Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL-class fusion.

Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).

Bridging the Gap between Aetiological and Maintaining Factors in Social Anxiety Disorder: The Impact of Socially Traumatic Experiences on Beliefs, Imagery and Symptomatology.

BACKGROUND: A number of key environmental factors during childhood have been implicated in the aetiology of social anxiety disorder (SAD), including aversive social experiences, traumatic life events and parent-child interaction. However, understanding the nature, interactions and relative contributions of these factors remains unclear. Furthermore, the relation of aversive social experiences to the development of key maintaining factors in SAD requires elucidation. AIMS: The current study aimed to extend previous research regarding the aetiology of SAD by investigating the relationship between key environmental factors in childhood, negative beliefs and self-imagery, and the development of SAD. METHOD: Social anxiety disorder individuals (n = 40, 87.5% female, Mage = 20.25 years) completed self-report measures of social anxiety symptomatology, traumatic experiences and parenting style. In addition, participants were administered interviews assessing various domains of childhood trauma, as well as negative self-imagery and associated socially traumatic memories. RESULTS: Participants reported a high frequency of early traumatic experiences across all domains (physical, emotional, sexual, social and non-relational), as well as a high degree of parental overcontrol. However, social anxiety symptomatology was most strongly correlated with socially traumatic experiences, and mediation analyses suggest that appraisal of aversive social/peer experiences accounts for the relationship of SAD symptomatology with negative self-beliefs and imagery. CONCLUSIONS: These outcomes suggest that social trauma may be a key proximal cause of SAD development, leading to the development of negative beliefs and imagery that subsequently maintain the disorder. These findings have implications for understanding SAD aetiology, and improving treatment outcomes for the disorder. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Negative social experiences have been implicated in the development of social anxiety disorder (SAD), but the role of this predisposing factor remains unclear. Compared with other risk factors for SAD, social anxiety symptomatology was most strongly correlated with socially traumatic experiences. Mediation analyses suggested that appraisal of aversive social experiences accounted for the relationship of SAD symptomatology with negative self-beliefs and imagery. These outcomes suggest that SAD individuals would benefit from interventions targeted at processing socially traumatic memories (e.g., imagery rescripting).

The efficacy of imagery rescripting compared to cognitive restructuring for social anxiety disorder.

Imagery rescripting (IR) aims to alter negative meanings associated with distressing autobiographical memories. The current study aimed to extend demonstrated benefits of IR for social anxiety disorder (SAD), including direct comparison of IR with cognitive restructuring (CR) to assess the relative impact of these interventions on symptoms and processes. SAD individuals (N=60) were randomly allocated to IR, CR or Control conditions, and completed two speech tasks (before and after) their assigned intervention. Participants completed measures of symptomatology and state affective/cognitive variables in relation to the intervention and speech tasks. Results support the benefits of IR for SAD, with both IR and CR yielding large and equivalent reductions in trait social anxiety. However, IR and CR may function via differing pathways. Outcomes suggest that IR may be most effective in the treatment of SAD when delivered across multiple sessions or preceded by CR to target verbal and imaginal self-representations.

A systematic review of mindfulness and acceptance-based treatments for social anxiety disorder.

CONTEXT: The cultivation of mindfulness and acceptance has been theoretically and empirically associated with psychological ancillary well-being and has demonstrated efficacy in the treatment of various disorders. Hence, mindfulness and acceptance-based treatments (MABTs) have recently been explored for the treatment of social anxiety disorder (SAD). This review aims to evaluate the benefits of MABTs for SAD. METHODS: Systematic review of studies investigating an MABT for individuals with SAD, using PsycInfo, Medline, PubMed, and Cochrane Central Register of Controlled Trials. RESULTS: Nine studies were identified. Significant improvements in symptomatology were demonstrated following the MABT, but benefits were equivalent or less than yielded by cognitive-behavioral therapy (CBT). LIMITATIONS: The few treatment studies available were compromised by significant methodological weaknesses and high risk of bias across domains. Studies were largely uncontrolled with small sample sizes. The hybrid nature of these interventions creates ambiguity regarding the specific utility of treatment components or combinations. CONCLUSIONS: MABTs demonstrate significant benefits for reducing SAD symptomatology; however, outcomes should be interpreted with caution until appropriate further research is conducted. Furthermore, the benefit of MABTs above and beyond CBT must be considered tentative at best; thus, CBT remains best practice for first-line treatment of SAD.

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience.

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.