Low dose post-transplant cyclophosphamide and sirolimus induce mixed chimerism with CTLA4-Ig or lymphocyte depletion in an MHC-mismatched murine allotransplantation model – Bone Marrow Transplantation

  • Granot N, Storb R. History of hematopoietic cell transplantation: challenges and progress. Haematologica. 2020;105:2716–29. https://doi.org/10.3324/haematol.2019.245688.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hsieh MM, Fitzhugh CD, Tisdale JF. Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now. Blood. 2011;118:1197–207. https://doi.org/10.1182/blood-2011-01-332510.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • DeFilipp Z, Hefazi M, Chen YB, Blazar BR. Emerging approaches to improve allogeneic hematopoietic cell transplantation outcomes for nonmalignant diseases. Blood. 2022;139:3583–93. https://doi.org/10.1182/blood.2020009014.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fitzhugh CD, Cordes S, Taylor T, Coles W, Roskom K, Link M, et al. At least 20% donor myeloid chimerism is necessary to reverse the sickle phenotype after allogeneic HSCT. Blood. 2017;130:1946–8. https://doi.org/10.1182/blood-2017-03-772392.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saraf SL, Rondelli D. Allogeneic hematopoietic stem cell transplantation for adults with sickle cell disease. J Clin Med. 2019; 8. https://doi.org/10.3390/jcm8101565.

  • Walters MC, Patience M, Leisenring W, Rogers ZR, Aquino VM, Buchanan GR, et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transpl. 2001;7:665–73. https://doi.org/10.1053/bbmt.2001.v7.pm11787529.

    Article 
    CAS 

    Google Scholar
     

  • Pawlowska AB, Sun V, Rosenthal J. Haploidentical stem cell transplantation for patients with sickle cell disease: current status. Transfus Apher Sci. 2022;61:103534 https://doi.org/10.1016/j.transci.2022.103534.

    Article 
    PubMed 

    Google Scholar
     

  • Bejanyan N, Haddad H, Brunstein C. Alternative donor transplantation for acute myeloid leukemia. J Clin Med. 2015;4:1240–68. https://doi.org/10.3390/jcm4061240.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reddy P, Negrin R, Hill GR. Mouse models of bone marrow transplantation. Biol Blood Marrow Transpl. 2008;14:129–35. https://doi.org/10.1016/j.bbmt.2007.10.021.

    Article 

    Google Scholar
     

  • Santos GW, Owens AH. Production of graft-versus-host disease in the rat and its treatment with cytotoxic agents. Nature. 1966;210:139–40. https://doi.org/10.1038/210139a0.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Gress RE, Kanakry CG. Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Invest. 2019;129:2357–73. https://doi.org/10.1172/JCI124218.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, et al. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17:242–9. https://doi.org/10.1111/tid.12365.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lin CJ, Vader JM, Slade M, DiPersio JF, Westervelt P, Romee R. Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation. Cancer. 2017;123:1800–9. https://doi.org/10.1002/cncr.30534.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17:822–30. https://doi.org/10.1111/tid.12455.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ahn JS, Park S, Im SA, Yoon SS, Lee JS, Kim BK, et al. High-dose versus low-dose cyclophosphamide in combination with G-CSF for peripheral blood progenitor cell mobilization. Korean J Intern Med. 2005;20:224–31. https://doi.org/10.3904/kjim.2005.20.3.224.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nishikawa T, Miyahara E, Kurauchi K, Watanabe E, Ikawa K, Asaba K, et al. Mechanisms of fatal cardiotoxicity following high-dose cyclophosphamide therapy and a method for its prevention. PLoS ONE. 2015;10:e0131394 https://doi.org/10.1371/journal.pone.0131394. e-pub ahead of print 20150626

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winkelmann N, Desole M, Hilgendorf I, Ernst T, Sayer HG, Kunert C, et al. Comparison of two dose levels of cyclophosphamide for successful stem cell mobilization in myeloma patients. J Cancer Res Clin Oncol. 2016;142:2603–10. https://doi.org/10.1007/s00432-016-2270-9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fitzhugh CD, Weitzel RP, Hsieh MM, Phang OA, Madison C, Luznik L, et al. Sirolimus and post transplant Cy synergistically maintain mixed chimerism in a mismatched murine model. Bone Marrow Transpl. 2013;48:1335–41. https://doi.org/10.1038/bmt.2013.60.

    Article 
    CAS 

    Google Scholar
     

  • Patel DA, Akinsete AM, de la Fuente J, Kassim AA. Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease: an update. Hematol Oncol Stem Cell Ther. 2020;13:91–97. https://doi.org/10.1016/j.hemonc.2020.01.002.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Kanakry CG. Optimized timing of post-transplantation cyclophosphamide in MHC-haploidentical murine hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2020;26:230–41. https://doi.org/10.1016/j.bbmt.2019.09.030.

    Article 
    CAS 

    Google Scholar
     

  • Wang Y, Wu DP, Liu QF, Xu LP, Liu KY, Zhang XH, et al. Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. J Hematol Oncol. 2019;12:88. https://doi.org/10.1186/s13045-019-0781-y.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hsieh MM, Fitzhugh CD, Weitzel RP, Link ME, Coles WA, Zhao X, et al. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA. 2014;312:48–56. https://doi.org/10.1001/jama.2014.7192.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998;31:335–40. https://doi.org/10.1016/s0009-9120(98)00045-9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ugurlu MM, Griffin MD, Tazelaar HD, McGregor CG. Synergistic effects of CTLA-4Ig and sirolimus on orthotopic lung-allograft survival and histology. Transplantation. 2003;76:489–95. https://doi.org/10.1097/01.TP.0000072374.48680.E0.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fitzhugh CD, Hsieh MM, Taylor T, Coles W, Roskom K, Wilson D, et al. Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT. Blood Adv. 2017;1:652–61. https://doi.org/10.1182/bloodadvances.2016002972.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sobel RA, Hanzakos JL, Blanchette BW, Williams AM, Dellapelle P, Colvin RB. Anti-T cell monoclonal antibodies in vivo. I. Inhibition of delayed hypersensitivity but not cutaneous basophil hypersensitivity reactions. J Immunol. 1987;138:2500–6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aparicio-Vergara M, Shiri-Sverdlov R, de Haan G, Hofker MH. Bone marrow transplantation in mice as a tool for studying the role of hematopoietic cells in metabolic and cardiovascular diseases. Atherosclerosis. 2010;213:335–44. https://doi.org/10.1016/j.atherosclerosis.2010.05.030.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Small TN, Robinson WH, Miklos DB. B cells and transplantation: an educational resource. Biol Blood Marrow Transpl. 2009;15:104–13. https://doi.org/10.1016/j.bbmt.2008.10.016.

    Article 

    Google Scholar
     

  • Alhabbab R, Blair P, Elgueta R, Stolarczyk E, Marks E, Becker PD, et al. Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model. Sci Rep. 2015;5:11554. https://doi.org/10.1038/srep11554.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bhat DK, Olkhanud PB, Gangaplara A, Seifuddin F, Pirooznia M, Biancotto A, et al. Early Myeloid Derived Suppressor Cells (eMDSCs) are associated with high donor myeloid chimerism following haploidentical HSCT for sickle cell disease. Front Immunol. 2021;12:757279. https://doi.org/10.3389/fimmu.2021.757279.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, et al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest. 2011;121:3645–56. https://doi.org/10.1172/JCI46274.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lal G, Nakayama Y, Sethi A, Singh AK, Burrell BE, Kulkarni N, et al. Interleukin-10 from marginal zone precursor b-cell subset is required for costimulatory blockade-induced transplantation tolerance. Transplantation. 2015;99:1817–28. https://doi.org/10.1097/TP.0000000000000718.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bhat P, Leggatt G, Waterhouse N, Frazer IH. Interferon-gamma derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity. Cell Death Dis. 2017;8:e2836 https://doi.org/10.1038/cddis.2017.67.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:362 https://doi.org/10.3389/fimmu.2016.00362.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grenz A, Schenk M, Zipfel A, Viebahn R. TNF-alpha and its receptors mediate graft rejection and loss after liver transplantation. Clin Chem Lab Med. 2000;38:1183–5. https://doi.org/10.1515/CCLM.2000.184.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kroemer A, Edtinger K, Li XC. The innate natural killer cells in transplant rejection and tolerance induction. Curr Opin Organ Transpl. 2008;13:339–43. https://doi.org/10.1097/MOT.0b013e3283061115.

    Article 

    Google Scholar
     

  • Pietra BA, Wiseman A, Bolwerk A, Rizeq M, Gill RG. CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II. J Clin Invest. 2000;106:1003–10. https://doi.org/10.1172/JCI10467.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Powell JD, Fitzhugh C, Kang EM, Hsieh M, Schwartz RH, Tisdale JF. Low-dose radiation plus rapamycin promotes long-term bone marrow chimerism. Transplantation. 2005;80:1541–5. https://doi.org/10.1097/01.tp.0000185299.72295.90.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sawant DV, Hamilton K, Vignali DA. Interleukin-35: expanding its job profile. J Interferon Cytokine Res. 2015;35:499–512. https://doi.org/10.1089/jir.2015.0015.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Colvin MM, Smith CA, Tullius SG, Goldstein DR. Aging and the immune response to organ transplantation. J Clin Invest. 2017;127:2523–9. https://doi.org/10.1172/JCI90601.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heinbokel T, Quante M, Iske J, Nian Y, Maenosono R, Minami K, et al. CTLA4-Ig prolongs graft survival specifically in young but not old mice. Am J Transpl. 2021;21:488–502. https://doi.org/10.1111/ajt.16218.

    Article 
    CAS 

    Google Scholar
     

  • Maenosono R, Nian Y, Iske J, Liu Y, Minami K, Rommel T, et al. Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion. Am J Transpl. 2021;21:3239–55. https://doi.org/10.1111/ajt.16611.

    Article 
    CAS 

    Google Scholar
     

  • Merli P, Caruana I, De Vito R, Strocchio L, Weber G, Bufalo FD, et al. Role of interferon-gamma in immune-mediated graft failure after allogeneic hematopoietic stem cell transplantation. Haematologica. 2019;104:2314–23. https://doi.org/10.3324/haematol.2019.216101.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014;15:23–36. https://doi.org/10.1517/14656566.2014.852537.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Harper SJ, Ali JM, Wlodek E, Negus MC, Harper IG, Chhabra M, et al. CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection. Proc Natl Acad Sci USA. 2015;112:12788–93. https://doi.org/10.1073/pnas.1513533112.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Murphy WJ, Kumar V, Bennett M. Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized. J Exp Med. 1987;166:1499–509. https://doi.org/10.1084/jem.166.5.1499.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rottman M, Soudais C, Vogt G, Renia L, Emile JF, Decaluwe H, et al. IFN-gamma mediates the rejection of haematopoietic stem cells in IFN-gammaR1-deficient hosts. PLoS Med. 2008;5:e26 https://doi.org/10.1371/journal.pmed.0050026.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Coley SM, Ford ML, Hanna SC, Wagener ME, Kirk AD, Larsen CP. IFN-gamma dictates allograft fate via opposing effects on the graft and on recipient CD8 T cell responses. J Immunol. 2009;182:225–33. https://doi.org/10.4049/jimmunol.182.1.225.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tjon JM, Langemeijer SMC, Halkes CJM. Anti thymocyte globulin-based treatment for acquired bone marrow failure in adults. Cells 2021;10. https://doi.org/10.3390/cells10112905.

  • Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD, Kurlander R, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361:2309–17. https://doi.org/10.1056/NEJMoa0904971.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sauzay C, Voutetakis K, Chatziioannou A, Chevet E, Avril T. CD90/Thy-1, a Cancer-associated cell surface signaling molecule. Front Cell Dev Biol. 2019;7:66. https://doi.org/10.3389/fcell.2019.00066.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Flurkey K, Currer JM, Harrison DE. Mouse models in aging research. The mouse in biomedical research 2nd Edition. 2007; 2023. https://doi.org/10.1016/B978-012369454-6/50074-1.

  • Jackson SJ, Andrews N, Ball D, Bellantuono I, Gray J, Hachoumi L, et al. Does age matter? The impact of rodent age on study outcomes. Lab Anim. 2017;51:160–9. https://doi.org/10.1177/0023677216653984.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Krishnarajah S, Ingelfinger F, Friebel E, Cansever D, Amorim A, Andreadou M, et al. Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice. Nat Aging. 2022;2:74–89. https://doi.org/10.1038/s43587-021-00148-x.

    Article 
    CAS 
    PubMed 

    Google Scholar