Browsing by Author "Allewelt, Heather"

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    Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies.
    (Blood Adv, 2018-01-09) van den Broek, Brigitte TA; Page, Kristin; Paviglianiti, Annalisa; Hol, Janna; Allewelt, Heather; Volt, Fernanda; Michel, Gerard; Diaz, Miguel Angel; Bordon, Victoria; O'Brien, Tracey; Shaw, Peter J; Kenzey, Chantal; Al-Seraihy, Amal; van Hasselt, Peter M; Gennery, Andrew R; Gluckman, Eliane; Rocha, Vanderson; Ruggeri, Annalisa; Kurtzberg, Joanne; Boelens, Jaap Jan
    Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%;P= .006), well-matched (≤1 HLA mismatch) CB units (71% vs 54%;P= .009), and performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%, respectively;P= .003). For patients with PS≤60 (n = 20) or 60 to 80 (n = 24) pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS >80 pre-CBT, 50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes.
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    Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2016-09) Allewelt, Heather; El-Khorazaty, Jill; Mendizabal, Adam; Taskindoust, Mahsa; Martin, Paul L; Prasad, Vinod; Page, Kristin; Sanders, Jean; Kurtzberg, Joanne
    Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.
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    Long-Term Functional Outcomes following Hematopoietic Stem Cell Transplant for Early Infantile Krabbe Disease.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2018-06-19) Allewelt, Heather; Taskindoust, Mahsa; Troy, Jesse; Page, Kristin; Wood, Susan; Parikh, Suhag; Prasad, Vinod K; Kurtzberg, Joanne
    Allogeneic hematopoietic stem cell transplantation (HSCT) can retard the progression of early infantile Krabbe disease (EIKD). Superior outcomes are achieved if HSCT is performed prior to the onset of symptoms, however little information is available about the long-term outcomes in surviving patients. We now describe functional outcomes in pre-symptomatic infants who underwent HSCT for EIKD at ≤2 months of life. Records of the 19 patients who underwent HSCT for EIKD at ≤2 months of age from 1996-2010 were reviewed. Long-term functional outcomes were compared between those transplanted at <30 days and ≥30 days of life. Median age at transplant was 27 days (range 19-61). Median follow-up of the cohort was 12.6 years. Overall survival at 5 and 10 years post-transplant was 84.2% (95% CI:58.7-94.6%) and 78.6% (95% CI:52.5-91.4%), respectively. More favorable outcomes were seen in patients who underwent HSCT at <30 days of age, particularly in domains of mobility (p=0.01), communication (p=0.02), and feeding (p=0.008). Improved functional outcomes were observed when HSCT was performed in the first month of life, defining a critical period for intervention. These results support the implementation of newborn screening to enable rapid diagnosis and early treatment of infants with EIKD.
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    Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study.
    (Blood, 2015-03) Aldenhoven, Mieke; Wynn, Robert F; Orchard, Paul J; O'Meara, Anne; Veys, Paul; Fischer, Alain; Valayannopoulos, Vassili; Neven, Benedicte; Rovelli, Attilio; Prasad, Vinod K; Tolar, Jakub; Allewelt, Heather; Jones, Simon A; Parini, Rossella; Renard, Marleen; Bordon, Victoria; Wulffraat, Nico M; de Koning, Tom J; Shapiro, Elsa G; Kurtzberg, Joanne; Boelens, Jaap Jan
    Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients with MPS-IH after HCT are lacking. The goal of this international study was to identify predictors of the long-term outcome of patients with MPS-IH after successful HCT. Two hundred seventeen patients with MPS-IH successfully engrafted with a median follow-up age of 9.2 years were included in this retrospective analysis. Primary endpoints were neurodevelopmental outcomes and growth. Secondary endpoints included neurologic, orthopedic, cardiac, respiratory, ophthalmologic, audiologic, and endocrinologic outcomes. Considerable residual disease burden was observed in the majority of the transplanted patients with MPS-IH, with high variability between patients. Preservation of cognitive function at HCT and a younger age at transplantation were major predictors for superior cognitive development posttransplant. A normal α-l-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-term prognosis of patients with MPS-IH receiving HCT can be improved by reducing the age at HCT through earlier diagnosis, as well as using exclusively noncarrier donors and achieving complete donor chimerism.
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    Survey of quality of life, phenotypic expression, and response to treatment in Krabbe leukodystrophy.
    (JIMD reports, 2019-05) Langan, Thomas J; Barczykowski, Amy; Jalal, Kabir; Sherwood, Laura; Allewelt, Heather; Kurtzberg, Joanne; Carter, Randy L

    Objectives

    To develop a quality of life (QOL) survey for Krabbe disease (KD), and to thereby improve understanding of its phenotypic expression and response to treatment.

    Methods

    The survey, the Leukodystrophy Quality of Life Assessment (LQLA) and the Vineland Adaptive Behavior Scales were co-administered to 33 patients or their caretakers. These included the phenotypes of early infantile KD (EIKD; 0-6 months old at onset), late infantile cases (LIKD; 7-12 months old at onset), and cases that emerged after 12 months old, late onset (LOKD). The sample included cases with and without stem cell transplantation (SCT). Reliability and concurrent validity were assessed for overall and subscale scores. Analysis of variance tested differences in QOL between phenotypes and transplant groups (none, pre-, post-symptom).

    Results

    Good concurrent validity with the Vineland was shown for total, communication, daily activity, social, and motor scales and good reliability was observed. LOKD cases had better communication skills than either EIKD or LIKD and better overall QOL than EIKD. Analyses of individual items showed that communication items, mostly, contributed significantly to phenotype differences. Presymptomatic SCT significantly improved QOL compared to postsymptomatic SCT or no treatment. Presymptomatically treated patients had near-normal total scores.

    Conclusions

    The LQLA is valid and reliable. Despite small sample size, phenotypic demarcation was determined to be due mainly to differences in communication skills. There was a relative enhancement of QOL in LOKD patients, and in those who had presymptomatic SCT. These results apply to the current controversy about recommendations for newborn screening for this condition.