Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.     

CAR-T cell therapy in paediatric acute lymphoblastic leukaemia – past,present and future

Over the last decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising treatment modality for relapsed/refractory B-cell malignancies in both children and adults. As an adoptive immune therapy, CAR-T cells have the potential to overcome disease that is resistant to chemo- and radiotherapy as well as represent a viable option for those who have already reached toxicity ceilings with standard therapies. CD19-directed CAR-T cell products have been licensed for use in paediatric B-cell acute lymphoblastic leukaemia that is refractory, in relapse post-transplant or in second or later relapse. Many challenges remain, rightly resulting in a heavily-mined research field. These include mitigating short-term immune-mediated toxicity, maintaining durability of responses, broadening treatment accessibility and extending its applicability to other malignant settings. In this review, dedicated to marking 60 years since the establishment of the British Society for Haematology, we will focus on the contribution of our community towards the success of CD19-directed CAR-T cell therapy in children. We will put current practice in CAR-T cell therapy into the context of future challenges to be addressed in order for it to fulfil its “game-changing” therapeutic potential.     

Clinical importance of main pancreatic duct variants and possible correlation with pancreatic diseases

Abstract

Background: Except for pancreas divisum (PD), the prevalence of anatomic variants of the main pancreatic duct (MPD) seems to be insufficiently investigated. To date, their role in the occurrence of pancreatic exocrine insufficiency (PEI) and morphological changes suggestive of chronic pancreatitis (CP) has remained unclear.

Methods: A systematic review was performed, searching MEDLINE and Web of Science, limited to articles published between 1960 and 1 June 2019.

Results: Our review included a total number of 3234 subjects. The most common variant of MPD was type 3, followed by type 1, indicating MPD drainage pattern into major papilla (MP) as the most frequent. A sub-variant of type 3, known as ‘reverse pancreas divisum’ had a prevalence of 2.2%. Type 4 variant- PD, was found in 6.4% of all cases. The most common sub-variant of PD was complete PD, followed by incomplete PD and variant with MPD as only pancreatic duct. Type 5 variant (including ansa pancreatica) was present in 2.9% of subjects. Apart from one study with a significantly higher frequency of morphological changes suggestive of CP in patients with ansa pancreatica, the studies stated no significant association between pancreatic disease and MPD variants. Furthermore, only one study examined the influence of MPD variants on exocrine pancreatic function. Although equivocal, this association is most likely found to be insignificant.

Conclusion: To elucidate linkage between MPD variants and the occurrence of chronic pancreatitis and impairment of pancreatic exocrine function, further clinical investigations are warranted.     

The impact of premature birth on dental maturation in the permanent dentition

Clinical Oral Investigations - To evaluate tooth development and calculate dental maturity score in prematurely born children and to compare the findings with full-term born children. Nine-year-old...