Haplo-Cord HSCT for AML/MDS

Summary

This study aims to investigate the clinical efficacy of haploidentical-cord blood hematopoietic stem cell transplantation in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), and to analyze the impact of different engraftment patterns (haploidentical engraftment versus cord blood engraftment) on clinical outcomes. By comparing the efficacy of haploidentical-cord blood transplantation in different subtypes of AML and MDS, this research will explore its unique advantages and comparative effectiveness relative to conventional transplantation strategies, so as to provide new evidence for clinical practice. Specific research objectives I. To evaluate the efficacy of haploidentical-cord blood hematopoietic stem cell transplantation for AML and high-risk MDS, including the speed of hematopoietic recovery, immune tolerance, and long-term survival rates. II. To compare the effects of different engraftment patterns (haploidentical engraftment vs. cord blood engraftment) on quality of life, immune tolerance, early complications, and long-term prognosis. III. To identify the clinical advantages and indications of haploidentical-cord blood transplantation through data analysis, and to provide a theoretical basis for clinical decision-making. Novelty of the Study I. Innovation in Hematopoietic Stem Cell Infusion Schedule The present study employs a sequential infusion strategy: haploidentical stem cells are infused on Day 0, and umbilical cord blood cells are infused on Day +6 after transplantation.In contrast to the conventional approach used at most domestic and international centers (including the uzhou Protocol), in which both stem cell sources are infused simultaneously on Day 0, the current protocol delays cord blood infusion. This design confers potential advantages for immune reconstitution and long-term cord blood engraftment. II. Unique Myeloablative Conditioning Regimen The conditioning regimen used in this study is as follows: Fludarabine 25 mg/m² for 5 days, Cytarabine 2 mg/m² for 5 days, intravenous Busulfan 3.2 mg/kg for 3 days, ATG 5 mg/m² for 2 days, Melphalan 60 mg/m² for 2 days, and CTX 50.0 mg/kg daily for 2 days. (For patients in complete remission (CR) with negative MRD before transplantation, Fludarabine and Cytarabine are administered for 3 days instead of 5 days.) Distinct from regimens at other centers, our team administers cyclophosphamide within the critical window after haploidentical stem cell infusion but before cord blood infusion, establishing a novel sequential conditioning model. This approach balances myeloablative intensity and immunomodulation, creating a favorable environment for subsequent long-term cord blood engraftment. III. Engraftment Outcomes and Clinical Value Preliminary clinical experience demonstrates that haplo-cord sequential transplantation following the FA5Cy2Bu3 conditioning regimen combined with low-dose ATG/PTCY can achieve long-term cord blood engraftment in approximately 50% of patients. By comparison, other domestic protocols (e.g., the Suzhou Protocol) rarely result in sustained cord blood engraftment. Achievement of long-term cord blood engraftment is clinically meaningful for reducing relapse rates, lowering the incidence and severity of graft-versus-host disease (GVHD), and improving patient prognosis. These outcomes represent a key advantage of the present protocol.

Timeline

Start

2025-10-20

Primary completion

2028-10-20

Completion

2029-06-30

Publications

• Results Li H, Li X, Chen Y, Li D, Chen X, Zhu Z, Wang Y, Huang J, Chen P, Chen Y, Li N. Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies. Front Immunol. 2021 Nov 4;12:733326. doi: 10.3389/fimmu.2021.733326. eCollection 2021.
• Results Jabbour E, O'Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015 Aug 1;121(15):2517-28. doi: 10.1002/cncr.29383. Epub 2015 Apr 17.
• Results Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017 Jun 30;7(6):e577. doi: 10.1038/bcj.2017.53.
• Results Chen EL, Liu HL, Geng LQ, Tang BL, Zhu XY, Yao W, Song KD, Wan X, Sun GY, Qiang P, Fan Q, Zhou ZW, Zheng CC, Zhang L, Zhang XH, Tong J, Sun ZM. [Unrelated cord blood stem cell transplantation for high-risk/refractory childhood acute myeloid leukemia: a clinical analysis of 160 cases]. Zhonghua Xue Ye Xue Za Zhi. 2021 Jul 14;42(7):549-554. doi: 10.3760/cma.j.issn.0253-2727.2021.07.004. Chinese.
• Results Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet. 2020 Apr 4;395(10230):1146-1162. doi: 10.1016/S0140-6736(19)33018-1.
• Results Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, Allen C, Alsharif U, Alvis-Guzman N, Amini E, Anderson BO, Aremu O, Artaman A, Asgedom SW, Assadi R, Atey TM, Avila-Burgos L, Awasthi A, Ba Saleem HO, Barac A, Bennett JR, Bensenor IM, Bhakta N, Brenner H, Cahuana-Hurtado L, Castaneda-Orjuela CA, Catala-Lopez F, Choi JJ, Christopher DJ, Chung SC, Curado MP, Dandona L, Dandona R, das Neves J, Dey S, Dharmaratne SD, Doku DT, Driscoll TR, Dubey M, Ebrahimi H, Edessa D, El-Khatib Z, Endries AY, Fischer F, Force LM, Foreman KJ, Gebrehiwot SW, Gopalani SV, Grosso G, Gupta R, Gyawali B, Hamadeh RR, Hamidi S, Harvey J, Hassen HY, Hay RJ, Hay SI, Heibati B, Hiluf MK, Horita N, Hosgood HD, Ilesanmi OS, Innos K, Islami F, Jakovljevic MB, Johnson SC, Jonas JB, Kasaeian A, Kassa TD, Khader YS, Khan EA, Khan G, Khang YH, Khosravi MH, Khubchandani J, Kopec JA, Kumar GA, Kutz M, Lad DP, Lafranconi A, Lan Q, Legesse Y, Leigh J, Linn S, Lunevicius R, Majeed A, Malekzadeh R, Malta DC, Mantovani LG, McMahon BJ, Meier T, Melaku YA, Melku M, Memiah P, Mendoza W, Meretoja TJ, Mezgebe HB, Miller TR, Mohammed S, Mokdad AH, Moosazadeh M, Moraga P, Mousavi SM, Nangia V, Nguyen CT, Nong VM, Ogbo FA, Olagunju AT, Pa M, Park EK, Patel T, Pereira DM, Pishgar F, Postma MJ, Pourmalek F, Qorbani M, Rafay A, Rawaf S, Rawaf DL, Roshandel G, Safiri S, Salimzadeh H, Sanabria JR, Santric Milicevic MM, Sartorius B, Satpathy M, Sepanlou SG, Shackelford KA, Shaikh MA, Sharif-Alhoseini M, She J, Shin MJ, Shiue I, Shrime MG, Sinke AH, Sisay M, Sligar A, Sufiyan MB, Sykes BL, Tabares-Seisdedos R, Tessema GA, Topor-Madry R, Tran TT, Tran BX, Ukwaja KN, Vlassov VV, Vollset SE, Weiderpass E, Williams HC, Yimer NB, Yonemoto N, Younis MZ, Murray CJL, Naghavi M. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018 Nov 1;4(11):1553-1568. doi: 10.1001/jamaoncol.2018.2706.
• Results MacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR, Blazar BR, Wagner JE. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood. 2009 Mar 12;113(11):2410-5. doi: 10.1182/blood-2008-07-163238. Epub 2008 Nov 7.
• Results Gomez-Arteaga A, Orfali N, Guarneri D, Cushing MM, Gergis U, Hsu J, Hsu YS, Mayer SA, Phillips AA, Chase SA, Mokhtar AE, Shore TB, Van Besien K. Cord blood transplants supported by unrelated donor CD34+ progenitor cells. Bone Marrow Transplant. 2020 Dec;55(12):2298-2307. doi: 10.1038/s41409-020-0959-5. Epub 2020 Jun 9.
• Results Yun HD, Varma A, Hussain MJ, Nathan S, Brunstein C. Clinical Relevance of Immunobiology in Umbilical Cord Blood Transplantation. J Clin Med. 2019 Nov 14;8(11):1968. doi: 10.3390/jcm8111968.
• Results Hiwarkar P, Qasim W, Ricciardelli I, Gilmour K, Quezada S, Saudemont A, Amrolia P, Veys P. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells. Blood. 2015 Dec 24;126(26):2882-91. doi: 10.1182/blood-2015-06-654780. Epub 2015 Oct 8.
• Results Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, Witherspoon R, Mielcarek M, Deeg JH, Sorror M, Dahlberg A, Sandmaier BM, Salit R, Petersdorf E, Appelbaum FR, Delaney C. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med. 2016 Sep 8;375(10):944-53. doi: 10.1056/NEJMoa1602074.
• Results Massoud R, Gagelmann N, Fritzsche-Friedland U, Zeck G, Heidenreich S, Wolschke C, Ayuk F, Christopeit M, Kroger N. Comparison of immune reconstitution between anti-T-lymphocyte globulin and posttransplant cyclophosphamide as acute graft-versus-host disease prophylaxis in allogeneic myeloablative peripheral blood stem cell transplantation. Haematologica. 2022 Apr 1;107(4):857-867. doi: 10.3324/haematol.2020.271445.
• Results Battipaglia G, Labopin M, Kroger N, Vitek A, Afanasyev B, Hilgendorf I, Schetelig J, Ganser A, Blaise D, Itala-Remes M, Passweg JR, Bonifazi F, Finke J, Ruggeri A, Nagler A, Mohty M. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood. 2019 Sep 12;134(11):892-899. doi: 10.1182/blood.2019000487. Epub 2019 Jul 3.
• Results Lv M, Chang YJ, Huang XJ. Update of the "Beijing Protocol" haplo-identical hematopoietic stem cell transplantation. Bone Marrow Transplant. 2019 Aug;54(Suppl 2):703-707. doi: 10.1038/s41409-019-0605-2.
• Results Xu LP, Wu DP, Han MZ, Huang H, Liu QF, Liu DH, Sun ZM, Xia LH, Chen J, Wang HX, Wang C, Li CF, Lai YR, Wang JM, Zhou DB, Chen H, Song YP, Liu T, Liu KY, Huang XJ. A review of hematopoietic cell transplantation in China: data and trends during 2008-2016. Bone Marrow Transplant. 2017 Nov;52(11):1512-1518. doi: 10.1038/bmt.2017.59. Epub 2017 Apr 24.
• Results Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, Kodera Y. Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States. Biol Blood Marrow Transplant. 2016 Jan;22(1):23-6. doi: 10.1016/j.bbmt.2015.11.001. Epub 2015 Nov 10.
• Results Shouval R, Fein JA, Labopin M, Kroger N, Duarte RF, Bader P, Chabannon C, Kuball J, Basak GW, Dufour C, Galimard JE, Polge E, Lankester A, Montoto S, Snowden JA, Styczynski J, Yakoub-Agha I, Mohty M, Nagler A. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019 Nov;6(11):e573-e584. doi: 10.1016/S2352-3026(19)30158-9. Epub 2019 Aug 30.
• Results Canaani J, Beohou E, Labopin M, Ghavamzadeh A, Beelen D, Hamladji RM, Niederwieser D, Volin L, Markiewicz M, Arnold R, Mufti G, Ehninger G, Socie G, Kroger N, Mohty M, Nagler A. Trends in patient outcome over the past two decades following allogeneic stem cell transplantation for acute myeloid leukaemia: an ALWP/EBMT analysis. J Intern Med. 2019 Apr;285(4):407-418. doi: 10.1111/joim.12854. Epub 2018 Nov 16.

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