FLT3 inhibitors as MRD-guided salvage treatment for molecular failure in FLT3 mutated AML.

Patients with FLT3-mutated AML have a high relapse rate and suboptimal outcomes. Many have co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR and those destined to relapse can be identified by high or rising levels of MRD, called molecular failure.  This provides a window for pre-emptive intervention, but there is little evidence to guide treatment. The use of FLT3 inhibitors (FLT3i) appears attractive but their use has not yet been evaluated.  We identified 56 patients treated with FLT3i at molecular failure.  The FLT3 mutation was an ITD in 52, TKD in 7 and both in 3. Over half of patients had previously received midostaurin. Molecular failure occurred at a median 9.2 months from diagnosis and was treated with gilteritinib (n = 38), quizartinib (n = 7) or sorafenib (n = 11). 60% achieved a molecular response, with 45% reaching MRD negativity. Haematological toxicity was low, and 22 patients were bridged directly to allogeneic transplant with another 6 to donor lymphocyte infusion. 2-year overall survival was 80% (95%CI 69-93) and molecular event-free survival 56% (95%CI 44-72). High-sensitivity next-generation sequencing for FLT3-ITD at molecular failure identified patients more likely to benefit. FLT3i monotherapy for molecular failure is a promising strategy which merits evaluation in prospective studies.

Defective T-cell response to COVID-19 vaccination in acute myeloid leukaemia and myelodysplastic syndromes.

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3). Antibodies against SARS-COV-2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T-cell reactivity to SARS-COV-2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response.

Haematology patients and the Internet--the use of on-line health information and the impact on the patient-doctor relationship.

OBJECTIVE: Patients access on-line health information (OHI) to better understand their health. We aimed to determine which demographic factors influence OHI use. We also explored how OHI is used and subsequent implications to the patient-doctor relationship. METHODS: We distributed a self-administered questionnaire to 202 haematology out-patients. RESULTS: 62.3% used the internet and 54.3% used OHI. Higher education, (P<0.001, OR 34.62, 95% CI 5.20-230.66) and household incomes of £15000-25000 (P=0.023 OR 4.8 95% CI 1.236-18.59) were positively associated with OHI use. Those reassured after reading OHI had improved trust in their specialist (P<0.001, OR 52.1, 95% CI 12.3-221.1), improved confidence during consultations, (P<0.001, OR 23.0, 95% CI 2.8-188.2) and were improved decisions makers (P=0.008, OR 13.6, 95% CI 4.1-45.7). Those with increased trust in their haematologist also had improved confidence (P<0.001, OR 6.2, 95% CI 2.2-17.3) and improved decision making ability (P<0.001, OR 13.6, 95% CI 4.7-39.4). 74.6% of patients did not share OHI with their haematologist. CONCLUSIONS: Two-thirds of participants were exposed directly or indirectly to OHI. OHI affects patients' view of their health and influences behaviour during consultations. PRACTICE IMPLICATIONS: Haematologists could facilitate patients using OHI by recommending high quality websites and act supportively when patients share OHI.

NOACs for thromboprophylaxis in medical patients.

The risk of venous thrombosis extends for an indeterminate length of time following admission to hospital with a medical or surgical condition. Observational studies in surgery show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. Large bodies of evidence support the heightened risk status of hospitalised surgical and medical patients, and that prophylactic measures significantly reduce the risk of thrombosis. Extending thromboprophylaxis for 4-6 weeks with anticoagulants both old and new has been shown to be efficacious and safe in surgical patients. However in populations of medical patients although prolonged anticoagulant thromboprophylaxis has been shown to be efficacious it also results in more bleeding and the risk benefit is not clear. Hence no therapies are approved for prolonged thromboprophylaxis in medical patients. In this area there have been one phase III study of low molecular weight heparin and two completed phase III studies of NOACs. This article briefly summarises our understanding of the background to preventing venous thromboembolism in hospitalised medical patients and reviews the details of the studies using NOACs.

The modern management of gout.

Gout is an inflammatory arthritis characterized by self-limiting but excruciatingly painful acute attacks. These are a consequence of monosodium urate (MSU) crystals being deposited within articular or periarticular tissue. Chronic tophaceous gout can develop after years of acute intermittent gout. Recent discoveries, including the role of the inflammasome and intracellular events demonstrating that pro-inflammatory cytokines, IL-1 beta, -8 and TNF-alpha, promote neutrophil influx. Also, genetic advances with the identification of the URAT-1 transporter and genetic variation in SLC 2A9 as a key regulator of urate homoeostasis, have given us deeper understanding of the pathophysiology of gout, and also allow for more targeted treatments. Hopefully, new and emerging therapeutic options will reduce treatment-resistant gout in patients who are unresponsive or unable to take traditional urate lowering therapy. The development of new therapies may also increase patient numbers being treated in the specialist setting, which may have several secondary benefits.