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Developing quality assurance for pediatric autologous stem cell transplants in England: results of a 3-year national audit of activity and engraftment by treatment centre

Bone Marrow Transplantation volume 52, pages 922–925 (2017)Cite this article

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High-dose chemotherapy (HDC) followed by reinfusion of cryopreserved autologous PBSC or, less frequently, bone marrow-derived stem cells (BMDSC) is used in the treatment of several pediatric malignancies. In September 2013, a series of six patients undergoing HDC with autologous PBSC rescue at Great Ormond Street Hospital (GOSH), London, who experienced significantly delayed count recovery, was identified. Two additional patients who received cryopreserved allogeneic BMDSC and experienced delayed marrow reconstitution were also identified. This led to the declaration of a Serious Incident and an extensive investigation into the transplant processes in place at GOSH.1, 2 Ultimately a problem with cryopreservation was identified and a revised process established. Retrospective review showed a significant number of patients with delayed neutrophil recovery over many years. However, without a robust system for the data collection, real-time analysis and benchmarking against other centres these issues with delayed engraftment had not been appreciated. Four of these patients with delayed engraftment died and the cases were referred to HM Coroner, who issued a Prevention of Future Deaths Report requiring NHS England to establish improved governance procedures around pediatric autografts. A National Paediatric Autograft Panel (NPAP) has been established and, under its auspices, a national audit of paediatric autograft activity and the engraftment data was undertaken with the aims of determining current national practice and ensuring that any other centres affected by problems with cryopreservation or other issues were identified; prompt engraftment being the ultimate quality measure for successful cell processing.3

The data were collected retrospectively for the 3-year period 1 September 2012 to 31 August 2015 (based on the date of stem cell return) from each pediatric oncology principal treatment centre (PTC) in England. There was no specific upper limit on patient age. All procedures involving administration of autologous PBSC/BMDSC following HDC were included (regardless of whether such treatment was myeloablative). Each PBSC/BMDSC reinfusion was recorded as a separate procedure. Neutrophil recovery was defined as the first of three consecutive days of neutrophil count >0.5 × 109/L regardless of G-CSF use, and platelet recovery as the first of three consecutive days of platelet count >20 × 109/L with no platelet transfusion in the preceding 7 days. The data were analysed using Prism (Graphpad Software Inc, La Jolla, CA, USA) to calculate median recovery times and 95% percentiles. Median recovery times at different centres were compared to those of the remaining centres using Mann–Whitney test. Bonferroni correction for multiple comparisons was used to determine statistical significance of calculated P values.

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Acknowledgements

The national audit was conducted under the auspices of the NHS England National Paediatric Autograft Panel: Martin English, Simon Hack, Darren Hargrave, Vicky Holden, Rachel Hollis, DAM, James Nicholson, Caroline Osborne, AP, Roderick Skinner, MW, KW and Robert Wynn. We are grateful for the assistance of the clinical leads at each centre in supplying the data: Martin Elliott (Leeds Teaching Hospitals); Martin English (Birmingham Children’s Hospital); Richard Grundy (Queen’s Medical Centre, Nottingham); James Hayden (Alder Hey Children’s NHS Foundation Trust, Liverpool); Rachael Hough (University College London Hospital); Steve Lowis (Bristol Royal Hospital for Children); DAM (Great Ormond Street Hospital, London); Matthew Murray (Addenbrooke’s University Hospital, Cambridge); Helen Oram (University Hospital Southampton); Anthony Penn (Royal Manchester Children’s Hospital); Roderick Skinner (Royal Victoria Infirmary, Newcastle upon Tyne); Sucheta Vaidya (Royal Marsden Hospital, Sutton); KW (Oxford University Hospitals); Daniel Yeomanson (Sheffield Children’s Hospital).

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Authors and Affiliations

  1. Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    D A Morgenstern

  2. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada

    D A Morgenstern

  3. Women and Children National Programme of Care, NHS England, Skipton House, London, UK

    P Gray & A Prudhoe

  4. Wolfson Cellular Therapy Unit, University College London Hospitals, London, UK

    M Watts

  5. Paediatric Oncology, The Children’s Hospital, The John Radcliffe, Oxford, UK

    K Wheeler

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  1. D A Morgenstern
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  2. P Gray
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  4. M Watts
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Correspondence to D A Morgenstern.

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Morgenstern, D., Gray, P., Prudhoe, A. et al. Developing quality assurance for pediatric autologous stem cell transplants in England: results of a 3-year national audit of activity and engraftment by treatment centre. Bone Marrow Transplant 52, 922–925 (2017). https://doi.org/10.1038/bmt.2017.32

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