Browsing by Author "Escolar, Maria"

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    Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry.
    (Analytical chemistry, 2020-05) Hong, Xinying; Kumar, Arun Babu; Daiker, Jessica; Yi, Fan; Sadilek, Martin; De Mattia, Fabiola; Fumagalli, Francesca; Calbi, Valeria; Damiano, Roberta; Della Bona, Maria; la Marca, Giancarlo; Vanderver, Adeline L; Waldman, Amy T; Adang, Laura; Sherbini, Omar; Woidill, Sarah; Suhr, Teryn; Kurtzberg, Joanne; Beltran-Quintero, Maria L; Escolar, Maria; Aiuti, Alessandro; Finglas, Alan; Olsen, Amber; Gelb, Michael H
    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spots (DBS) using deuterated natural sulfatide substrate. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) displayed a clear deficit in the enzymatic activity and could be completely distinguished from normal controls. The leukocyte assay reported here will be important for diagnosing MLD and MSD patients and for monitoring the efficacy of therapeutic treatments. ARSA activity was measured in DBS for the first time without an antibody. This new ARSA DBS assay can serve as a second-tier test following the sulfatide measurement in DBS for newborn screening of MLD. This leads to an elimination of most of the false positives identified by the sulfatide assay.
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    Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning.
    (Blood, 2013-05) Boelens, Jaap Jan; Aldenhoven, Mieke; Purtill, Duncan; Ruggeri, Annalisa; Defor, Todd; Wynn, Robert; Wraith, Ed; Cavazzana-Calvo, Marina; Rovelli, Attilio; Fischer, Alain; Tolar, Jakub; Prasad, Vinod K; Escolar, Maria; Gluckman, Eliane; O'Meara, Anne; Orchard, Paul J; Veys, Paul; Eapen, Mary; Kurtzberg, Joanne; Rocha, Vanderson; Eurocord; Inborn Errors Working Party of European Blood and Marrow Transplant group; Duke University Blood and Marrow Transplantation Program; Centre for International Blood and Marrow Research
    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 = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .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.
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    Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with and without Hematopoietic Stem Cell Transplantation.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2019-03) Raymond, Gerald V; Aubourg, Patrick; Paker, Asif; Escolar, Maria; Fischer, Alain; Blanche, Stephane; Baruchel, André; Dalle, Jean-Hugues; Michel, Gérard; Prasad, Vinod; Miller, Weston; Paadre, Susan; Balser, John; Kurtzberg, Joanne; Nascene, David R; Orchard, Paul J; Lund, Troy
    Cerebral adrenoleukodystrophy (CALD) is a rapidly progressing, often fatal neurodegenerative disease caused by mutations in the ABCD1 gene, resulting in deficiency of ALD protein. Clinical benefit has been reported following allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a large multicenter retrospective chart review to characterize the natural history of CALD, to describe outcomes after HSCT, and to identify predictors of treatment outcomes. Major functional disabilities (MFDs) were identified as having the most significant impact on patients' abilities to function independently and were used to assess HSCT outcome. Neurologic function score (NFS) and Loes magnetic resonance imaging score were assessed. Data were collected on 72 patients with CALD who did not undergo HSCT (untreated cohort) and on 65 patients who underwent transplantation (HSCT cohort) at 5 clinical sites. Kaplan-Meier (KM) estimates of 5-year overall survival (OS) from the time of CALD diagnosis were 55% (95% confidence interval [CI], 42.2% to 65.7%) for the untreated cohort and 78% (95% CI, 64% to 86.6%) for the HSCT cohort overall (P = .01). KM estimates of 2-year MFD-free survival for patients with gadolinium-enhanced lesions (GdE+) were 29% (95% CI, 11.7% to 48.2%) for untreated patients (n = 21). For patients who underwent HSCT with GdE+ at baseline, with an NFS ≤1 and Loes score of 0.5 to ≤9 (n = 27), the 2-year MFD-free survival was 84% (95% CI, 62.3% to 93.6%). Mortality rates post-HSCT were 8% (5 of 65) at 100days and 18% (12 of 65) at 1 year, with disease progression (44%; 7 of 16) and infection (31%; 5 of 16) listed as the most common causes of death. Adverse events post-HSCT included infection (29%; 19 of 65), acute grade II-IV graft-versus-host disease (GVHD) (31%; 18 of 58), and chronic GVHD (7%; 4 of 58). Eighteen percent of the patients (12 of 65) experienced engraftment failure after their first HSCT. Positive predictors of OS in the HSCT cohort may include donor-recipient HLA matching and lack of GVHD, and early disease treatment was predictive of MFD-free survival. GdE+ status is a strong predictor of disease progression in untreated patients.‎ This study confirms HSCT as an effective treatment for CALD when performed early. We propose survival without MFDs as a relevant treatment goal, rather than solely assessing OS as an indicator of treatment success.
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    Umbilical cord blood transplantation to treat Pelizaeus-Merzbacher Disease in 2 young boys.
    (Pediatrics, 2014-11) Wishnew, Jessica; Page, Kristin; Wood, Susan; Galvin, Leo; Provenzale, James; Escolar, Maria; Gustafson, Kathryn; Kurtzberg, Joanne
    Pelizaeus-Merzbacher Disease (PMD) is a rare X-linked recessive leukodystrophy caused by mutations in the proteolipid protein 1 gene on the Xq22 chromosome. PMD is a dysmyelinating disorder characterized by variable clinical presentation and course. Symptoms range from mild motor deficits to progressive spasticity and neurologic decline resulting in death at an early age. There is no definitive curative treatment. This report presents the clinical course of 2 young boys with PMD who are the first known patients to receive umbilical cord blood transplantation as a therapeutic intervention to stabilize disease progression. Pretransplantation evaluation revealed that both patients had significant motor deficits as well as delayed cognitive function as compared with age-matched peers. Brain imaging revealed varying degrees of hypomyelination. Both patients received myeloablative chemotherapy followed by an unrelated donor umbilical cord blood infusion, which they tolerated well with no major transplantation-related complications. At 7-years and 1-year posttransplantation, respectively, both boys are making slow neurocognitive improvements and show no evidence of functional decline. Imaging results show stable or improving myelination. Although the results of unrelated donor umbilical cord blood transplantation in these 2 boys with PMD are encouraging, longer-term follow-up will be necessary to assess the effect of this treatment on the variable natural disease course.