. Cancer 119:4170–4179 DOI: 10.1002/cncr.28344
Woolfrey A, Klein JP, Haagenson M, Spellman S, Petersdorf E, Oudshoorn M et al (2011) HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 17:885–892 DOI: 10.1016/j.bbmt.2010.09.012
