Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications.

Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more often HLA-mismatched compared to other unrelated donor transplants. The ability to transplant in such a setting, indeed without high rates of chronic Graft versus Host Disease (GVHD), constitutes an advantage compared to other unrelated donor cell sources and there are other advantages specifically associated with cord blood as a donor cell source. These advantages must be weighed against its disadvantage, and we have utilised cord blood preferentially as a donor cell source in certain clinical situations in paediatric medicine. In non-malignant diseases, outcomes in metabolic disease are critically dependent on age at transplant and the enzyme delivered by that transplant, and in cord blood transplantation then the time to transplant can be minimised and the engrafted recipients have higher chimerism that delivers higher enzyme levels. In malignant diseases, studies have described reduced relapse rate and better GVHD-free survival, and so we have prioritised cord as a donor cell source where the risk of relapse is highest, and the effects of higher transplant related mortality is most clearly offset by the reduced relapse rates.

A decade of excellent transplant survival in children with inherited metabolic diseases: A report from a single metabolic transplant centre in Europe.

Hematopoietic cell transplantation (HCT) confers a long-term disease-modifying therapy for transplant-permissive inherited metabolic diseases (IMDs). We examined the overall survival (OS) and engrafted survival (ES) of children with IMDs, who received first HCT at Royal Manchester Children's hospital from 1985 to 2016. A total of 137 children with IMDs were included in this analysis (historical cohort [1985-2006], n＝65; current cohort [2007-2016], n＝72). Primary diagnoses included mucopolysaccharidoses (81%), X-linked adrenoleukodystrophy (6%), metachromatic leukodystrophy (4%), mannosidosis (3%), Wolman disease (2%), and other conditions (4%). The five-year OS has increased from 65% (95% confidence interval [CI], 52%-76%) in the historical cohort to 91% (95% CI, 81%-96%) in the current cohort (P<0.001). Moreover, the five-year ES, which was 64% (95 CI%, 56%-72%) for the entire cohort, has doubled from 41% (95% CI, 29%-53%) in the historical cohort to 85% (95% CI, 75%-92%) in the current cohort (P<0.001). The proportion of patients with graft failure has decreased from 37% in the historical cohort to 8% in the current cohort (P<0.001). In patients who received a second transplant, 13 out of 20 patients (65%) in the historical cohort and all four in the current cohort were alive and engrafted. Of 82 survivors followed-up at Manchester, 80% and 20% had full and mixed chimerism, respectively. Although this study was restricted to a single center, our findings show that HCT is an increasingly safe procedure and provides long-lasting endogenous enzyme replacement therapy for children with IMDs in the modern era of HCT.

Incarcerated fibroid uterus: the role of conservative management.

BACKGROUND: Uterine incarceration occurs when the gravid uterus remains trapped within the sacral hollow and cannot ascend out of the pelvis as it enlarges. Predisposing factors include uterine fibroids. Optimal management of uterine incarceration involves manual reduction of the uterus because of the significant maternal and fetal risks associated with persistent incarceration. CASE: A nulliparous woman with known uterine incarceration secondary to a large anterior uterine fibroid was managed conservatively throughout her pregnancy after attempts at manual reduction were unsuccessful. CONCLUSION: Conservative management of the incarcerated uterus is a reasonable option if attempts at manual reduction are unsuccessful. Magnetic resonance imaging can be helpful in delineating anatomy and planning for delivery.

Contexte : On parle d'incarcération utérine lorsque l'utérus d'une femme enceinte demeure coincé dans le creux du sacrum et ne peut cheminer hors du bassin au fur et à mesure de son expansion. La présence de fibromes utérins fait partie des facteurs prédisposants. La prise en charge optimale de l'incarcération utérine met en jeu la réduction manuelle de l'utérus, et ce, en raison des risques maternels et fœtaux considérables qui sont associés à la persistance de l'incarcération. Cas : Une nullipare, chez qui la présence d'une incarcération utérine attribuable à un gros fibrome utérin antérieur était connue, a fait l'objet d'une prise en charge conservatrice tout au long de sa grossesse, après l'échec de tentatives de réduction manuelle. Conclusion : La prise en charge conservatrice de l'incarcération utérine constitue une option raisonnable à la suite de l'échec de tentatives de réduction manuelle. L'imagerie par résonance magnétique peut s'avérer utile pour situer l'anatomie et planifier l'accouchement.