Day: December 20, 2022

Categories : Cancer PaediatricsTags :

Extended Chemotherapy Slashes Childhood Leukaemia Recurrence

On By ModernMedia
Photo by National Cancer Institute on Unsplash

Giving three years of chemotherapy to children with acute lymphoblastic leukaemia (ALL) instead of two years lowers the risk of their disease coming back after treatment by three times. The survival rate of all children with ALL, the most common form of childhood cancer, together has further increased to 94%. Less intensive therapy proved safe for three groups of children, resulting in a better quality of life. These findings on a large Dutch study into ALL were reported at the annual conference of the American Society of Hematology (ASH).

Many children with ALL have good outcomes. After two years of chemotherapy treatment, nine out of ten children are cured. But some children have a more aggressive disease, such as having the Ikaros mutation in their leukaemia cells, have a greater risk of recurrence after treatment. In order to improve the chances of survival and quality of life of all children with leukaemia, the treatment protocol has been continuously adapted over the years, based on the latest scientific insights.

Prof Rob Pieters, medical director and paediatric oncologist at the Princess Máxima Center for paediatric oncology in the Netherlands, presented the outcomes of the ALL-11 treatment protocol. The Dutch researchers tested the benefit of an adapted treatment in specific groups of children with leukaemia, including children with the Ikaros mutation. More than 800 children in the Netherlands were treated with this protocol between April 2012 and July 2020.

Threefold lower risk of recurrence

Children with Ikaros leukaemia received an extra year of chemotherapy in the ‘maintenance phase’ on top of the first two years of treatment. This change lowered the risk of their cancer coming back by threefold: this happened in only 9% of them, compared to 26% of the children in the previous treatment protocol.

87% of children with Ikaros leukaemia survived their disease for five years without their cancer coming back, an improvement on the 72% in the previous protocol. Because of the extra year of chemotherapy, this group of children had a slightly higher risk of infection, but these were treatable. The extended therapy did not lead to any additional side effects.

Analysis of data from all children with ALL, regardless of subtype, showed that the five-year survival rate has improved stepwise over the past 30 years from 80% to 94% under the ALL-11 protocol.

Safe reduction of treatment

In the ALL-11 protocol, doctors and researchers also looked at the benefit of a less intensive treatment plan for three groups of children. This included children with a leukaemia mutation linked to a very high chance of recovery, and children with Down syndrome who experience more severe side effects. These children received treatment without or with a lower dose of anthracyclines, a type of leukaemia drug that increases the risk of heart damage and infections. The reduced treatment proved successful: children had the same or even a better chance of survival, while their quality of life improved due to a lower risk of infections and damage to the heart.

Global interest

Globally, there is much interest in the Dutch research as it has been unclear how to improve therapy for children with Ikaros leukaemia. The results have now been presented for the first time at the largest blood cancer conference, and could lead to changes in treatment protocols for these children worldwide.

In the Netherlands, there are about 15 children with ALL each year for whom existing treatments stop working. Since 2019, they have been eligible for treatment with CAR T-cell therapy, a promising form of immunotherapy that now leads to a cure in 40% of these children.

Making a difference

Prof Monique den Boer, medical biologist and group leader at the Princess Máxima Center, played an important role in the adapted therapy for children with the Ikaros gene change. She says: ‘The Ikaros mutation was first discovered about 15 years ago in children with leukaemia who had a poor prognosis, partly thanks to the emergence of new DNA technologies. We saw that the cancer came back in many of these children shortly after the end of the two-year treatment plan. I am very proud that our lab findings have now found their way into the clinic and can make such a big difference for children with leukaemia.”

More cure with fewer side effects

Prof Pieters concludes: The five-year survival rate for children with acute lymphoblastic leukaemia has increased enormously since the 1960s, from zero to 94%, but the last steps are the most difficult. We are now one step closer to curing all children with ALL. We have also largely been able to remove a drug that poses a risk of heart damage from the treatment of children with a less aggressive form of the disease. The latest results for children with leukaemia therefore fit in perfectly with our mission: curing more children with cancer, with fewer side effects.”

Source: Princess Máxima Center

Categories : AntibioticsTags :

In-depth: ‘Access not Excess’ Key to Reducing Antibiotic Resistance in SA

On By ModernMedia

By Tiyese Jeranji

Source: Danilo Alvesd on Unsplash

Antibiotics play a vital role in the management of bacterial infections, reducing morbidity, and preventing mortality. A 2011 report from the United Kingdom estimated that they have increased life expectancy by 20 years. However, the extensive use of antibiotics has resulted in drug resistance that threatens to reverse their life-saving power and if the situation is not reversed, it has been estimated that by 2050, 10 million people will die annually of drug-resistant infections.

Such estimates of future deaths are obviously uncertain, but there is strong evidence the problem is already very serious. A major study published earlier this year in the Lancet estimated that globally around 1.27 million deaths in 2019 were directly due to antibiotic resistance. The study identified sub-Saharan Africa as the hardest-hit region.

What is AMR?

Sham Moodley, a community pharmacist from Durban and the vice chairperson of the Independent Community Pharmacy Association (ICPA) explains that antimicrobial resistance (AMR) is the ability of microorganisms (bacteria, viruses, fungi, and protozoa) to withstand treatment with antimicrobial drugs. “It is vitally important as it directly impacts our ability to treat and cure common infectious diseases, including pneumonia, urinary tract infections, gonorrhoea and tuberculosis,” he says.

According to Professor Olga Perovic, Principal Pathologist at the National Institute of Communicable Diseases’ Centre for Healthcare-associated Infections, Antimicrobial Resistance and Mycoses (CHARM), there are six factors fuelling the AMR crisis. These are over-prescribing and dispensing of antibiotics by health workers, patients not finishing their full treatment course of antibiotics, poor infection control in hospitals and clinics, lack of hygiene and poor sanitisation in the community, lack of new antibiotics being developed, and the overuse of antibiotics in livestock and fish farming.

Under overuse, she stresses the misuse of antibiotics to treat upper respiratory tract infections, which are typically viral rather than bacterial. Antibiotics are powerless against viruses. Another driver of inappropriate or overprescribing of antibiotics, she says, may be the lack of testing of specimens for the presence of bacteria and their susceptibility to treatment.

How can we prevent AMR?

Dr Marc Mendelson, Professor of Infectious Diseases and Head of the Division of Infectious Diseases and HIV Medicine at Groote Schuur Hospital, the University of Cape Town as well as chairperson of the Ministerial Advisory Committee on Antimicrobial Resistance, says reducing the use of antibiotics is about preventing the need for prescription in the first place. (Mendelson’s recent SAMJ article provides excellent further reading on AMR in South Africa.)

“So, reducing the burden of infections through the provision of clean water and safe sanitation (reduces diarrhoeal diseases) and vaccination programmes (reduces diarrhoea and pneumonia for instance),” he says. “Education and awareness raising of the public and (sadly) healthcare professionals as to the correct use of antibiotics is also critical.”

Broadly speaking, all the experts we interviewed agreed that we should use far fewer antibiotics and only use them when they are absolutely necessary. But actually making this happen is surprisingly complex.

Part of the complexity, for example, is that resistance profiles and disease profiles are different in different places. Geraldine Turner, a pharmacist at Knysna Hospital in the Western Cape, says there is a need for guidelines tailored to the South African context or linked to the local epidemiology. This, she says, can play an important role in determining the correct antibiotics to be used.

It is also not just an issue of what antibiotics are prescribed for humans.

“A big driver of antimicrobial resistance is overuse in agriculture and collaboration with stakeholders in this regard is required,” says Turner. She says we need policies that facilitate improved integration among environmental, animal, and human sector interventions.

Moodley agrees that a multidisciplinary, One Health approach is needed at every level of care and in both human and animal health sectors.

“It is important we reinforce the principle that antimicrobial medicines for human use are only supplied on the authority of a healthcare professional and that antimicrobial medicines for either human or animal use are only supplied in accordance with country legislation and regulations,” he says.

The role of stewardship programmes

One response to the AMR crisis is antimicrobial stewardship programmes or ASPs. Moodley describes ASPs as a systematic approach used “to optimise appropriate use of all antimicrobials to improve patient outcome and limit the emergence of resistant pathogens whilst ensuring patient safety.”

Perovic says, “In healthcare institutions, resistant bacteria can spread easily within and from patient to patient. That is why there are guidelines, which we call ASPs in the medical and veterinary fields, on how and when antibiotics are prescribed as well as how to implement infection prevention and control measures, particularly for patients with health risks such as diabetes, high blood pressure, and cancer.”

“In hospitals,” explains Mendelson, “ASPs will consist of a governance body such as an AS Committee that directs a work programme of stewardship, often with AS teams as the implementers of policy. AS teams can involve anything from single pharmacists or physicians, through one to two dedicated individuals, through to all-singing all-dancing multi-disciplinary teams in academic teaching hospitals, comprising infectious diseases specialists, microbiologists, pharmacists, [and] infection prevention and control nurses.”

ASPs are not only important at institutional levels, adds Moodley, but imperative for every individual prescriber/practitioner to implement to reduce AMR in our population.

Critical role for pharmacists

Mendelson stresses that pharmacists are integral to antibiotic stewardship in South Africa and globally. “Community pharmacists give advice to patients seeking symptomatic relief and reduce doctors’ visits, which can result in antibiotic prescriptions when not needed,” he says. In hospitals, dispensing pharmacists help optimise the antibiotics prescribed to patients by checking indication for the antibiotic, dose, dosing frequency, and duration. “Some hospitals have pharmacists on the wards, again, checking and helping to optimise the use of antibiotics,” he says.

“Pharmacists play an important role in recommending symptomatic treatments for non-specific symptoms and particularly, the common cold, which is a major cause of inappropriate antibiotic prescribing, requiring simple paracetamol with or without decongestants. Unfortunately, a recent pilot study suggests that a small number of community pharmacies are dispensing antibiotics without a prescription, which is not allowed in South Africa,” says Mendelson.

Turner concurs that pharmacists play a crucial role in ensuring that the correct antibiotics are used appropriately and only if indicated. She says pharmacists are also in a good position to counsel and advise patients on the correct use of antibiotics.

Strategy framework

The key policy document setting out South Africa’s response to AMR is the South Africa Antimicrobial Resistance Strategy Framework of 2018-2024. The framework outlines nine strategic objectives – they include improving the appropriate use of diagnostic investigations to identify pathogens, guiding patient and animal management and ensuring good quality laboratory, enhancing infection prevention and control, promoting appropriate use of antimicrobials in humans and animals as well as legislative and policy reform for health systems strengthening.

Mendelson is positive about what has been achieved so far. “There have been major improvements to the surveillance and reporting of antibiotic resistance and antibiotic use in humans and animals, development of a greater one health (human, animal, and environmental health) response. There was a formation of national training centres for antibiotic stewardship and empowerment of under-resourced provinces to train and develop Antimicrobial Stewardship programmes and there have been improvements in governance and delivery of infection prevention and control measures in hospitals and development of education programmes for healthcare workers in South Africa,” he says.

But Mendelson also says that challenges remain in promoting prescribing behaviour change amongst the health workforce in SA and the expectations and social position that antibiotics hold in society.

As with several other health policies, there are questions on whether the plan has been backed up with funding.

“The national strategic framework remains largely unfunded (shared by most low- and middle-income countries) but this does hamper progress in developing programmes of interventions,” says Mendelson. “In food production, reducing [the] use of antibiotics is an important goal but will require investment in reducing drivers of infection in the animals that produce food. Legislation to bring all antibiotic prescribing in food production under veterinarian control will be an important intervention,” says Mendelson.

Source: Spotlight