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Articles de revues sur le sujet « Treosulfan analog and chimerism »

Auteur : Grafiati

Publié le 7 juin 2025

Mis à jour le 2 août 2025

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1

Srinivas, G., D.V. Ramanjaneyulu, E. Muralinath, et al. "An Important Parameters of Hematopoietic Stem Cell Include Anatomy as Well as Physiology, Indications, Treatment, Complications and Clinical Significance." Research and Reviews: Journal of Holistic Nursing 2, no. 2 (2025): 1–11. https://doi.org/10.5281/zenodo.15356016.

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<em>Since the Sickle Cell Anemia Act, there has been a steady improvement in sickle cell disease screening and treatment. Although new medical treatments have been developed, sickle cell disease is still incurable for the majority of those affected, and the only cure for those who have sickle cell disease is hematopoietic stem cell transplantation. Autologous hematopoietic stem cell transplantation involves genetically modifying the patient's stem cells to correct the genetic mutation that causes sickle cell disease. Allogeneic hematopoietic stem cell transplantation replaces the damaged stem

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Slatter, Mary A., Kanchan Rao, Persis Amrolia, et al. "Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience." Blood 117, no. 16 (2011): 4367–75. http://dx.doi.org/10.1182/blood-2010-10-312082.

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Abstract Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan- or melphalan-based conditioning. Treosulfan causes less veno-occlusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children. Children received 42 g/m2 or 36 g/m2 with cyclophosphamide 200 mg/kg (n = 30) or fludarabine 150 mg/m2 (n = 40), with alemtuzumab in most. Median age at transplantation was 8.5 months (range, 1.2-175 months); 46 (66%) patients w

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Kalwak, Krzysztof, Monika Mielcarek, Katharine Patrick, et al. "Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies." Bone Marrow Transplantation 55, no. 10 (2020): 1996–2007. http://dx.doi.org/10.1038/s41409-020-0869-6.

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Abstract Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dos

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Nogai, Axel, Marc Thiele, Markus M. Heimesaat, Eckhard Thiel, Ulf B. Goebel, and Lutz Uharek. "Conditioning with Treosulfan and Cyclophosphamide without Application of Antibodies in MHC Mismatch Transplantations in Mice." Blood 108, no. 11 (2006): 5159. http://dx.doi.org/10.1182/blood.v108.11.5159.5159.

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Abstract BACKGROUND: Treosulfan is increasingly used in clinical conditioning regimens because of its myeloablative and immunosuppressive effects and the low hepatotoxicity compared to busulfane. The myeloablative and immunosuppressive characteristics of treosulfane was investigated in a murine MHC mismatch transplantation model. METHODS: C57BL/10 (H-2Db) female mice were treated with treosulfan (2000 mg/kg) on day -3 to -1 and increasing doses of cyclophosphamide (without, 100 or 200mg/kg) at day -1, or 3000 mg/kg treosulfan with and without 200 mg/kg cyclophosphamide at day -1. Some mice wer

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Slatter, Mary A., and Andrew R. Gennery. "Treosulfan-based conditioning for inborn errors of immunity." Therapeutic Advances in Hematology 12 (January 2021): 204062072110139. http://dx.doi.org/10.1177/20406207211013985.

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Inborn errors of immunity (IEI) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem-cell transplantation (HSCT) has increased rapidly with the advent of next-generation sequencing. The methods used to transplant children with IEI have improved dramatically over the last 20 years. The introduction of reduced-toxicity conditioning is an important factor in the improved outcome of HSCT. Treosulfan has myeloablative and immunosuppressive properties, enabling engraftment with less to

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Casper, Jochen, Wolfgang Knauf, Thomas Kiefer, et al. "Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation." Blood 103, no. 2 (2004): 725–31. http://dx.doi.org/10.1182/blood-2002-11-3615.

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Abstract New conditioning regimens are being explored to reduce toxicity and enable allogeneic bone marrow transplantation in patients not eligible for conventional transplantation. We have investigated treosulfan, an alkylating agent, with the aim of developing an efficient and reliable but less-toxic conditioning regimen. A series of 30 patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (n = 14) or unrelated (n = 16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenous

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Wojnar, Jerzy, Sebastian Giebel, Miroslaw Markiewicz, et al. "Treosulfan-Based Reduced Toxicity Regimen Prior to Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Disorders." Blood 108, no. 11 (2006): 5245. http://dx.doi.org/10.1182/blood.v108.11.5245.5245.

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Abstract Graft rejection is a major cause of failure after alloHCT in non-malignant hematopoietic disorders including severe aplastic anemia (SAA) and paroxysmal nocturnal hemaoglobinuria (PNH). For patients with high risk of this complication we introduced a novel conditioning regimens, based on treosulfan - an alkylating agent possesing both immuno- and myeloablative properties. Between 2003–2006, eleven patients (age: 23(14–35) years) with SAA (n=6) or PNH (n=5) were treated in a single institution with alloHSCT from either HLA-identical sibling (n=3) or an unrelated volunteer (n=8). For pa

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ten Brink, Marloes H., Robbert G. M. Bredius, Juliëtte Zwaveling, et al. "Treosulfan-Based Conditioning in Pediatric Hematopoietic Stem Cell Transplantation: A Prospective Study on Pharmacokinetics and Early Clinical Outcomes." Blood 124, no. 21 (2014): 3865. http://dx.doi.org/10.1182/blood.v124.21.3865.3865.

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Abstract Introduction Treosulfan is an alkylating agent which is increasing applied in regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in children. It has strong myeloablative and immunosuppressive activity and, in comparison with busulfan and total body irradiation, a relatively mild toxicity profile. The optimal dose of treosulfan in pediatric patients, remains to be established. To optimize the balance between treosulfan efficacy and toxicity, pharmacokinetic (PK) monitoring may be a valuable tool. With this purpose, we recently developed a PK and limited samplin

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Marzollo, Antonio, Elisabetta Calore, Manuela Tumino, et al. "Treosulfan-based conditioning regimen in sibling and alternative donor hematopoietic stem cell transplantation for children with sickle cell disease." Mediterranean Journal of Hematology and Infectious Diseases 9, no. 1 (2017): e2017014. http://dx.doi.org/10.4084/mjhid.2017.014.

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Background and objectives Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD) when employing the most frequently used Busulfan-based conditioning regimen. The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed.Methods We report our single-center experience: 11 patients with sickle cell disease received HSCT with a Treosulfan

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Suh, Jin Kyung, Ho Joon Im, Sung Han Kang, Hyery Kim, Eun Seok Choi, and Kyung-Nam Koh. "Successful Treatment Outcomes of Hematopoietic Stem Cell Transplantation with Reduced-Toxicity Conditioning Regimen Incorporating Treosulfan in Pediatric Patients with XIAP Deficiency." Blood 142, Supplement 1 (2023): 3922. http://dx.doi.org/10.1182/blood-2023-190661.

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Background X-linked inhibitor of apoptosis (XIAP) defciency is an inherited primary immunodefciency characterized by chronic infammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and infammatory bowel disease (IBD). Although hematopoietic stem celltransplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory. Methods We have performed HSCT with treosulfan based RTC regimen for pediatric patients with non-malignant disorders since January 2016, and reviewed the medical records of patients with XIAP deficiency

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Batsis, Ioannis, Ioanna Sakellari, Apostolia Papalexandri, et al. "Survival Advantage with Comparable Complete Chimerism Patterns in Reduced Toxicity Treosulfan-Based Vs Reduced Intensity Busulfan-Based Conditinioning Regimen in AML/MDS Patients Undergoing Allogeneic Haematopoietic Cell Transplantation." Blood 126, no. 23 (2015): 1914. http://dx.doi.org/10.1182/blood.v126.23.1914.1914.

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Abstract Introduction: The optimal regimen for patients not fitting criteria for myeloablative conditioning has not yet been established. Treosulfan-based conditioning emerges as a potent antileukemic regimen with high efficacy and low toxicity in acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) patients. The current prospective study was designed to explore both safety and efficacy of FluTreo (fludarabine 150mg/m2, treosulfan 14 gr/m2/d ×3d) in medically infirm patients. Furthermore, we compared the outcome with a control similar population treated with FluBuATG (fludarabine 150m

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Albert, Michael H., Mary A. Slatter, Andrew R. Gennery, et al. "Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis." Blood 139, no. 13 (2022): 2066–79. http://dx.doi.org/10.1182/blood.2021014687.

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Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 1

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Kalwak, Krzysztof, Peter Bader, Jan Styczynski, et al. "Prospective Clinical Phase II Results on Treosulfan-Based Conditioning Treatment of 70 Paediatric Patients with Haematological Malignancies." Blood 132, Supplement 1 (2018): 3354. http://dx.doi.org/10.1182/blood-2018-99-110980.

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Abstract Background Standard myeloablative conditioning treatment prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) of children is associated with a considerable risk of severe adverse events (AEs). Previous clinical studies in adults confirmed that treosulfan-based conditioning has myeloablative, immunosuppressive and anti-neoplastic effects associated with favorable non-relapse mortality (NRM). Therefore, treosulfan-based conditioning treatment was prospectively evaluated in pediatric patients with hematological malignancies within an extended clinical phase II trial. Pa

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Balashov, D. N., A. L. Laberko, E. R. Sultanova, et al. "The role of plerixafor in conditioning regimens before unmanipulated bone marrow transplantation in patients with Wiscott–Aldrich syndrome." Pediatric Hematology/Oncology and Immunopathology 22, no. 2 (2023): 12–15. http://dx.doi.org/10.24287/1726-1708-2023-22-2-12-15.

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Our previous experience of using plerixafor and granulocyte colony stimulating factor (G-CSF) in addition to treosulfan-based conditioning in patients with Wiscott–Aldrich syndrome (WAS) demonstrated efficacy and a decreased risk of severe graft failure after hematopoietic stem cell transplantation (HSCT) with TCRab + /CD19 + graft depletion. Because of the remaining risk of graft failure in WAS patients following HSCT with unmanipulated grafts reported in a number of large-scale retrospective studies, we used plerixafor and G-CSF in conditioning regimens in 6 WAS patients who received native

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Hilgendorf, Inken, Nils Winkelmann, Jochen J. Frietsch, et al. "Treosulfan, Fludarabine and Cytarabine As Conditioning before Allogeneic Hematopoietic Stem Cell Transplantation." Blood 132, Supplement 1 (2018): 5702. http://dx.doi.org/10.1182/blood-2018-99-118259.

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Abstract Background: The combination of treosulfan witth fludarabine was successfully introduced into toxicity-reduced conditioning regimens for hematopoietic stem cell transplantation (HCT). However, the risk of post-HCT relapse remains of concern. Here we report for the first time on the results of an individual treatment approach with treosulfan, fludarabin and cytarabine as conditioning for allogeneic HCT in patients with AML, MPN or MDS. Methods: 22 patients were treated with fludarabine 30 mg/m² given on day -6 to day -2, treosulfan 14 g/m² administered on days -4 to day -2 and cytarabin

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Veys, Paul. "Reduced intensity transplantation for primary immunodeficiency disorders." Pediatric Reports 3, no. 2s (2011): 11. http://dx.doi.org/10.4081/pr.2011.s2.e11.

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Studies so far indicate that reduced intensity transplantation (RIT) may have an important role in treating patients with primary immunodeficiency disease (PID). Unlike more standard approaches, such regimens can be used without severe toxicity in patients with severe pulmonary or hepatic disease. RIT also offers the advantage that long-term sequelae such as infertility or growth retardation may be avoided or reduced. RIT appears to be most appropriate for those patients with significant co-morbidities (eg T cell deficiencies) and those undergoing unrelated donor haematopoietic cell transplant

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Holowiecki, Jerzy, S. Giebel, D. Beelen, et al. "Phase II Multicenter Trial To Evaluate the Safety and Efficacy of Low-Toxicity Treosulfan/Fludarabine Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia." Blood 110, no. 11 (2007): 621. http://dx.doi.org/10.1182/blood.v110.11.621.621.

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Abstract BACKGROUND: The toxicity of commonly used myeloablative regimens is the main factor limiting applicability and restricting upper age limit for allogeneic hematopoietic stem cell transplantation (alloHSCT). However, reduced intensity conditioning (RIC) protocols are associated with high risk of relapse. Previous dose-escalation trials revealed high-dose treosulfan-based conditioning an alternative treatment with myeloablative as well as antileukemic potential, accompanied by low non-hematological toxicity. The goal of this multicenter phase II trial was to evaluate safety and efficacy

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Blau, I. W., Martin Schmidt-Hieber, N. Leschinger, et al. "Engraftment kinetics and hematopoietic chimerism after reduced-intensity conditioning with fludarabine and treosulfan before allogeneic stem cell transplantation." Annals of Hematology 86, no. 8 (2007): 583–89. http://dx.doi.org/10.1007/s00277-007-0294-6.

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Markiewicz, Miroslaw, Malwina Rybicka-Ramos, Monika Dzierzak-Mietla, et al. "Allo-HCT from MUD/MRD for Paroxysmal Nocturnal Hemoglobinuria - 12 Years of Experience." Blood 128, no. 22 (2016): 5886. http://dx.doi.org/10.1182/blood.v128.22.5886.5886.

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Abstract Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal abnormality of hematopoietic stem cell leading to lack of phosphatidylinositol glycoproteins, sensitizing cells to complement-mediated lysis. Despite the efficient symptomatic treatment of hemolytic PNH with eculizumab, allo-HCT is the only curative treatment for the disease, although outcomes presented in the past were controversial. Material and methods: We report 41 allo-HCTs: 37 from MUD and 4 from MRD performed for PNH in 2004-2016. Median age of recipients was 29(20-62) years and donors 30(19-53),

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Markiewicz, Miroslaw, Anna Koclega, Monika Dzierzak-Mietla, et al. "Allo-HSCT from MUD/MRD As a Curative Treatment in Paroxysmal Nocturnal Hemoglobinuria." Blood 124, no. 21 (2014): 1251. http://dx.doi.org/10.1182/blood.v124.21.1251.1251.

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Abstract Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal abnormality of the hematopoietic stem cell caused by somatic mutation in the phosphatidylinositol glycan-class A (PIG-A) gene located on the short arm of the X chromosome. Cells with lack phosphatidylinositol glycoproteins are more sensitive to complement-mediated lysis. Despite the efficient symptomatic treatment of hemolytic PNH with eculizumab, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment of the disease, although outcomes presented in the past were cont

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Andersson, Goran, Ben M. W. Illigens, Kevin W. Johnson, et al. "Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice." Blood 101, no. 11 (2003): 4305–12. http://dx.doi.org/10.1182/blood-2002-06-1649.

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Abstract Immunologic reactions against gene therapy products may prove to be a frequent problem in clinical gene therapy protocols. Enhanced green fluorescence protein (EGFP) is commonly used as a marker in gene transfer protocols, and immune responses against EGFP-expressing cells have been documented. The present study was designed to investigate the effect of a pharmacologic, nonmyeloablative, conditioning regimen on the development of EGFP+ donor/recipient mixed bone marrow chimerism and ensuing tolerance to EGFP-expressing transplants. To this end, C57BL/6J (B6) mice were treated with sol

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Abraham, Aby, Eunice Sindhuvi, Anu Korula, et al. "Donor Lymphocyte Infusion in Patients with Thalassemia Major Who Have Mixed Chimerism Following Allogeneic Stem Cell Transplant." Blood 126, no. 23 (2015): 1965. http://dx.doi.org/10.1182/blood.v126.23.1965.1965.

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Abstract Allogeneic stem cell transplantation (HSCT) is the only curative option for patients with thalassemia major (BTM). HSCT in BTM is associated with increased risk of graft rejection. Some patients do not achieve full donor chimerism after transplant despite hematopoietic engraftment. Early post transplant mixed chimerism (MC) is a known predictor of secondary graft rejection. Data is limited on the role of donor lymphocyte infusion (DLI) to prevent secondary graft rejection following detection of early MC in BTM. We report our experience with DLI in BTM patients who had developed progre

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Koroleva, D. A., N. G. Gabeeva, M. Yu Drokov, et al. "First experience of allogeneic haematopoietic stem cell transplantation in patients with mantle cell lymphoma with a mutation in the TP53 gene." Russian journal of hematology and transfusiology 65, no. 4 (2020): 483–500. http://dx.doi.org/10.35754/0234-5730-2020-65-4-483-500.

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Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.Aim. Efﬁcacy and safety assessment of allo-HSCT in MCL-TP53+ patients.Main ﬁndings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “ﬂudarabine + treosu

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PAI, Aswin Anand, John C. Panetta, Ezhil Pavai Mohanan, et al. "Treosulfan Metabolite (S, S-EBDM) Pharmacokinetics Influences Regimen Related Toxicity in Patients with Beta Thalassaemia Major Undergoing HSCT." Blood 134, Supplement_1 (2019): 1977. http://dx.doi.org/10.1182/blood-2019-125604.

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A toxicity reduced conditioning regimen containing Treosulfan (Treo), Fludarabine (Flu), Thiotepa in patients with class III high risk thalassemia major (TM) has significantly improved transplant outcomes compared to the historical Busulfan/cyclophosphamide based myeloablative regimen (Mathews et al, 2013). However, complications related to mixed chimerism, rejection and regimen related toxicity remain. Analysis of Treo pharmacokinetics (PK) in TM showed significant inter individual variation but no association with HSCT outcome (Mohanan et al, 2018). This may be attributed to the fact that on

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Holowiecki, Jerzy, Sebastian Giebel, Jerzy Wojnar, et al. "Treosulfan, Fludarabine, and Antithymocyte Globulin - A Low Toxicity Conditioning Regimen for Unrelated Donor - Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia." Blood 108, no. 11 (2006): 2948. http://dx.doi.org/10.1182/blood.v108.11.2948.2948.

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Abstract Unrelated donor - hematopoietic stem cell transplantation (URD-HSCT) is the treatment of proved long-term efficacy for chronic myeloid leukemia (CML) patients not having an HLA-identical sibling. However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome [Radich, Blood2003, 102, 31–5]. This is of increasing importance in the presence of challanging options offered by tyrosine kinase inhibitors. Between 2003–2006 we introduced a new preparetive regimen consisting of Treosulfan (a soluble alkylyting

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Mohanan, Ezhil Pavai, John C. Panetta, Shareen Stella Backia Royan, et al. "Population Pharmacokinetics of Fludarabine and Treosulfan in Patients with Thalassemia Undergoing Hematopoietic Stem Cell Transplantation." Blood 126, no. 23 (2015): 3120. http://dx.doi.org/10.1182/blood.v126.23.3120.3120.

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Abstract A toxicity reduced conditioning regimen containing Treosulfan (Treo), fludarabine (Flu), thiotepa for high risk Thal Major (TM) has been used since 2009 at our centre that has significantly improved transplant outcomes of these patients compared to the historical cohort of patients receiving busulfan/ cyclophosphamide based myeloablative regimen (Mathews et al, 2013). Limited knowledge is available on the pharmacokinetics (PK), pharmacogenetics (PG) and pharmacodynamics of fludarabine and treosulfan, especially in non-malignant hematological disorders like TM. We describe here the PK

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Ruutu, Tapani, Liisa Volin, Dietrich W. Beelen, et al. "Reduced Toxicity Conditioning with Treosulfan and Fludarabine in Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes: Results of an International Prospective Phase II Trial." Blood 112, no. 11 (2008): 3274. http://dx.doi.org/10.1182/blood.v112.11.3274.3274.

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Abstract Recent preclinical and clinical data have revealed treosulfan a promising alternative conditioning agent for allogeneic hematopoietic stem cell transplantation. After previous dose-finding studies in high-risk patients suffering from various hematological malignancies this prospective, multicenter phase II trial was carried out to assess the safety and efficacy of treosulfan-based conditioning in MDS patients. Eleven centers from four countries participated. Forty-five patients (24 females, 21 males) with a median age of 50 years (range 22 – 63 years) were included. In 33 % of the tra

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Troeger, Anja, Katharina Kleinschmidt, Tarek Hanafee-Alali та ін. "Treosulfan Based Haploidentical Αß T Cell Depleted HSCT Represents a Curative Alternative in Pediatric and Adult Patients with Transfusion Dependent Thalassaemia". Blood 142, Supplement 1 (2023): 2169. http://dx.doi.org/10.1182/blood-2023-189695.

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Background: Quality of life remains severely compromised in patients suffering from Transfusion Dependent Thalassemia (TDT) despite optimal supportive care. HSCT with a MSD, the current curative option, achieving a 92.1% 2y-OS in children and 84.4% in adults (EBMT registry). Unfortunately, availability of MDs is limited, so that haploidentical HSCT is increasingly explored. Methods: 13 TDT patients (median age: 11 years; range: 2-23) received either a CD3 +/CD19 + (n=4; all class II/III) or αß/CD19 + (n=10; 7 class II, II/III) T-haplo-HSCT and were compared with 8 TDT-patients (7 class II, II/

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Chichra, Akanksha, Lingaraj Nayak, Rushabh Kothari, et al. "Fludarabine Melphalan Versus Fludarabine Treosulfan As Reduced Intensity Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplant - a Retrospective Analysis." Blood 134, Supplement_1 (2019): 4493. http://dx.doi.org/10.1182/blood-2019-128099.

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Introduction Allogeneic hematopoietic stem cell transplantation (AHSCT) has evolved as a curative therapy for various hematological malignancies. Regimen-related toxicity and transplant-related mortality (TRM) preclude the use of myeloablative conditioning (MAC) regimens in older and unfit patients. Reduced intensity conditioning (RIC) regimens have enabled AHSCT in such patients. There is a recent rise in use of RIC regimens even in younger patients in view of decreased toxicity and equal efficacy as reported in some studies. Fludarabine + Melphalan (FM) and Fludarabine + Treosulfan (FT) are

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Gavriilaki, Eleni, Despina Mallouri, Grigorios Salvaras, et al. "Long-Term Safety and Efficacy of Treosulfan-Based Conditioning Regimens of Allogeneic Hematopoietic Cell Transplantation." Blood 144, Supplement 1 (2024): 3484. https://doi.org/10.1182/blood-2024-200317.

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Background: Treosulfan-based regimens have been widely used, with outcomes comparable to other myeloablative conditionings, even in older or frail patients. However, the long-term safety and efficacy of these regimens remain unknown. Methods: We prospectively studied consecutive patients that received allogeneic hematopoietic cell transplantation (alloHCT) in our JACIE-accredited center over the last decade with the conditioning regimen of FT14 (Fludarabine 150mg/m2-Treosulfan 42mg/m2). Post-transplant Cyclophosphamide was added in haploidentical donors and ATG (Thymoglobulin 5mg/kg) in patien

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Holowiecki, Jerzy, Sebastian Giebel, Jerzy Wojnar, et al. "Treosulfan + Fludarabine +/− Thymoglobulin - An Effective Low Toxicity Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia." Blood 106, no. 11 (2005): 5309. http://dx.doi.org/10.1182/blood.v106.11.5309.5309.

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Abstract Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only treatment of proved long-term efficacy in chronic myeloid leukemia (CML). However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome. Between 2003–2005 a phase II study was conducted to evaluate the feasibility of a new preparetive regimen consisting of Treosulfan (a soluble alkylyting agent) 14 g/m2/d. on days -6, -5, -4, Fludarabine 30 mg/m2/d on days -5, -4, -3, -2, -1, and, in case of unrelated donor transplants (URD-HSCT

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Holowiecki, Jerzy, Sebastian Giebel, Jerzy Wojnar, et al. "Treosulfan/Fludarabine - a Low Toxicity but Myeloablative Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia." Blood 104, no. 11 (2004): 1022. http://dx.doi.org/10.1182/blood.v104.11.1022.1022.

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Abstract Although allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only treatment of proved long-term efficacy in chronic myeloid leukemia (CML), high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome. In a series of 13 CML patients (age 35, range 16–52 years) we introduced a novel myeloablative conditioning regimen consisting of Treosulfan (alkylyting agent, soluble Busulfan-derivative) 14 g/m2/d. on days −6, −5, −4, Fludarabine 30 mg/m2/d on days −5, −4, −3, −2, −1, and, in case of unrelate

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Gassas, Adam, Farah O'Boyle, Shahzya Chaudhury, et al. "Complex Clonal Evolution Can Occur Following Transplantation for Transfusion Dependent Thalassaemia in the Context of Mixed Myeloid Chimerism and Reduced Conditioning Regimens." Blood 138, Supplement 1 (2021): 2906. http://dx.doi.org/10.1182/blood-2021-153519.

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Abstract Haemopoietic stem cell transplantation (HSCT) is a well-established treatment modality for the cure of transfusion dependent thalassaemia (TDT) and sickle cell disease (SCD). Clonal evolution has recently been identified as a concerning event in the setting of mixed chimerism and/or ineffective haemopoiesis following conventional bone marrow transplantation and gene therapy for haemoglobinopathies. This has so far been restricted to SCD only, with the presumption that despite both conditions sharing an ineffective erythropoietic marrow compartment, there may be inflammatory and hypoxi

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Lorusso, Alessandro, Roberto Crocchiolo, Carlo Messina, et al. "Full Dose Treosulfan Based Reduced Toxicity Conditioning Regimen in Allogeneic Stem Cell Transplantation: Results in 123 Patients." Blood 120, no. 21 (2012): 3139. http://dx.doi.org/10.1182/blood.v120.21.3139.3139.

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Abstract Abstract 3139 Conditioning in allogeneic stem cell transplantation has been widely explored in the last decades, since the introduction of the Reduced Intensity Conditioning (RIC) allowed the extension of the feasibility of allotransplants in previously ineligible patients. Outcome of both treatments remains comparable because of an higher incidence of relapse although reduction of Non Relapse Mortality (NRM) in RIC. Treosulfan is a bifunctional alkylating agent without major extra-haematological toxicities. Here we show the results of a Treosulfan based regimen in use at our Center i

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O'Boyle, Farah, Natalie Killeen, Mikel Valganon, et al. "Fludarabine/Treosulfan/Thiotepa/ATG Conditioning Leads to Earlier Engraftment and Higher Donor Chimerism Than Busulfan/Cyclophosphamide, and Enables the Use of Mismatched and Unrelated Donors for Transplantation in Haemoglobinopathies." Blood 120, no. 21 (2012): 3234. http://dx.doi.org/10.1182/blood.v120.21.3234.3234.

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Abstract Abstract 3234 Haemopoietic stem cell transplantation is the only proven curative treatment available for haemoglobinopathies. From 2000 to 2010 severty-four consecutive transplants were conditioned with busulfan 14 mg/kg, cyclophosphamide 200 mg/kg and alemtuzumab (Bu/Cy) achieving a DFS of 94.5%. In order to reduce busulfan toxicity, minimise mixed chimerism and enable the use of related mismatched and unrelated donors, the conditioning regimen was modified: fludarabine 160 mg/m2, treosulfan 42 g/m2, thiotepa 10 mg/kg and ATG (Thymoglobulin) 7.5 mg/kg or 11.25 mg/kg (FTTA). 18 patien

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Mehta, Pallavi, Aakanksha A. Singh, Neha Yadav, et al. "Busulfan (Bu) and Cyclophosphamide (Cy) Based Conditioning Regimen Still Holds the Promise of Being a Safe and Efficacious Regimen for Allogeneic Transplantation in Patients with Transfusion Dependent Thalassemia (TDT) Even in High Risk." Blood 138, Supplement 1 (2021): 949. http://dx.doi.org/10.1182/blood-2021-150358.

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Abstract Introduction: Allogeneic stem cell transplantation (HSCT) is a potential curative treatment for TDT. BuCy based regimen has been used widely as a standard myeloablative chemotherapy. However, the use of treosulfan based conditioning regimen has increased over the last decade (Choudhary D et al BBMT 2013). We analysed the safety and efficacy of BuCy based vs Treosulfan/Thiotepa/Fludrabine (Treo/Thio/Flu) regimens in TDT between September 2013 and March 2021. Method: This is an observational retrospective hospital record-based study approved by Institutional Review Board. Regimen used:

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Goncalves, Kevin A., Sharon L. Hyzy, Melissa L. Brooks, Hans J. Hertzler, Anthony E. Boitano, and Michael P. Cooke. "High Dose Hematopoietic Stem Cell Transplantation Leads to Rapid Hematopoietic and Microglia Recovery and Disease Correction in a Mouse Model of Hurler Syndrome." Blood 134, Supplement_1 (2019): 4424. http://dx.doi.org/10.1182/blood-2019-131189.

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Background . Allogeneic hematopoietic stem cell transplant (HSCT) is a promising approach to halt disease progression and prevent or ameliorate neurological symptoms arising from select inherited metabolic disorders (IMDs). Donor-derived cells, including microglia, limit disease progression post-HSCT via production of normal enzyme in a process called cross-correction. A standard cell dose used in HSCT is sub-optimal, resulting in delayed hematopoietic recovery and slower correction of central nervous system (CNS) defects (Lund et al BBMT 2019). To address these limitations, we developed MGTA-

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Federico, Vincenzo, Rosella Matera, Dalila Salvatore, et al. "Treosulfan Plus Fludarabine (TTF10) As Preparative Regimen before Haploidentical Trasplant in Elderly Patients with Acute Myeloid Leukemia." Blood 144, Supplement 1 (2024): 7294. https://doi.org/10.1182/blood-2024-208595.

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Introduction: Over the past few years an increasing number of elderly patients (pts) with AML has been considered eligible for allogenic transplantation (Allo-SCT). Post-transplant cyclophosphamide (PT-CY) has been confirmed to be effective and safe as graft-versus-host disase (GVHD) prophylaxis in the setting of haploidentical SCT (Haplo-SCT). In elderly patients (³ 65 years) this potentially curative option is often precluded by toxicity of myeloablative conditioning regimens. Treosulfan, a water soluble, bifunctional alkylating drug, showed strong myelotoxic, immunosuppressive, and antileuk

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Markiewicz, Miroslaw, Ewa Mendek-Czajkowska, Barbara Zupanska, Sebastian Giebel, and Slawomira Kyrcz-Krzemien. "The Favorable Outcome of Allo-HCT from MUD Following Treosulfan-Based Conditioning in Paroxysmal Nocturnal Hemoglobinuria." Blood 112, no. 11 (2008): 4420. http://dx.doi.org/10.1182/blood.v112.11.4420.4420.

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Abstract Although allo-HCT has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), experience with allo-HCT from matched unrelated donors (MUD) is limited and favorable conditioning treatment for PNH has not been established. We report results of 8 allo-HCTs from MUD (matched in HLA-A,B,C,DR,DQ alleles) performed for PNH with treosulfan-based conditioning in years 2004–2008 in Katowice, Poland. Median age of recipients was 27 years (range 20–35) and donors 33(28–43), median time from diagnosis to transplantation was 20(15–36) months. Median size of PNH clone was 90% gr

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Dadi, Gal, Amos Toren та Arnon Nagler. "Haploidentical STEM-Cell Transplantation for Children with ACUTE Leukemia and NON-Malignant Disorders, Using ΑΒ + T Cell /CD19 + B-Cell Depletion, a Single Center Experience". Blood 142, Supplement 1 (2023): 6780. http://dx.doi.org/10.1182/blood-2023-188199.

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Background: αβ+ T cells/CD19+ B cells depleted haploidentical Hematopoietic stem cell transplantation (αβ+ TCR/ CD19+ depleted haplo-HSCT) is increasingly used in children with acute leukemia (AL) and many non-malignant disorders (NMD) such as severe combined immune deficiency (SCID), inborn errors of immunity (IEI), bone marrow failure (BMF, acquired/congenital) and familial Hemophagocytic lymphohistiocytosis (HLH), in need of a transplant and not having a matched related donor. Within this heterogenous group of patients, it is important to try to define introductory requirements for successf

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Koch, Ute, and Robert Korngold. "A Synthetic CD4-CDR3 Peptide Analog Enhances Bone Marrow Engraftment Across Major Histocompatibility Barriers." Blood 89, no. 8 (1997): 2880–90. http://dx.doi.org/10.1182/blood.v89.8.2880.

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Abstract The efficacy of a synthetic peptide analog mimicking the CDR3-D1 domain of the CD4 molecule was investigated in murine models of allogeneic bone marrow engraftment after transplantation across major histocompatibility complex (MHC) barriers. A single dose of a CD4-CDR3 peptide analog was administered at the time of marrow transplantation to three different allogeneic mouse strain combinations after appropriate sublethal total body irradiation: (1) B10.BR → C57BL/6J (B6), a full allogeneic MHC difference; (2) (B6xDBA/2)F1 → (B6xCBA)F1 , a haploidentical MHC combination; and (3) B6.C-H2

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Wachowiak, Jacek, Alicja Chybicka, Jerzy Kowalczyk, et al. "Treosulfan-Based Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Increased Risk of Conventional Regimen Toxicity." Blood 106, no. 11 (2005): 1761. http://dx.doi.org/10.1182/blood.v106.11.1761.1761.

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Abstract It was investigated whether in children demonstrating high risk of toxicity related to conventional preparative regimens (prep-reg) for allo-HSCT, the prep-reg based on Treosulfan (TREO) (Feit, Rastrup-Andersen, 1970) enables to avoid severe toxic complications without increased incidence of graft failure and/or relapse. From July 2000 to April 2005 the TREO-based prep-reg was used prior to allo-HSCT in 43 children with increased risk of severe Busulfan- and FTBI-based regimens related toxicity (RRT) and/or non-compliance. In 37 patients (pts) allo-HSCT was performed for, usually adva

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Albert, Michael H., Mehtap Sirin, Manfred Hoenig, et al. "Salvage HLA-haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for graft failure in non-malignant disorders." Bone Marrow Transplantation 56, no. 9 (2021): 2248–58. http://dx.doi.org/10.1038/s41409-021-01323-9.

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AbstractGraft failure requires urgent salvage HSCT, but there is no universally accepted approach for this situation. We investigated T-cell replete haploidentical HSCT with post-transplantation cyclophosphamide following serotherapy-based, radiation-free, reduced intensity conditioning in children with non-malignant disorders who had rejected their primary graft. Twelve patients with primary or secondary graft failure received T-cell replete bone marrow grafts from haploidentical donors and post-transplantation cyclophosphamide. The recommended conditioning regimen comprised rituximab 375 mg/

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George, Biju, Auro Viswabandya, Aby Abraham, et al. "Increased Incidence of Mixed Chimerism with the Use of Fludarabine – Treosulfan Based Conditioning in Patients Undergoing Allogeneic Stem Cell Transplantation for Thalassaemia Major." Biology of Blood and Marrow Transplantation 21, no. 2 (2015): S284—S285. http://dx.doi.org/10.1016/j.bbmt.2014.11.451.

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Ploemacher, Rob E., Kevin W. Johnson, Elwin J. C. Rombouts, et al. "Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic bone marrow transplant model." Biology of Blood and Marrow Transplantation 10, no. 4 (2004): 236–45. http://dx.doi.org/10.1016/j.bbmt.2003.11.004.

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Markiewicz, Miroslaw, Monika Dzierzak-Mietla, Katarzyna Wisniewska-Piaty, et al. "The Favorable Results of Allo-HSCT in TKI-Resistant CML,." Blood 118, no. 21 (2011): 4145. http://dx.doi.org/10.1182/blood.v118.21.4145.4145.

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Abstract Abstract 4145 Introduction: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, for patients who fail TKI or progress to advanced phase disease, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapeutic option. The rationale of this study was to evaluate results of allo-HSCT in CML patients who have failed TKI treatment. Patients and Methods: 48 CML pts aged 33 (19–52) years who failed previous treatment with TKI (imatinib-37 pts, imatinib+dasatinib-5, imatinib+dasatinib+nilotinib- 3, dasatini

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Albert, Michael H., Mary Slatter, Andrew Gennery, et al. "Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen in Patients with Wiskott-Aldrich Syndrome Given Allogeneic Hematopoietic Cell Transplantation — an EBMT Inborn Errors Working Party and Scetide Retrospective Analysis." Blood 132, Supplement 1 (2018): 2175. http://dx.doi.org/10.1182/blood-2018-99-112394.

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Abstract PV and AL contributed equally Multiple studies from the EBMT registry and others have shown excellent survival rates after allogeneic haematopoietic stem cell transplantation (HSCT)for Wiskott-Aldrich syndrome (WAS) patients (Ozsahin et al, Blood 2008). The importance of myeloid engraftment for full disease correction has also been demonstrated (Moratto et al, Blood 2011). However, the vast majority of HSCTs in these studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. In 2005, the inborn errors working party (IEWP) of

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Rossi, Stefano, Giulia Baresi, Elena Soncini, et al. "Abstract 17: IL10R Deficiency and Hemopoietic Cell Transplantation (HCT): Outcome of 2 Patients Treated in a Single Center with CBU HCT." Stem Cells Translational Medicine 13, Supplement_1 (2024): S19. http://dx.doi.org/10.1093/stcltm/szae062.017.

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Abstract Introduction IL10R deficiency is a congenital cause of very-early onset inflammatory bowel disease (VEO-IBD). Therapeutic strategie immunosuppressive agents, surgery and hemopoietic cell transplantation (HCT). Objectives We report on two patients (one male and one female) affected with IL10R deficiency successfully treated with HCT. Methods We report on two patients (one male and one female) affected with IL10R deficiency successfully treated with HCT. Results The first patient is a Moroccan male that presented with failure to thrive and diarrhea few weeks after birth. Histologic asse

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Beier, Rita, Daniel Kotlarz, Kaan Boztug, et al. "Successful Allogeneic Hematopoietic Stem Cell Transplantation for Severe Inflammatory Bowel Disease – IL10 Receptor Deficiency May Serve as a Novel Therapeutic Paradigm." Blood 116, no. 21 (2010): 2379. http://dx.doi.org/10.1182/blood.v116.21.2379.2379.

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Abstract Abstract 2379 Inflammatory bowel diseases (IBDs) comprise a heterogeneous group of disorders, classically defined as Crohn's disease, ulcerative colitis, and indeterminate colitis. The molecular pathophysiology of enterocolitis is still largely unknown. Recently, we identified monogenic mutations in the IL10 receptor genes, providing novel insights into the role of IL10-mediated immune homeostasis in the human gut. Here, we report a series of 8 patients with mutations in the IL10RA or IL10RB gene. All patients presented within the first three months of life with severe enterocolitis a

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Nickel, Robert Sheppard, KY Chiang, Steven J. Hardy, et al. "Nonmyeloablative HLA-Identical Sibling Donor Transplantation for Children and Young Adults with Sickle Cell Disease: Interim Results of the SUN Multicenter Phase II Trial." Blood 138, Supplement 1 (2021): 1799. http://dx.doi.org/10.1182/blood-2021-144454.

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Abstract Background: HLA-identical sibling hematopoietic stem cell transplant (HSCT) using myeloablative chemotherapy conditioning is a proven cure for sickle cell disease (SCD), but is associated with serious short and long-term toxicities. Additionally graft versus host disease (GVHD) can complicate care post-HSCT and contribute to mortality. Given these concerns many pediatric hematologists and families are reluctant to pursue HSCT for SCD. Nonmyeloablative HSCT resulting in stable mixed chimerism has been demonstrated to abrogate the SCD phenotype in adults. Data on outcomes of this approa

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