Grafapex (treosulfan) / Medac, Medexus - LARVOL DELTA

Incidence of Veno-Occlusive Disease in Patients with Neuroblastoma Treated with Autologous Stem Cell Transplantation After Chemoimmunotherapy with Temozolomide, Irinotecan, and Dinutuximab Beta. (PubMed, Cancers (Basel)) - "Six patients underwent HDC with ASCT according to the SIOPEN protocol (Busulfan and Melphalan (BuMel)). Treosulfan and Melphalan (TreoMel) were used in 13 patients...The incidence of severe VOD/SOS after ChIt and subsequent BuMel was higher than expected, with severe course resulting in two deaths. Taking into account the possible increase in the risk of VOD/SOS after BuMel used after chemotherapy combined with DB, careful observation with early VOD/SOS treatment in patients after ChIt is recommended and TreoMel regimen may be considered as less toxic."

Journal • Neuroblastoma • Oncology • Otorhinolaryngology • Solid Tumor • Transplantation

Ring Gantry Linear Accelerator Based Total Lymphoid Irradiation (TLI) Based Myeloablative Conditioning Regimen in Hematopoietic Stem Cell Transplant (HSCT) in Thalassemia: A Single Institute Experience (ASTRO 2026) - "Materials/ This is a single centre retrospective study of children who underwent hematopoietic stem cell transplantation (HSCT) using a uniform conditioning with single fraction TLI, Antithymocyte globulin, Cyclophosphamide, Fludarabine, Treosulfan and Thiotepa. TLI-based conditioning demonstrates a favorable tolerability, limited treatment related toxicity and should be included in haploidentical HSCT to ensure engraftment will full donor chimerism in children with TDT Thalassaemia."

Breast Cancer • Hematological Malignancies • Oncology • Solid Tumor

Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: Evolving Indications, Conditioning Strategies, and Outcomes. (PubMed, Hematol Rep) - " This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa-treosulfan-fludarabine (TTF) regimen. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies."

Journal • Review • Bone Marrow Transplantation • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Transplantation

Moderate Incidence but Striking Correlation with TBI of Secondary Malignancies after HSCT in Children with ALL: Long-Term Follow-up from the Prospective International BFM- and Forum-Trials (ASH 2023) - "Only pts with contraindications for TBI received chemo-conditioning, which consisted of i.v. busulfan, cyclophosphamide and etoposide. In the FORUM trial pts >4y of age were randomized to receive either TBI- or chemo-based conditioning regimens; pts 2 y of age at HSCT (94%, n=2024). TBI-based conditioning was applied in 64% (n=1429), while 34% (n=722) of pts received chemo-conditioning."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Basal Cell Carcinoma • Bone Marrow Transplantation • Brain Cancer • Breast Cancer • Chronic Graft versus Host Disease • CNS Tumor • Endocrine Cancer • Glioblastoma • Graft versus Host Disease • Hematological Malignancies • Leukemia • Non-melanoma Skin Cancer • Oncology • Pediatrics • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma • Transplantation • TP53

FORUM: Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia (clinicaltrials.gov) - P2/3 | N=1800 | Recruiting | Sponsor: St. Anna Kinderkrebsforschung | Trial primary completion date: Jun 2025 ➔ Jun 2030

Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: Heinrich-Heine University, Duesseldorf | Trial completion date: Jan 2028 ➔ Apr 2029 | Trial primary completion date: Jan 2026 ➔ Apr 2029

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • DEK • IDH1 • IDH2 • KMT2A • KRAS • NF1 • NRAS • NUP214 • PTPN11 • RIT1 • RUNX1 • TP53

Late Endocrine and Organ Toxicities After Treosulfan-Based Conditioning in Pediatric Hematopoietic Cell Transplantation: A Systematic Review. (PubMed, Pediatr Blood Cancer) - "In conclusion, treosulfan-based conditioning appears to have a meaningfully lower risk to gonadal dysfunction compared to busulfan, most prominently in patients with nonmalignant diagnoses and in females. No significant differences were observed for non-gonadal late effects, albeit data remain limited."

Journal • Review • Bone Marrow Transplantation • Infertility • Pediatrics • Sexual Disorders • Transplantation

SAFETY AND EFFICACY OF FLUDARABINE PLUS MYELOABLATIVE DOSE OF TREOSULFAN (FT14) CONDITIONING REGIMEN FOR AML – INTERIM ANALYSIS FROM THE FT14 STUDY GROUP (EBMT 2025) - "While busulfan-based regimens such as fludarabine-busulfan (FB4) are widely regarded as the gold standard for reduced-toxicity myeloablative conditioning, they are associated with risks such as Veno-Occlusive Disease (VOD), pulmonary toxicity, and high Transplant-Related Mortality (TRM)...Graft sources included peripheral blood stem cells or bone marrow, with Graft-versus-Host Disease (GvHD) prophylaxis using ATG (Thymoglobulin or Grafalon), cyclosporine and short course methotrexate...On viral point of view, 6% experienced CMV reactivation despite letermovir prophylaxis, 11% had detectable EBV viraemia (with no case of post-transplant lymphoproliferative disease), 4% had SARS-CoV-2 and 2% HHV6 reactivation... FT14 is a safe and effective myeloablative conditioning regimen for AML, demonstrating excellent disease control with minimal toxicity. Its reduced transplant-related mortality(TRM) and GvHD rates make it particularly beneficial for patients at high risk of..."

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hepatology • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Favourable Outcome after Treosulfan Based Conditioning in Patients Undergoing an Allogeneic Hematopoietic Cell Transplantation (alloHCT) for the Treatment of Acute Myleloid Leukaemia (AML): A Subgroup Analysis of the Randomized Phase III MC-Fludt.14/L Trial (TCT-ASTCT-CIBMTR 2022) - P3 | ", Lancet Haematol 2020) prospectively investigated whether a conditioning regimen with treosulfan/fludarabine (FT10) provides an outcome advantage after allogeneic HCT in elderly and/or comorbid AML and MDS patients when compared to the reduced-intensity conditioning regimen with busulfan/fludarabine (FB2). This analysis demonstrated superiority for FT10 especially in AML patients with HCT-CI > 2. Overall, the AML subgroup analysis demonstrated a clinically relevant benefit for the new treosulfan conditioning regimen in elderly and/or comorbid AML patients."

Clinical • P3 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

COMPARABLE OUTCOMES AFTER BUSULFAN- OR TREOSULFAN-BASED CONDITIONING FOR ALLO-HSCT IN CHILDREN WITH ALL-RESULTS OF FORUM. (PubMed, Blood Adv) - P2/3 | "Outcomes for CR1 or CR2 patients were similar irrespective of the regimen used. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for ALL patients > 4 years with contraindications or lack of access to TBI."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hepatology • Immunology • Transplantation

Pediatric Nonmalignant Hematopoietic Cell Transplantation in the Era of Precision Conditioning and Gene Therapy. (PubMed, Pediatr Ann) - "Fludarabine-based platforms combined with busulfan, melphalan, or treosulfan support durable engraftment with reduced toxicity, while matched unrelated, haploidentical, and cord blood donors expand access. For pediatricians, early referral before irreversible complications is critical. This review proposes a five-axis framework to guide referral, treatment selection, and survivorship planning."

Journal • Review • Aplastic Anemia • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Metabolic Disorders • Pediatrics • Primary Immunodeficiency • Rare Diseases • Sickle Cell Disease • Transplantation

RELEVANT: Evaluation of Treosulfan Versus Melphalan Conditioning Followed by PTCy in Patients With AML and MDS Undergoing Allogeneic Transplantation (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: Technische Universitt Dresden | Trial completion date: Dec 2028 ➔ Sep 2029 | Trial primary completion date: Dec 2028 ➔ Sep 2029 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Mitigating HLA Disparity in AML Transplantation: Comparable Outcomes After Haploidentical and 9/10 Mismatched Unrelated Donor Transplantation With Treosulfan and PTCy. (PubMed, Am J Hematol) - "Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative strategy for acute myeloid leukemia (AML), but the impact of HLA disparity in the era of posttransplant cyclophosphamide (PTCy) and reduced-toxicity conditioning remains unclear. Increasing age adversely affected outcomes, while Karnofsky performance status ≥ 90 and reduced-intensity conditioning were associated with improved survival. These findings suggest that, within a treosulfan-PTCy platform, major transplant outcomes are comparable between donor types, although haploidentical transplantation was associated with a higher incidence of chronic GVHD."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Treosulfan or busulfan plus clofarabine as reduced intensity conditioning regimen before allotransplant for adults with myeloid malignancies. (PubMed, Bone Marrow Transplant) - "CloT3 was independently associated with improved OS (p = 0.038), DFS (p = 0.026) and lower RI (p = 0.024). These exploratory results support further prospective studies, particularly in AML patients."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Dose-range Finding Treosulfan-based Conditioning (clinicaltrials.gov) - P1/2 | N=56 | Completed | Sponsor: medac GmbH | Phase classification: P2 ➔ P1/2

Phase classification • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=23 | Terminated | Sponsor: Fred Hutchinson Cancer Center | Active, not recruiting ➔ Terminated; The study was closed due to the end of funding.

Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

Expanding the conditioning armamentarium in adult acute lymphoblastic leukaemia: is treosulfan ready to challenge total body irradiation? (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Tailored conditioning for hematopoietic stem cell transplantation in children with Mendelian susceptibility to mycobacterial disease: A tale of two pathways for IFN-γ and IL-12 defects. (PubMed, J Hum Immun) - "IL-12-deficient cases engrafted well with fludarabine/treosulfan-based conditioning, whereas IFN-γ-deficient cases fared better with fludarabine/treosulfan/thiotepa-based conditioning due to a higher rejection risk...Cytomegalovirus reactivation occurred in four cases, which responded to ganciclovir or cidofovir...HSCT is a curative option for children with MSMD. However, we need to understand gene mutation and individualize the approach to preparation and conditioning regimens to help optimize the outcome."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • CNS Disorders • Cytomegalovirus Infection • Endocrine Disorders • Epilepsy • Graft versus Host Disease • Immunology • Infectious Disease • Transplant Rejection • Transplantation • IFNG • IL12A

Allogenic Hematopoietic Stem Cell Transplantation in Children With Transfusion Dependent Thalassemia Using Treosulfan-Thiotepa-Fludarabine Based Conditioning. (PubMed, J Pediatr Hematol Oncol) - "TTF conditioning with a peripheral blood stem cell graft is a well-tolerated and effective approach for allogeneic HSCT in thalassemia. It demonstrates reduced toxicity and favorable transplant outcomes, with superior results in the matched family donor setting compared with the alternate donor group, supporting its role as a promising alternative to traditional busulfan-based conditioning regimens."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Cytomegalovirus Infection • Genetic Disorders • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

Novel pathological genetic variant associated with DOCK8 deficiency: case report with successful hematopoietic stem cell transplantation. (PubMed, Allergol Immunopathol (Madr)) - "The patient underwent successful HSCT from a fully matched (10/10) HLA-compatible donor following conditioning with fludarabine and treosulfan. At 1 year follow-up, full donor chimerism was achieved, and the patient remained in remission. This case highlights a novel pathogenic variant in DOCK8 deficiency and demonstrates curative success following definitive diagnosis and timely HSCT."

Journal • Atopic Dermatitis • Bone Marrow Transplantation • Dermatitis • Dermatology • Immunology • Infectious Disease • Primary Immunodeficiency • Respiratory Diseases • Transplantation • DOCK8

Alternative Conditioning Regimens for Hemoglobinopathy Gene Therapy: Balancing Efficacy, Toxicity, and the Next Frontier. (PubMed, Blood Adv) - "Busulfan remains the standard, supported by consistent engraftment and clinical efficacy, but is limited by acute and long-term toxicities, including infertility and potential genotoxicity...Reduced-intensity melphalan shows early promise but raises concerns regarding durability, while treosulfan offers a potentially safer profile, though data in the autologous setting are lacking. Antibody-based, nongenotoxic approaches represent a transformative direction but remain investigational. Refining conditioning through comparative trials and long-term follow-up will be critical to fully realizing the curative potential of gene therapy."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Infertility • Sexual Disorders • Sickle Cell Disease

Fludarabine combined with treosulfan or total body irradiation as a conditioning therapy before allogeneic hematopoietic stem cell transplantation in acute lymphoblastic leukemia. A retrospective matched-pair analysis from the ALWP of the EBMT. (PubMed, Bone Marrow Transplant) - "GVHD-free and relapse-free survival was 33.7% and 40.8%, respectively, in FluTreo and FluTBI patients (p = 0.06). In conclusion, there were no significant differences in transplant outcomes between the studied groups."

Journal • Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Treosulfan vs Busulfan for HSCT: A Meta-analysis of Key Outcomes (EAN 2026) - No abstract available

Retrospective data • Bone Marrow Transplantation

A phase II multicenter prospective study to evaluate the safety and efficacy of myeloablative-dose treosulfan plus fludarabine (FT14) conditioning regimen in allogeneic hematopoietic stem cell transplantation for AML patients aged 40-65 in first complete remission. (PubMed, Bone Marrow Transplant) - P2 | "Evidences supporting the use of myeloablative-dose Treosulfan combined with Fludarabine remain largely retrospective, with outdated prospective studies available. Also, FT14 regimen provided an excellent safety with nearly absent NRM, no cases of septic death, and no cases of primary graft failure. Our study supports the use of FT14 as effective myeloablative conditioning regimen for AML patients aged 40-65 y in first complete remission, especially in patients for whom busulfan based conditioning regimens poses excessive toxic risks."

Journal • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Third salvage haematopoietic stem cell transplantation in a child with very early-onset IBD due to interleukin-10 receptor deficiency. (PubMed, BMJ Case Rep) - "Two matched-sibling allogeneic haematopoietic stem cell transplantations using treosulfan-based conditioning engrafted transiently but ultimately failed with autologous recovery and immune cytopenias. A third transplant from the same donor with busulfan/fludarabine/melphalan plus serotherapy and peripheral blood stem cells achieved durable engraftment. Acute skin and gut graft-versus-host disease responded to corticosteroids and etanercept. On long-term follow-up, the patient remained off immunosuppression with stable donor chimerism, normal immunoglobulins, nutritional catch-up (weight), preserved puberty and regular menses though short stature persisted."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Primary Immunodeficiency • Transplantation • IL10