TY - JOUR
T1 - Hematopoietic Cell Transplantation for Mucopolysaccharidosis Patients Is Safe and Effective: Results after Implementation of International Guidelines
AU - Aldenhoven, Mieke
AU - Jones, Simon A.
AU - Bonney, Denise
AU - Borrill, Roisin E.
AU - Coussons, Mary
AU - Mercer, Jean
AU - Bierings, Marc B.
AU - Versluys, Birgitta
AU - van Hasselt, Peter M.
AU - Wijburg, Frits A.
AU - van der Ploeg, Ans T.
AU - Wynn, Robert F.
AU - Boelens, Jaap Jan
PY - 2015
Y1 - 2015
N2 - Allogeneic hematopoietic cell transplantation, (HCT) is the only treatment able to prevent progressive neurodegenerative disease in a selected group of mucopolysaccharidosis (MPS) disorders. However, its use was historically limited by the high risk of graft failure and transplantation-related morbidity and mortality. Therefore; since 2005 new international HCT guidelines for MPS disorders were proposed. The survival and graft outcomes of MPS patients receiving HCT according to these guidelines in 2 European centers of expertise were,evaluated. Two consecutive conditioning regimens were used, busulfan/cyclophosphamide or, fludarabine/busulfan-based, both with exposure-targeted i.v. busulfan. A noncarrier matched sibling donor (MSD), matched unrelated cord blood (UCB), or matched unrelated donor (MUD) were considered to be preferred donors. If not available, a mismatched UCB donor was used. Participants were 62 MPS patients (56 MPS type I Hurler, 2 MPS type II, 2 MPS type III, and 2 MPS type VI) receiving HCT at median age 13.5 months (range, 3 to 44). Forty-one patients received a UCB donor, 17 MSD, and 4 MUD. High overall survival (95.2%) and event-free survival (90.3%) were achieved with only low toxicity: 13.3% acute graft-versus-host disease aGVHD) grades II to IV and 14.8% chronic GVHD (1.9% extensive). A mismatched donor predicted for lower event-free survival (P = .04). A higher age at HCT was a predictor for both aGVHD (P = .001) and chronic GVHD (P = .01). The use of a mismatched donor was a predictor for aGVHD (P = .01). Higher rates of full-donor chimerism were achieved in successfully transplanted UCB recipients compared with MSD/MUD (P = .002). If complying with the international HCT guidelines, HCT in MPS patients results in high safety and efficacy. This allows extension of HCT to more attenuated MPS types. Because a younger age at HCT is associated with reduction of HCT-related toxicity, newborn screening may further increase safety. (C) 2015 American Society for Blood and Marrow Transplantation
AB - Allogeneic hematopoietic cell transplantation, (HCT) is the only treatment able to prevent progressive neurodegenerative disease in a selected group of mucopolysaccharidosis (MPS) disorders. However, its use was historically limited by the high risk of graft failure and transplantation-related morbidity and mortality. Therefore; since 2005 new international HCT guidelines for MPS disorders were proposed. The survival and graft outcomes of MPS patients receiving HCT according to these guidelines in 2 European centers of expertise were,evaluated. Two consecutive conditioning regimens were used, busulfan/cyclophosphamide or, fludarabine/busulfan-based, both with exposure-targeted i.v. busulfan. A noncarrier matched sibling donor (MSD), matched unrelated cord blood (UCB), or matched unrelated donor (MUD) were considered to be preferred donors. If not available, a mismatched UCB donor was used. Participants were 62 MPS patients (56 MPS type I Hurler, 2 MPS type II, 2 MPS type III, and 2 MPS type VI) receiving HCT at median age 13.5 months (range, 3 to 44). Forty-one patients received a UCB donor, 17 MSD, and 4 MUD. High overall survival (95.2%) and event-free survival (90.3%) were achieved with only low toxicity: 13.3% acute graft-versus-host disease aGVHD) grades II to IV and 14.8% chronic GVHD (1.9% extensive). A mismatched donor predicted for lower event-free survival (P = .04). A higher age at HCT was a predictor for both aGVHD (P = .001) and chronic GVHD (P = .01). The use of a mismatched donor was a predictor for aGVHD (P = .01). Higher rates of full-donor chimerism were achieved in successfully transplanted UCB recipients compared with MSD/MUD (P = .002). If complying with the international HCT guidelines, HCT in MPS patients results in high safety and efficacy. This allows extension of HCT to more attenuated MPS types. Because a younger age at HCT is associated with reduction of HCT-related toxicity, newborn screening may further increase safety. (C) 2015 American Society for Blood and Marrow Transplantation
U2 - https://doi.org/10.1016/j.bbmt.2015.02.011
DO - https://doi.org/10.1016/j.bbmt.2015.02.011
M3 - Article
C2 - 25708213
SN - 1083-8791
VL - 21
SP - 1106
EP - 1109
JO - Biology of blood and marrow transplantation
JF - Biology of blood and marrow transplantation
IS - 6
ER -