An experimental, open-label, phase 2 trial set to evaluate whether treosulfan, fludarabine, and rabbit antithymocyte globulin treatment given prior to a blood or bone marrow transplant may reduce postoperative complications in people with bone marrow failure diseases, including myelodysplastic syndromes (MDS), is still recruiting.

According to the latest update that specified the treatment plan, the study participants will be administered treosulfan intravenously over 120 minutes on days −6 to −4, intravenous fludarabine phosphate over 60 minutes on days −6 to −2, and intravenous lapine T-lymphocyte immune globulin over 4 to 6 hours on days −4 to −2. The day of the bone marrow or peripheral blood stem cell transplantation is marked as day 0.

Study participants will also receive the graft-versus-host-disease (GVHD) prophylaxis which consists of tacrolimus, given orally as well as intravenously at day −2 and a taper beginning on day 180, and administered intravenously on days 1, 3, 6, and 11. Patients will be followed up at 1-year post-transplantation.

Approximately 40 patients aged 1 to 49 years will take part in this trial. The study inclusion criteria provide detailed diagnostic criteria and indications for hematopoietic cell transplantation for each of the following conditions: Shwachman-Diamond syndrome, Diamond Blackfan anemia, congenital sideroblastic anemia, GATA2 mutation with associated marrow failure, SAMD9 or SAMD9L disorders, congenital amegakaryocytic thrombocytopenia, and paroxysmal nocturnal hemoglobinuria. The latest update also lists detailed instructions and recommendations regarding different donor types.  

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The primary outcome measure has remained the GVHD-free event-free survival. The secondary outcome measures include overall survival, event-free survival, neutrophil and platelet recovery, donor chimerism, primary and secondary graft failure or rejection, 2 to 4 and grade 3 to 4 GVHD, chronic GVHD, incidence of grade 3 to 5 toxicities, grade 2 to 3 systemic infections, Epstein Barr virus reactivation requiring therapy and its associated lymphoproliferative disorder, and cytomegalovirus reactivation requiring therapy.

Although initially set in the states of Georgia, Michigan, North Carolina, and Virginia, the study will also be conducted across several United States locations in California, Colorado, Maryland, Massachusetts, Minnesota, Missouri, New York, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Utah, Washington, and Wisconsin. According to the latest update, the study will not be conducted in the state of Virginia.

The study start date was supposed to be August 2021, however, it actually began on April 19, 2022. The primary completion date is estimated to be December 2025, while the estimated study completion date is set as December 2026.

The trial, sponsored by Fred Hutchinson Cancer Center, will be conducted in collaboration with the Blood and Marrow Transplant Clinical Trials Network, the National Cancer Institute, the National Marrow Donor Program, and the National Heart, Lung, and Blood Institute.


Treosulfan-based conditioning regimen before a blood or bone marrow transplant for the treatment of bone marrow failure diseases (BMT CTN 1904). Published July 16, 2021. Last updated July 12, 2023. Accessed July 12, 2023.