Call for better adherence to international best practice in MPN
Australian haematologists have a bone to pick with peers after their review of the Australian Cancer Atlas suggested not everyone has been following international best practice.
Central Coast Haematology clinical haematologist Dr Cecily Forsyth and colleagues wrote to the Internal Medicine Journal after noting “marked variation in the reported incidence of [classical myeloproliferative neoplasms (MPN)], not only between states but also between regions in close proximity that share similar demographics”.
In particular, they noted a “striking difference” between regions either side of New South Wales’ Hawkesbury River — where the reported incidence ranged from 33% below to 4% above the national average in greater Sydney and 6% to 32% above the national average in the Central Coast/Hunter region.
They felt the disparity was unlikely to be due to a real difference in MPN incidence in this region and more likely “[reflected] variation in the practice of performing bone marrow biopsies at diagnosis as well as inconsistent symptoms to capture any MPN patients who have not had biopsies”.
Histological cancer diagnosis is typically needed for inclusion in state-based cancer registries and a morphological bone marrow diagnosis “is a major criterion in the 2016 World Health Organization (WHO) classification of all Philadelphia-negative MPN,” Dr Forsyth and co wrote.
“It is surely time for all Australian haematologists to follow international best practice and perform [bone marrow] biopsies at diagnosis on patients with MPN.”
“When this is done, if the variation in the incidence of MPN between geographical regions in Australia persists, then environmental or other causes will need to be carefully considered,” they concluded.
Novel thrombolytic may be alternative to tPA in stroke
A novel thrombolytic drug known as caADAMTS13 variant represents a potentially viable therapeutic option for the treatment of acute ischaemic stroke, according to UK researchers.
A team at Manchester University developed the candidate molecule based on the enzyme ADAMTS13, which is secreted into the blood and reduces the action of von Willebrand factor.
When tested in animal models with artificially induced thrombus formation, caADAMTS13 significantly reduced the von Willebrand factor protein and fibrin deposits in the middle cerebral artery. It also induced a significant dissolution of platelet aggregates and a reduction in the resulting tissue hypoperfusion,
“Our novel drug is able to break down the blood clots that are resistant to the current treatment tPA [recombinant tissue plasminogen activator]. In doing so, more stroke patients could show recovery of function than at present,” said study investigator Professor Stuart Allan.
“Clearly there is still some way to go, and we need to know if the drug is effective a period of time after the stroke has occurred – with less risk of haemorrhage. We are optimistic that we will be able to show this drug can do that; once we have, we hope to move onto human trials. It’s very exciting.”
The findings are published in Blood.
Checkpoint inhibitor efficacy impaired by PPIs
Proton pump inhibitors (PPIs) may reduce the effectiveness of some immune checkpoint inhibitors (ICI) by causing gut dysbiosis, Australian researchers say.
A retrospective review of outcomes for 1202 lung cancer participants in the IMPower150 trial of immunotherapies found that PPI use was independently associated with worse Overall Survival (Hazard 1.53 [1.21–1.95], P < 0.001) and Progression Free Survival (1.34 [1.12–1.61], P = 0.002) in patients treated with atezolizumab.
PPI use also had a negative effect in patients treated with atezolizumab and bevacizumab plus carboplatin plus paclitaxel (BCP), but not BCP alone.
Lead author Dr Ash Hopkins from the Flinders Health and Medical Research Institute, Adelaide, said it was important to understand the impacts of PPIs since about 30% of cancer patients use them, and usually for extended periods of time.
“Of concern is that the medication is often overused, or used inappropriately, as it is seen to cause little harm, however our research could indicate a need to change this approach,” said Dr Hopkins, a NHMRC Investigator Fellow and leader of the Clinical Cancer Epidemiology Lab at Flinders University.
He suggested the effect may be mediated via the gut microbiota as it plays an important role in regulating immune function.