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• W2912159949 abstract "Introduction Hematopoietic stem cell transplantation (HSCT) is a primary treatment for various inherited metabolic diseases (IMDs). Achieving stable and sustained engraftment while minimizing transplant related morbidity and mortality is critical in optimizing outcome for IMDs. Traditional regimens have used myeloablative approaches, primarily Busulfan and Cyclophosphamide (BuCy), which is associated with significant regimen related toxicity (RRT). Alternatively, reduced toxicity regimens, such as Busulfan and Fludarabine (BuFlu), have been proposed to offer similar efficacy with reduced toxicities. Objective To compare outcomes with BuCy and BuFlu based conditioning in patients with IMDs. Methods We retrospectively analyzed University of Minnesota's transplant database for patients with IMDs who underwent HSCT using BuCy (with alemtuzumab) or BuFlu (with ATG) preparative regimen from March, 2008 to September,2017. Overall survival (OS) and incidence of neutrophil and platelet recovery was determined using standard definitions. Complications such as graft failure, sinusoidal obstruction syndrome, hemorrhagic cystitis and respiratory failure were compared. Graft failure includes primary and secondary aplastic graft failure, with and without autologous recovery. Incidence of viral infections post-transplant comparing two regimens were also determined. Results Total of 99 patients underwent HSCT for IMDs during the study period. Sixty-four received BuCy conditioning and 35 received BuFlu. Hurler syndrome (46%) and adrenoleukodystrophy (43%) were most common IMDs and umbilical cord blood was the most common graft source (74%). One-year OS was similar in both groups (81.2% in BuCy vs. 85.5% in BuFlu; p=0.8) with a similar incidence of grade 3-4 acute GVHD(9% vs. 6%; p=0.5) and chronic GVHD(9% vs. 7%; p=0.67). Neutrophil and platelet recovery were similar in both groups with significantly shorter duration of hospital stay noted in BuFlu cohort (median 21 d vs. 34 d, p = 0.002). Cumulative incidence of graft failure was higher with BuFlu group (29% vs 14%, p= 0.08). Significantly higher rates of second HCT was noted following BuFlu cohort (27% vs. 3%, p= 0.001). Incidence of adenoviral infection (14% vs. 0%, p=0.02) and hemorrhagic cystitis (23% vs. 3%, p=0.01) were higher in the BuCy group. T-cell engraftment occurred significantly sooner with BuCy conditioning until 1-year post transplant, donor myeloid engraftment was similar in both groups. Conclusions Reduced toxicity conditioning leads to lower rates of infections and other transplant related complications, but is associated with higher rate of graft failure in patients with IMDs. Alternate immune suppressive agents should be considered to reduce graft failure and minimize toxicities. Alternate donor options, including expanded UCB, should also be considered to improve engraftment in patients with IMDs." @default.
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• W2912159949 date "2019-03-01" @default.
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• W2912159949 title "Reduced Toxicity Conditioning Is Better Tolerated but Has Higher Graft Failure Compared to Myeloablative Conditioning in Children with Inherited Metabolic Disorders" @default.
• W2912159949 doi "https://doi.org/10.1016/j.bbmt.2018.12.116" @default.
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