Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning

Abstract

• In HS, patients' early referral for HCT, with the best available HLA-matched donor offers the best event-free survival.• In HS, patients' HCT with a well-matched unrelated cord blood unit is particularly attractive because the unit is readily available.We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P 5 .031) and HLA-mismatched UD (41%; P 5 .007). Full-donor chimerism (P 5 .039) and normal enzyme levels (P 5 .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS. (Blood. 2013;121(19):3981-3987)

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

“…Multiple reasons probably contributed to their deaths. In common, both deceased patients received grafts from unrelated donors, an already-known factor associated with increased risk of mortality 26,27 . Moreover, the CALD-7 patient started with symptoms in adulthood, another factor associated with higher HSCT morbidity and mortality risks 27 .…”

“…In common, both deceased patients received grafts from unrelated donors, an already-known factor associated with increased risk of mortality 26,27 . Moreover, the CALD-7 patient started with symptoms in adulthood, another factor associated with higher HSCT morbidity and mortality risks 27 . Although mortality rates after HSCT in CALD of less than 5% have been reported 7 , none of the studies on HSCT outcomes published so far included adult forms 15 .…”

Newborn Screening for Hunter Disease: A Small-Scale Feasibility Study

“…Early HSCT of patients with Hunter syndrome has not been reported to date. However, for other lysosomal storage disorders the benefits of early treatment have been shown, including Hurler disease (Boelens et al 2013). Early intervention requires identification of patients at a very early age, before clinical features have become evident, i.e., by newborn screening (NBS) (Marsden and Levy 2010;Zhou et al 2011).…”

Umbilical cord blood donation: public or private?

“…Superior outcomes were demonstrated in Hurler syndrome, Krabbe disease, Metachromatic leukodystrophy and a series of rare inborn errors of metabolism. [18][19][20][21][22] Related UCBT is curative in children with hemoglobinopathies. 23 The use of UCBT in these patients has been more challenging with a high incidence of graft failure and transplant-related mortality.…”