UK Haemoglobin Disorders Peer Review: A Quality Standards-based review programme for sickle cell disease and thalassaemia.

We evaluated the impact of peer reviews in driving improvement in healthcare quality for people with haemoglobinopathy in the United Kingdom. We analysed compliance to four Quality Standards (QS)-based peer reviews from 2010 to 2020 to evaluate its impact in driving healthcare quality. Seventeen paediatric and 29 adult haemoglobinopathy centres were reviewed in 2010/11 and 2012/13 respectively; 33 paediatric and 33 adult centres were reviewed in 2014/16, and 32 paediatric and 32 adult centres were reviewed in 2018/2020. Compliance with QS and participant feedback were analysed to assess the impact of peer review programmes to drive improvement in quality of care. We noted that haemoglobinopathy centres significantly improved their compliance to QS between the first two review programmes, but not in the final review programme. In comparison to other disease-group reviews, the haemoglobinopathy departments were less able to address critical peer review recommendations in their own institutions. The peer review programme was unable to drive sustained improvement in healthcare quality, underscoring the need for sustained development and support for haemoglobinopathy services in the National Health Service. Further work is needed to understand why disparities exist among peer review-driven improvement initiatives within different disease groups.

Quality of life Evaluation in patients receiving Steroids (the QuESt tool): initial development in children and young people with acute lymphoblastic leukaemia.

BACKGROUND: The powerful cytotoxic and immunomodulatory effects of corticosteroids are an important element of the success that has been achieved in the treatment of acute lymphoblastic leukaemia (ALL). In addition to physical side effects, corticosteroids can adversely influence behaviour, cognitive function and mood leading to significantly impaired quality of life (QoL). A number of tools exist for assessing QoL, but none of these specifically examines changes attributable to steroids. METHODS: Children and young adults aged 8-24 years and parents of children receiving maintenance therapy for ALL from four UK centres were invited to participate. The study comprised three stages carried out over 2 years: (1) focus groups and interviews where participants were asked to describe their experiences of dexamethasone; (2) analysis of questionnaires sent to healthcare professionals and patients to evaluate the importance and relevance of the questions; and (3) cognitive interviewing. RESULTS: Interpretative phenomenological analysis of focus group and interview transcripts identified that dexamethasone adversely influenced behaviour, appetite, body image, mood and family relationships. 157 electronic survey responses were analysed leading to further item development. Cognitive interviewing confirmed face validity and internal consistency. QuESt comprises 28 questions within four domains and has three age-specific versions. CONCLUSIONS: QuESt is the first treatment-specific QoL measure for children and young adults receiving corticosteroids. It can be completed in 10-15 min by children aged ≥8 years. Further validity and reliability testing will be undertaken. Although the initial application is for ALL, QuESt may also be a valuable tool for understanding the impact of corticosteroids in other paediatric conditions.

Transient abnormal myelopoiesis associated with Down syndrome presenting as severe hydrops fetalis: a case report.

We present a case of transient abnormal myelopoiesis (TAM) presenting as non-immune fetal hydrops (NIHF). Hydrops fetalis (HF) is a condition associated with very high perinatal mortality, especially when no treatable cause, such as fetal anaemia, exists. In fetuses prior to 24 weeks with NIHF, a chromosomal anomaly is a common association. TAM is a leukaemic condition, almost entirely limited to children with Down syndrome. The presentation of TAM prenatally is unusual but cases may present ultrasonographically with NIHF and associated fetal hepatosplenomegaly. We report a case presenting in this manner with NIHF detected at 29 weeks' gestation and discuss the subsequent diagnosis and management of in utero TAM.

Donor lymphocyte infusions for post-transplant relapse of refractory anemia with excess blasts and monosomy 7.

An 8-year-old male relapsed with refractory anemia with excess blasts (RAEB) and monosomy 7 and mixed chimerism (MC) 21 months after HLA-matched unrelated donor bone marrow transplant (BMT). He received three donor lymphocyte infusions (DLI) using an escalating dose schedule. He developed grade II acute graft-versus-host disease (GVHD) 9 days after the third DLI, but continued to deteriorate for 2 months with decreasing marrow cellularity but persisting blasts, MC, and monosomy 7, before exhibiting a delayed but complete response which has persisted for 5 years. This case suggests that DLI and graft-versus-myelodysplasia (GVMDS) may be beneficial in post-transplant relapse of pediatric myelodysplasia.

Failure of rituximab to induce immune tolerance in a boy with severe haemophilia A and an alloimmune factor VIII antibody: a case report and review of the literature.

We report the use of rituximab (MabThera); Roche Grenzach-Wyhlen, Germany) in a 6-year-old boy with severe haemophilia A and a high titre alloimmune factor VIII (FVIII) antibody, which had failed to respond to standard immune tolerance therapy. Rituximab was administered in 4 weekly doses with concurrent high-dose i.v. immunoglobulin (Flebogamma); Grifols, Barcelona, Spain) followed by daily high-dose recombinant FVIII concentrate (Recombinate); Baxter, CA, USA). Despite a fall in CD20 positive cell count to undetectable levels the inhibitor persisted. We discuss the possible reasons for failure of immune tolerance induction and review the literature concerning the use of rituximab for this indication.

Acute lymphoblastic leukaemia of the L3 subtype in adults in the Northern health region of England 1983-99.

AIM: Acute lymphoblastic leukaemia (ALL) with an L3 morphological FAB type is regarded by some as being synonymous with B cell ALL or ALL with a Burkitt-type chromosomal translocation-t(8;14), t(2;8), t(8;22). This paper describes a series from a population based study of 24 patients with L3 ALL presenting over 17 years. METHODS: Clinical data were collected prospectively from all adult patients presenting with acute leukaemia in the Northern region since 1982. Data from all patients diagnosed with FAB type L3 ALL were analysed. RESULTS: Overall, L3 ALL accounts for 8.6% of all adult ALL and it is more common in the elderly than has hitherto been recognised. In addition to classic Burkitt-type translocations (11 of 24 cases), the t(14;18) translocation, which is characteristically found in lower grade lymphomas such as follicular lymphoma, is frequently present (five of 24 cases). CONCLUSION: The presence of L3 ALL is often associated with non-Burkitt-type translocations and the presence of a t(14;18) translocation may indicate that in some cases a clinically non-apparent lymphoproliferative disorder, such as a low grade follicular lymphoma, has transformed to a more aggressive form and, thus, presents as a de novo acute leukaemia.