Azacitidine and gemtuzumab ozogamicin as post-transplant maintenance therapy for high-risk hematologic malignancies

Pavletic SZ, Kumar S, Mohty M, de Lima M, Foran JM, Pasquini M, et al. NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the epidemiology and natural history of relapse following allogeneic cell transplantation. Biol Blood Marrow Transpl. 2010;16:871–90.

Article  Google Scholar 

Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH, et al. NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on treatment of relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2010;16:1467–503.

Article  Google Scholar 

Warlick ED, Cioc A, Defor T, Dolan M, Weisdorf D. Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden. Biol Blood Marrow Transpl. 2009;15:30–8.

Article  Google Scholar 

Armistead PM, de Lima M, Pierce S, Qiao W, Wang X, Thall PF, et al. Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia. Biol Blood Marrow Transpl. 2009;15:1431–8.

Article  Google Scholar 

Kaito S, Wada A, Adachi H, Konuma R, Kishida Y, Nagata A, et al. Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2020;99:1655–65.

Article  CAS  PubMed  Google Scholar 

Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene. 2008;27:5869–85.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116:1908–18.

Article  CAS  PubMed  Google Scholar 

Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood. 2012;119:3361–9.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

Pusic I, Choi J, Fiala MA, Gao F, Holt M, Cashen AF, et al. Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transpl. 2015;21:1761–9.

Article  CAS  Google Scholar 

Craddock C, Jilani N, Siddique S, Yap C, Khan J, Nagra S, et al. Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA Trial. Biol Blood Marrow Transpl. 2016;22:385–90.

Article  CAS  Google Scholar 

El-Cheikh J, Massoud R, Fares E, Kreidieh N, Mahfouz R, Charafeddine M, et al. Low-dose 5-azacytidine as preventive therapy for relapse of AML and MDS following allogeneic HCT. Bone Marrow Transpl. 2017;52:918–21.

Article  CAS  Google Scholar 

de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, et al. CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transpl. 2018;24:2017–24.

Peiper SC, Ashmun RA, Look AT. Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen. Blood. 1988;72:314–21.

Article  CAS  PubMed  Google Scholar 

Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, et al. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013;122:3432–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007;21:66–71.

Article  CAS  PubMed  Google Scholar 

Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005;104:1442–52.

Article  CAS  PubMed  Google Scholar 

Oshikawa G, Kakihana K, Saito M, Aoki J, Najima Y, Kobayashi T, et al. Post-transplant maintenance therapy with azacitidine and gemtuzumab ozogamicin for high-risk acute myeloid leukaemia. Br J Haematol. 2015;169:756–9.

Article  CAS  PubMed  Google Scholar 

de Greef GE, van Putten WL, Boogaerts M, Huijgens PC, Verdonck LF, Vellenga E, et al. Criteria for defining a complete remission in acute myeloid leukaemia revisited. An analysis of patients treated in HOVON-SAKK co-operative group studies. Br J Haematol. 2005;128:184–91.

Article  PubMed  Google Scholar 

Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, et al. Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transpl. 2012;18:280–8.

Article  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the disease risk index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Najima Y, Sadato D, Harada Y, Oboki K, Hirama C, Toya T, et al. Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT. Bone Marrow Transplant. 2021;56:334–46.

Article  CAS  PubMed  Google Scholar 

Ikegame K, Yoshida T, Yoshihara S, Daimon T, Shimizu H, Maeda Y, et al. Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non-complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant. 2015;21:1495–505.

Article  CAS  PubMed  Google Scholar 

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.

CAS  PubMed  Google Scholar 

Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401.e1.

Article  Google Scholar 

Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

Article  CAS  Google Scholar 

de Lima M. New approaches to transplantation in acute myelogenous leukemia. Hematology Am Soc Hematol Educ Program. 2015;2015:596–604.

Article  PubMed  Google Scholar 

Rajvanshi P, Shulman HM, Sievers EL, McDonald GB. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood. 2002;99:2310–4.

Article  CAS  PubMed  Google Scholar 

McKoy JM, Angelotta C, Bennett CL, Tallman MS, Wadleigh M, Evens AM, et al. Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. Leuk Res. 2007;31:599–604.

Article  CAS  PubMed  Google Scholar 

Oran B, de Lima M, Garcia-Manero G, Thall PF, Lin R, Popat U, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020;4:5580–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hassan MA, Moukalled N, El Cheikh J, Bazarbachi A, Abou Dalle I. Azacitidine in combination with venetoclax maintenance post-allogeneic hematopoietic stem cell transplantation in T cell acute lymphoblastic leukemia. Clin Hematol Int. 2023;5:52–5.

Article  PubMed  PubMed Central  Google Scholar 

El-Cheikh J, Bidaoui G, Saleh M, Moukalled N, Abou Dalle I, Bazarbachi A. Venetoclax: a new partner in the novel treatment era for acute myeloid leukemia and myelodysplastic syndrome. Clin Hematol Int. 2023;5:143–54.

Article  PubMed  PubMed Central  Google Scholar 

Levis M, Hamadani M, Logan B, Jones R, Singh A, Litzow M, et al. Gilteritinib as post-transplant maintenance for acute myeloid leukemia with internal tandem duplication mutation of FLT3. J Clin Oncol. 2024:JCO2302474. https://doi.org/10.1200/JCO.23.02474. Online ahead of print.

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.

Article  CAS  PubMed 

Comments (0)

No login
gif