Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation.

Aims Immunosuppression has become integral to the management of a wide range of childhood illness. Although total numbers of children and young people (CYP) on immunosuppression is unknown, they are thought to be increasing. Multiple paediatric sub-specialities initiate and monitor different immunosuppressive therapies with anecdotal variation in prescribing and monitoring practices. To understand existing variations in care, we undertook a retrospective review, focussing on: Number of CYP on immunosuppression; Drug monitoring and antimicrobial prophylaxis; Numbers of serious infections. Methods CYP attending our hospital on immunosuppressive medication were identified from speciality teams (excluding immunology/oncology patients). Immunosuppressive agents were defined as: Long–term/high–dose steroids Cytotoxic drugs Biologic agents/monoclonal antibodies Data were collected on a representative sample of patients under each speciality: Diagnosis; Current/past immunosuppression; Current/past antimicrobial prophylaxis; Consideration of risk for specific infections; Serious infective episodes. Existing speciality/departmental guidance on prescribing, monitoring and surveillance was collected. Results 416 CYP on immunosuppression identified; data were collected on 77 (18.5%), with cross-speciality representation. 47/77 children are currently prescribed ≥2 agents with 8/77 presently off immunosuppression. 46/77 were not prescribed prophylaxis at any point. In those who were, cotrimoxazole (n=28) was commonest. 54/77 patients had past VZV exposure documented or tested. 7/77 patients attended after chickenpox exposure; 2 required admission for treatment. 10/77 patients were hospitalised for possible bacterial infection; none had proven bacteraemia but 2 developed cryptosporidiosis. All patients had FBC checked with varying frequency (weekly–once only). 14/77 developed lymphopaenia; of these, 8 had subsets checked. There was no clear relationship between speciality and monitoring frequency. Two specialities were able to provide departmental guidance for the management of intercurrent infection. Conclusions There is a large population of CYP on a wide range of immunosuppression. There is inter-speciality variation in the agents prescribed, monitoring schedules, infection risk stratification and antimicrobial prophylaxis. Departmental protocols are uncommon and not readily accessible outside of speciality or hospital, making out-of-hours decisions unnecessarily challenging. This wide variation in practice and lack of evidence-based guidance is unacceptable. Regional immunosuppression guidance may improve the quality of care offered to immunosuppressed children in our region.

Background Mismatched related and unrelated donor stem cell transplantation is considered a high risk transplant associated with high risk of graft loss, graft versus host disease (GvHD) and transplant related mortality (TRM). Alternative graft manipulation strategies have been employed over the last 10 years to reduce these risks, and here we present an analysis of these strategies in primary immunodeficiency (PID). Methods Between 2006–2017, 147 PID patients received 155 mismatched grafts; 30 TCRαβ/CD19 depleted, 43 Cord (72% with no serotherapy), 17 CD34 +selection with T cell add-back and 65 unmanipulated bone marrow or peripheral blood stem cell grafts. Results The estimated 8 year survival of the entire cohort was 79%, TRM was 21.7% and graft failure rate was 6%. Comparable rates of survival were recorded among different graft manipulation strategies. Post-transplant viral reactivation, aGvHD grades II-IV and chronic GvHD complicated 49.6%, 35% and 15% of the transplants, respectively. The use of TCR αβ/CD19 depletion in this study has reduced the occurrence of grade II-IV aGvHD among mismatched transplants: 40% among CD34+/T cell add-back to 11.5% with TCR αβ/CD19 depleted grafts. The same pattern was seen in terms of cGvHD where none of the recipients of TCR αβ/CD19 depleted grafts had cGvHD compared to 38.4% amongst CD34+/T cell add-back. However, one drawback of TCR αβ/CD19 depleted HSCT was the increased incidence of post-transplant viraemia reaching 70% versus 37%–49% among other graft manipulations. T cell immune reconstitution was robust among cord transplants however with a high incidence of aGvHD grade II-IV 56.7%. Stable full donor engraftment was significantly higher at 80% among TCRαβ+/CD19 +depleted and cord transplants versus 40%–60% among the other groups. Conclusions Rapidly accessible cord and haploidentical grafts are suitable alternatives for patients with no HLA matched donor. Cord transplantation without serotherapy and TCRαβ+/CD19 +depleted grafts produced comparable survival rates of around 80% and exhibited higher donor chimerism compared to other strategies of graft manipulation.

Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome