Medium-dose etoposide, cyclophosphamide and total body irradiation conditioning potentiates anti-leukemia immunity in adults with acute lymphoblastic leukemia without aggravating graft-versus-host disease

Imamura, 2015, Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning, Exp Hematol Oncol, 4, 20, 10.1186/s40164-015-0015-0 Blume, 1987, Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies, Blood, 69, 1015, 10.1182/blood.V69.4.1015.1015 Schmitz, 1988, Fractionated total body irradiation and high-dose VP16-213 followed by allogeneic bone marrow transplantation in advanced leukemias, Blood, 72, 1567, 10.1182/blood.V72.5.1567.1567 Petersen, 1992, Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study, Bone Marrow Transplant, 10, 83 Blume, 1993, A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparative regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group Study, Blood, 81, 2187, 10.1182/blood.V81.8.2187.2187 Snyder, 1993, Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission, Blood, 82, 2920, 10.1182/blood.V82.9.2920.2920 Spitzer, 1994, Etoposide in combination with cyclophosphamide and total body irradiation or busulfan as conditioning for marrow transplantation in adults and children, Int J Radiat Oncol Biol Phys, 29, 39, 10.1016/0360-3016(94)90224-0 Mengarelli, 2002, Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia, Haematologica, 87, 52 Hunault, 2004, Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial, Blood, 104, 3028, 10.1182/blood-2003-10-3560 Jaxel, 1988, Topoisomerase inhibitors induce irreversible fragmentation of replicated DNA in concanavalin A stimulated splenocytes, Biochemistry, 27, 95, 10.1021/bi00401a016 Kaufman, 1989, Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, Camptotecin, and other anticancer drugs: a cautionary note, Cancer Res, 49, 5870 Berger, 1991, Etoposide (VP-16-213)-induced gene alteration: potential contribution to cell death, Proc Natl Acad Sci USA, 88, 8740, 10.1073/pnas.88.19.8740 Imamura, 1994, Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels, Int J Hematol, 60, 85 Toubai, 2004, Efficacy of etoposide, cyclophosphamide, and total body irradiation in allogeneic bone marrow transplantation for adult patients with hematological malignancies, Clin Transplant, 18, 552, 10.1111/j.1399-0012.2004.00225.x Shigematsu, 2008, Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total-body irradiation for adult patients with acute lymphoblastic leukemia, Biol Blood Marrow Transplant, 14, 568, 10.1016/j.bbmt.2008.02.018 Shigematsu, 2015, A safety and efficacy of medium-dose etoposide, cyclophosphamide and TBI before allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia, Transplant Direct, 1, 1, 10.1097/TXD.0000000000000514 Shigematsu, 2011, Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia, Int J Hematol, 94, 463, 10.1007/s12185-011-0944-2 Arai, 2017, Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults, Am J Hematol, 93, 47, 10.1002/ajh.24933 Harada, 2022, Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults, Cytotherapy, 24, 954, 10.1016/j.jcyt.2022.03.004 Morita-Fujita, 2022, Adult patients with Ph+ ALL benefit from conditioning regimen of medium-dose VP16 plus CY/TBI, Hematol Oncol, 40, 1041, 10.1002/hon.3046 Johnson, 2013, Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis, J Immunol, 192, 84, 10.4049/jimmunol.1302282 McNally, 2014, Eliminating encephalitogenic T cells without undermining protective immunity, J Immunol, 192, 73, 10.4049/jimmunol.1301891 Rios, 2019, Dramatic response of nivolumab-associated psoriasiform dermatitis to etoposide, Eur J Cancer, 107, 97, 10.1016/j.ejca.2018.11.025 Slater, 1991, Development of cyclosporine A mediated immunity in L1210 leukemia, Br J Cancer, 64, 1098, 10.1038/bjc.1991.471 Salter, 1995, Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD8-T lymphocytes, Clin Immunol Immunopathol, 75, 239, 10.1006/clin.1995.1077 Salter, 2001, Etoposide induction of tumor immunity in Lewis lung cancer, Cancer Chemother Pharmacol, 48, 327, 10.1007/s002800100357 Wan, 2012, Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells, PLoS One, 7, e32542, 10.1371/journal.pone.0032542 Bailly, 2020, Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times, NAR Cancer, 2, zcaa002, 10.1093/narcan/zcaa002 Tazawa, 2016, Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose etoposide, cyclophosphamide and total body irradiation regimen before allogeneic hematopoietic stem cell transplantation, J Pharm Health Care Sci, 2, 18, 10.1186/s40780-016-0052-9 Miura, 2006, Analysis of donor-type chimerism in lineage-specific cell populations after allogeneic myeloablative and nonmyeloablative stem cell transplantation, Bone Marrow Transplant, 37, 837, 10.1038/sj.bmt.1705352 Sugita, 2008, Influence of conditioning regimens and stem cell sources on donor-type chimerism early after stem cell transplantation, Ann Hematol, 87, 1003, 10.1007/s00277-008-0542-4 Chang, 1985, Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cells line (HL-60) demonstrated by computer analysis, Cancer Res, 45, 243 Usami, 1998, Role of tyrosine phosphorylation in etoposide-induced apoptosis and NF-κB activation, Biochem Pharmacol, 55, 185, 10.1016/S0006-2952(97)00429-2 Matsuoka, 1993, Transcription factors NF-IL6 and NF-κB synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8, Proc Natl Acad Sci USA, 90, 10193, 10.1073/pnas.90.21.10193 Mühl, 1999, Expression and release of chemokines associated with apoptotic cell death in human promonocytic U937 cells and peripheral blood mononuclear cells, Eur J Immunol, 29, 3225, 10.1002/(SICI)1521-4141(199910)29:10<3225::AID-IMMU3225>3.0.CO;2-0 Sun, 2002, NF-kappaB activation and inhibition: a review, Shock, 18, 99, 10.1097/00024382-200208000-00001 Kerbel, 2004, The anti-angiogenic basis of metronomic chemotherapy, Nat Rev Cancer, 4, 423, 10.1038/nrc1369 Henry, 1999, Antigen-presenting cells that phagocytose apoptotic tumor-derived cells are potent tumor vaccines, Cancer Res, 59, 3329 Garg, 2013, Cancer immunogenicity, danger signals, and DAMPs: What, when, and how?, Biofactors, 39, 355, 10.1002/biof.1125 Obeid, 2007, Calreticulin exposure dictates the immunogenicity of cancer cell death, Nat Med, 13, 54, 10.1038/nm1523 Feng, 2002, Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells, Blood, 100, 4108, 10.1182/blood-2002-05-1389 Srivastava, 1998, Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world, Immunity, 8, 657, 10.1016/S1074-7613(00)80570-1 Ma, 2013, ATP-dependent recruitment, survival and differentiation of dendritic cell precursors in the tumor bed after anticancer chemotherapy, Oncoimmunology, 2, e24568, 10.4161/onci.24568 Elliott, 2009, Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance, Nature, 461, 282, 10.1038/nature08296 Cirone, 2012, Activation of dendritic cells by tumor cell death, Oncoimmunology, 1, 1218, 10.4161/onci.20428 Krysko, 2012, Immunogenic cell death and DAMPs in cancer therapy, Nat Rev Cancer, 12, 860, 10.1038/nrc3380 Ohtsukasa, 2003, Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs, J Cancer Res Clin Oncol, 129, 719, 10.1007/s00432-003-0492-0 Fonsatti, 2007, Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2′-deoxycytidine in cutaneous melanoma: immunotherapeutic implications, Clin Cancer Res, 13, 3333, 10.1158/1078-0432.CCR-06-3091 Vignali, 2008, How regulatory cells work, Nat Rev Immunol, 8, 523, 10.1038/nri2343 Zamora, 2019, Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses, Sci Transl Med, 11, eaat8549, 10.1126/scitranslmed.aat8549 van Denderen, 1990, Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia, Blood, 76, 136, 10.1182/blood.V76.1.136.136 Schwab, 2018, Advances in B-cell precursor acute lymphoblastic leukemia genomics, Hemasphere, 2, e53, 10.1097/HS9.0000000000000053 Inoue, 2003, The kinetics of immune reconstitution after cord blood transplantation and selected CD34+ stem cell transplantation in children: comparison with bone marrow transplantation, Int J Hematol, 77, 399, 10.1007/BF02982652 Komanduri, 2007, Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing, Blood, 110, 4543, 10.1182/blood-2007-05-092130 Lucchini, 2015, Immune reconstitution after cord blood transplantation: peculiarities, clinical implications and management strategies, Cytotherapy, 17, 711, 10.1016/j.jcyt.2015.03.614 Iacobucci, 2017, Genetic basis of acute lymphoblastic leukemia, J Clin Oncol, 35, 975, 10.1200/JCO.2016.70.7836 Biernacki, 2020, Neoantigens in hematologic malignancies, Front Immunol, 11, 121, 10.3389/fimmu.2020.00121 Naik, 2022, Donor-derived multiple leukemia antigen-specific T-cell therapy to prevent relapse after transplantation in patients with ALL, Blood, 139, 2706, 10.1182/blood.2021014648 Kirshan, 1985, Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts, J Cell Biol, 66, 521, 10.1083/jcb.66.3.521 Misra, 1975, Inhibition by 4’-demethyl-epipodophyllotoxin 9-(4,6-C glucopyranoside) of human lymphoblasts cultures in G2 phase of the cell cycle, Cancer Res, 35, 99 Joel, 1994, Schedule-dependent topoisomerase II-inhibiting drugs, Cancer Chemother Pharmacol, 34, S84, 10.1007/BF00684869 Hande, 1996, The importance of drug scheduling in cancer chemotherapy. Etoposide as an example, Oncologist, 1, 234, 10.1634/theoncologist.1-4-234 Slevin, 1989, A randomized trial to evaluate the effect of schedule on the activity of etoposide in small cell lung cancer, J Clin Oncol, 7, 1333, 10.1200/JCO.1989.7.9.1333 Clark, 1994, A randomized trial of two etoposide schedules in small cell lung cancer: The influence of pharmacokinetics on efficacy and toxicity, J Clin Oncol, 12, 1427, 10.1200/JCO.1994.12.7.1427 Thompson, 1993, Prolonged administration of low-dose infusional etoposide in patients with etoposide sensitive neoplasms: A phase I/II study, J Clin Oncol, 11, 1322, 10.1200/JCO.1993.11.7.1322 Kunitoh, 1994, A phase I/II and pharmacologic study of long-term continuous infusion etoposide combined with cisplatin in patients with lung cancer, J Clin Oncol, 12, 83, 10.1200/JCO.1994.12.1.83 Pasquier, 2010, Metronomic chemotherapy: new rationale for new directions, Nat Rev Clin Oncol, 7, 455, 10.1038/nrclinonc.2010.82 Ghobaldi, 2022, The role of allogeneic transplant for adult Ph+ ALL in CR1 with complete molecular remission: a retrospective analysis, Blood, 140, 2102 Jabbour, 2022, Treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia- from intensive chemotherapy combinations to chemotherapy-free regimens. A review, JAMA Oncol, 8, 1340, 10.1001/jamaoncol.2022.2398 Jabbour, 2023, Ponatinib and blinatumomab for Philadelphia chromosome positive acute lymphoblastic leukemia: a US, single-centre, single-arm, phase 2 trial, Lancet Haematol, 10, e24, 10.1016/S2352-3026(22)00319-2 Zhang, 2023, Busulfan plus cyclophosphamide versus total body irradiation plus cyclophosphamide for adults acute B lymphoblastic leukemia: an open-label, multicenter, phase III trial, J Clin Oncol, 41, 343, 10.1200/JCO.22.00767