Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders

作者：Burroughs Lauri M^*; Shimamura Akiko; Talano Julie An; Domm Jennifer A; Baker Kelsey K; Delaney Colleen; Frangoul Haydar; Margolis David A; Baker K Scott; Nemecek Eneida R; Geddis Amy E; Sandmaier Brenda M; Deeg H Joachim; Storb Rainer; Woolfrey Ann E

来源：Biology of Blood and Marrow Transplantation, 2017, 23(10): 1669-1677.

DOI：10.1016/j.bbmt.2017.06.002

• Bone marrow failure
• Diamond Blackfan Anemia
• Shwachman-Diamond
• Syndrome
• Reduced-toxicity conditioning in nonmalignant diseases

Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited Marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n =3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n =1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n=12) grafts after conditioning with treosulfan (42 g/m(2)), fludarabine (150 mg/m(2)), +/- thymoglobulin (n =11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.

• 出版日期2017-10