Oxford University Hospitals NHS Foundation Trust is an English teaching hospital and part of the Shelford Group. It is one of the UK's largest teaching hospitals and one of the largest hospitals in Europe. The Trust is made up of four hospitals – the John Radcliffe Hospital (which includes the Children's Hospital, West Wing, Eye Hospital, Heart Centre and Women's Centre), the Churchill Hospital and the Nuffield Orthopaedic Centre, all located in Oxford, and the Horton General Hospital in Banbury, north Oxfordshire.As well as the four main hospitals, the trust also provides services in four community hospitals across Oxfordshire including Thame, Wallingford, Wantage and Witney. The services offered at these community hospitals are fairly basic and differ from hospital to hospital. Wantage community hospital is also accompanied by Wantage health centre whereby additional health services are provided by the trust. Other clinics and health centres serviced by the trust in Oxfordshire includes Bicester and Oxford with the trust also providing some services in clinics and hospitals in neighbouring counties.
In these two cases, we highlight the concept of pregnancy-associated thrombotic microangiopathy (TMA) overlap syndrome, where two different TMAs occur together, likely one driving another. Thrombotic microangiopathies occurring in pregnancy threaten the lives of both mother and fetus, and yet precise diagnosis may be difficult because of overlapping clinical and laboratory features. The three main syndromes to be considered are thrombotic thrombocytopenic purpura (TTP) - an acute disorder caused by severe ADAMTS13 deficiency; preeclampsia/HELLP syndrome - characterised by haemolysis, elevated liver enzymes, and low platelets; and atypical haemolytic uremic syndrome (aHUS)- most commonly caused by mutations in the complement regulatory genes. We present two cases where the combination of two TMAs (one most likely driving the other) led to difficult management dilemmas.
Background: There are multiple effective treatment options for patients diagnosed with chronic lymphocytic leukemia and small lymphocytic lymphoma (hereafter, simply CLL). In 2025, two phase 3 randomized clinical trials of pirtobrutinib, a non-covalent BTK inhibitor, were reported, demonstrating improved outcomes versus comparator therapies in the treatment-naïve setting (NCT05254743 and NCT05023980). Methods: A systematic literature review was conducted to identify RCTs in the first-line setting for CLL. A Bayesian NMA was performed to compare overall response rate (ORR) and progression-free survival (PFS) of pirtobrutinib versus treatments recommended by the National Comprehensive Cancer Network in the first-line setting, with a focus on BTKi monotherapy. Results: Eight unique trials were identified for comparison versus pirtobrutinib. Eligible RCTs formed two disconnected networks (pirtobrutinib, ibrutinib and zanubrutinib were in Network 1; acalabrutinib was in Network 2). Results from Network 1 for ORR showed an odds ratio (OR) = 0.56 (95% credible interval [CrI], 0.28, 1.12) for ibrutinib versus pirtobrutinib and OR = 0.50 (95% CrI, 0.20, 1.27) for zanubrutinib versus pirtobrutinib. The PFS of ibrutinib was inferior to pirtobrutinib (hazard ratio (HR) = 1.89, 95% CrI, 1.13, 3.19); the PFS HR comparing zanubrutinib with pirtobrutinib was 1.51 (95% CrI, 0.84, 2.72). Conclusions: This NMA shows that pirtobrutinib has better PFS outcomes than ibrutinib. While PFS outcomes suggest that pirtobrutinib is comparable to second-generation covalent BTKi monotherapies, uncertainty exists in the interpretation of the treatment effect, as evidenced by wide credible intervals. These findings suggest the value of pirtobrutinib as a future treatment option for patients in the first-line setting.
Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies that have a natural history that follows a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy with or in combination with chemotherapy (chemoimmunotherapy), with second-line options such as covalent (c) Bruton tyrosine kinase inhibitors (BTKi). However, management of relapsed and refractory (R/R) MZL remains a challenge. Pirtobrutinib, a highly selective, non-covalent BTKi has shown promising efficacy and tolerability in patients with poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here we report the safety and efficacy of pirtobrutinib in patients with MZL from the phase 1/2 BRUIN study. Endpoints included investigator assessed ORR by Lugano 2014 criteria, DOR, PFS, OS, and safety. Among 36 R/R MZL patients (EMZL: n=6; NMZL: n=17; SMZL: n=13), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10) including anti-CD-20 antibody (100%), chemotherapy (86%) and cBTKi therapy (72%). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1) including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95%CI, 7.4-non-estimable [NE]), and median PFS was 16.6 months (95%CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0, 41.3), median OS was NE (95%CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95%CI, 33.4-73.4). Pirtobrutinib was well-tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to TEAEs in 4 (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pre-treated R/R MZL, including prior cBTKi. NCT03740529
Congenital dyserythropoietic anaemia type-I (CDA-I) is a rare autosomal recessive disease characterised by ineffective erythropoiesis, haemolysis and non-haematological developmental abnormalities. Its treatment is multifactorial, including the management of anaemia, iron overload and prevention of osteoporosis. The only treatment specific to CDA-I is subcutaneous interferon alpha (IFNα) 2A. This study presents the first summary of all published cases of CDA-I patients (n = 33) treated with IFNα and categorises their outcome. We also present new unpublished cases (n = 7). Overall, we find that IFNα administration causes a statistically significant mean increase in haemoglobin of 30.7 g/L (p < 0.001). However, we note that previous studies do not assess the impact of IFNα therapy on providing symptomatic benefit to patients with CDA-I, or the weight of side effects on their quality of life. We collaborate directly with patients through the organisation Congenital Anaemia Network to establish patient preferences regarding IFNα treatment. We propose a classification framework for the use of IFNα in CDA-I that includes patient-reported outcome measures in addition to grading response according to changes in Hb levels. We believe that the use of this framework will aid standardisation in measuring response to therapy, improve clinical practice and assist in future research.
