Reduced Toxicity Myeloablative Conditioning Regimen with Busulfan, Fludarabine and Alemtuzumab for Children with Non-Malignant Disorders, Myelodysplastic Syndrome (MDS) and Myeloid Malignancies
Year: 2009
Type: article
Abstract: Major problems with Busulfan/Cyclophosphamide (Bu/Cy) conditioning are acute toxicities and graft failure. In 2000, we replaced Bu/Cy conditioning with targeted i.v. Busulfan/Fludarabine/rabbit ATG (Bu/Flu/rATG) which effectively reduced acute toxicities; however, graft failure rate remained high (21%). In 2004, we introduced targeted i.v. Busulfan/Fludarabine and Alemtuzumab (Bu/Flu/Campath) to reduce graft failure rate. We describe and compare the outcomes of the first 21 Bu/Flu/Campath study patients (median age 8, range 1–16 years) with those of previously published 19 By/Flu/rATG study patients. Diagnoses included MDS or myeloid malignancy (N = 5), hemoglobinopathy (N = 3), non-SCID primary immunodeficiency (N = 6), aplastic anemia (N = 2), autoimmune disorders (N = 2), and metabolic disorders (N = 3). The donors included ≥8/8 HLA-matched (N = 6) and one antigen mismatched (N = 4) unrelated volunteers, and fully matched related donors (N = 11). Stem cell sources were peripheral blood (N = 9), bone marrow (N = 10) or combined sources (N = 2). 19/20 evaluable patients engrafted. One patient with Hurler's disease developed graft rejection 40 days post transplant but was rescued with a 2nd transplant. The median follow-up of living patients is 21 months (range 4.3–51 months). Estimated 2-year post-transplant overall and event-free survival rates were 83 ± 9% and 71 ± 11%, respectively, which is similar to survival in the Bu/Flu/rATG study (89 ± 7% and 74 ± 10%). Three patients died (at 1, 5, and 12 months post transplant) due to intracranial hemorrhage in 1 patient with Evans syndrome, Aspergillus infection and GVHD in 1 patient with adrenal leukodystrophy (ALD), and disease progression and GVHD in 1 patient with ALD. One patient with MDS relapsed 1 year following the transplant, but is alive following the 2nd successful transplant. CMV reactivated in 47% (7/15) patients who were at risk for reactivation and was successfully treated in all. Only 1 patient developed mild VOD (maximum total bilirubin 3.4 mg/dl). The incidence of acute and chronic GVHD was 15% each, respectively. At last follow up 85% of patients remain mixed chimeras. Bu/Flu/Campath conditioning was well tolerated and resulted in durable mixed chimerism in the majority of patients. Compared with Bu/Flu/rATG, Bu/Flu/Campath conditioning resulted in significantly reduced graft rejection rate (2-tailed Fisher's exact p = 0.03) in mismatched MUD transplants, but it did not improve overall survival or event free-survival.
Institution: University of California, San Francisco
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2031212609