Tag: leukaemia

Promising Drug Combination for Multiple Myeloma Treatment

Depiction of multiple myeloma. Credit: Scientific Animations

Researchers in Ireland have found that venetoclax, a medication currently approved for leukaemia, has benefits for patients with multiple myeloma when used in combination with another drug. This discovery offers a new avenue of treatment options for the currently incurable disease.

A type of blood cancer, multiple myeloma (MM) is still incurable despite treatment recent advances. The search for innovative treatment strategies is crucial, particularly for patients whose cancer is resistant to standard care.

In the new study published in Haematologica, researchers at the RCSI Department of Physiology and Medical Physics and the Beaumont RCSI Cancer Centre set out to identify complementary drugs that would enhance the efficiency of venetoclax, a drug approved for use in leukaemia, for MM treatment.

Although previously tested in MM, venetoclax, which blocks the function of a protein called BCL-2, was only found to be effective for a small proportion of patients.

The researchers discovered that combining venetoclax with a drug called 5-azacytidine significantly increased its effectiveness across many MM cell lines, indicating a broader potential patient population that could be treated with the new combination.

“This research is a significant step in identifying more effective treatment options for multiple myeloma. By combining venetoclax and 5-azacytidine we’ve seen enhanced efficacy across a wide range of patient samples. It shows the benefits of re-evaluating existing treatments in new contexts to expand their potential.” said Professor Tríona Ní Chonghaile, Associate Professor and research lead, Department of Physiology and Medical Physics.

Professor Siobhán Glavey, Chair, RCSI Department of Pathology and Clinician Scientist, Beaumont RCSI Cancer Centre commented: “Discovering the potential of this new drug combination is a promising development. Our next goal is to test for efficacy and safety for multiple myeloma in a clinical trial setting to bring us closer to offering a new treatment strategy for patients.”

The mechanism of how the two drugs work efficiently together was also investigated and it was shown that the combination of the two therapies was effective in patient samples from different stages of cancer, even if that patient had been previously treated with chemotherapy drugs.

The research was conducted in collaboration with the Department of Haematology, Beaumont Hospital, Dublin; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; and the Department of Medicine/Haematology, University of Galway, Galway.

This study was supported by funding from Leukemia Research Foundation, Breakthrough Cancer Research and AbbVie.

Source: RCSI

Clues to Ponatinib’s Deadly Side Effects could Make it a Safer Cancer Drug

Pexels Photo by Freestocksorg

For some leukaemia patients, the only potential chemotherapy option is ponatinib, a drug that also carries a high risk of heart failure. This means that some patients who recover from their cancer will end up dying of heart disease brought on by the cure.

In a new study, researchers from the University of Illinois Chicago and other universities have identified mechanisms that cause ponatinib to harm the heart. They also identified a promising treatment that could reverse this process.

The paper, with senior author Sang Ging Ong, assistant professor of pharmacology and medicine at UIC, is published in Circulation Research. The study is part of a growing field called cardio-oncology that investigates drugs that shrink tumours but can also cause heart problems.

While there are three options of drugs for treating chronic myeloid leukaemia, many patients are resistant to the other two, leaving ponatinib as their only choice.

“These patients have no other options for treatment,” Ong said, despite the concerns about the drug’s side effects.

In fact, ponatinib was pulled from the market for a few months after its introduction in 2012 because of concerns about heart problems.

The researchers were interested in understanding the interaction between ponatinib and the heart cells responsible for contraction.

They discovered that ponatinib damages these cells by activating a process known as the integrated stress response.

The mechanism for this is related to the functioning of a kinase (an enzyme involved in energy transfer) called GCN2.

The researchers found that ponatinib, despite being a kinase inhibitor, actually activates GCN2, which in turn switches on the integrated stress response.

While this response isn’t always a bad thing, normally protecting cells, it can also lead to their death under prolonged stress.

To see if this response was harming the cells, the researchers studied what would happen if they used a small molecule to block the integrated stress response in both cells and in mice during ponatinib treatment.

They found that the treatment helped protect heart cells from the damaging side effects of the drug yet did not diminish ponatinib’s tumour-fighting efficacy.

“It protects the heart but at the same time, it still allows us to kill cancer cells,” Ong said.

More research is needed to know if this protective measure would work well in humans, Ong said.

The mechanisms they identified are important in other cardiac diseases, as well, which could lead to future research on how to protect cells against different conditions.

Source: University of Illinois Chicago

Conquering Childhood Leukaemia: How You can Help

Preshthi Ishwarlal

Receiving the news that their child has been diagnosed with cancer is devastating for any parent, but this is even worse when they hear that, after 18 months of remission, their little one will need to battle the disease all over again.

This was the case for mom of two Arthie Ishwarlal. Back in 2021, her then two-year-old daughter, Preshthi, was diagnosed with Acute Lymphoblastic Leukaemia (ALL), a type of blood cancer that affects the bone marrow, white blood cells, red blood cells, and blood platelets. But, despite undergoing inpatient treatment, Preshthi experienced a relapse earlier this year with doctors saying that her only chance for survival is a stem cell transplant from a matching donor. Unfortunately, however, there is no match for her on the country’s stem cell registry at present.

As the world observes International Childhood Cancer Day (ICCD) on 15February, Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa explains that South Africans can potentially save Preshthi’s life. While there are currently over 73 000 donors on the South African registry, each only has a 1 in 100 000 chance of being a match for a blood cancer patient in need. But exacerbating the situation for little Preshthi is the lack of Indian donors since the best chance of a match comes from within one’s own ethnic group.”

She adds that it is not just Preshthi who needs a stem cell transplant for a second chance at life. “This is often the only treatment offering children with other blood cancers, like lymphomas, any hope of a cure.”

With leukaemia and lymphomas being two of the five most common cancers among South Africa’s youth, with the former accounting for 34% of childhood cancer cases and the latter 11%, Mokomele urges South Africans aged between 17 and 55 who are in good general health to register as donors. “In doing so, you might save a child’s life.”

Register at https://www.dkms-africa.org/register-now. Registration is entirely free and takes less than five minutes.

For further information, get in touch with DKMS Africa at 0800 12 10 82.

Resounding Success for New Personalised Treatment for Adult Leukaemia

Photo by Tima Miroshnichenko on Pexels

Personalised treatment for the most common form of adult leukaemia helps patients survive for longer and stay in remission, a phase III trial has found. The trial, by the University of Leeds, has been identified as groundbreaking research by the New England Journal of Medicine and the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, where the results were presented.

The data shows that the duration of therapy can be individualised for each patient by using regular blood tests to monitor their response. In the trial, this approach resulted in significant improvements in both progression-free and overall survival in patients with previously untreated chronic lymphocytic leukaemia (CLL). The effect was stronger among patients with poorer outcomes to standard treatments, such as those with some genetic mutations.

Adult patients were given a combination of cancer growth blocking drugs over varied durations depending on how rapidly their disease responded.

The trial found that this approach significantly improved progression-free and overall survival compared to the standard treatment for CLL, with more than 19 in 20 patients in remission three years after starting treatment.

The study, named FLAIR, is a phase III randomised controlled trial for untreated CLL, taking place in more than 100 hospitals across the UK.

Lead author Peter Hillmen, Professor of Experimental Haematology in the University of Leeds’ School of Medicine, and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust, said: “Our findings show that, for this group of patients, the treatment is very effective at tackling their disease and is well tolerated by them. This means that patients on our trial had better outcomes while also enjoying a better quality of life during their treatment. Most patients treated with the new combination have no detectable leukaemia in their blood or bone marrow by the end of treatment which is better than with previous treatments and is very encouraging.”

Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said: “We are delighted to see these results from the FLAIR trial which show the importance and effectiveness of tailoring cancer treatment to the individual patient. Not only this, but the trial has found a way to do so without requiring frequent bone marrow tests which are more invasive and can be painful.

“The collaborative effort that went into this trial – involving researchers, healthcare professionals, funders and dedicated patients and their families – point to a new standard of care which could see real progress made against leukaemia.”

Chronic lymphocytic leukaemia is a type of cancer that affects the blood and bone marrow. It cannot usually be cured but can be managed with treatment. More than nine in 10 people are aged 55 and over when they are diagnosed.

Current treatments include chemotherapy, immunotherapy, or cancer growth blockers.

The FLAIR trial tested cancer growth blockers called Ibrutinib and Venetoclax (I+V), which are usually administered either continuously or for the same fixed duration rather than tailored to each patient’s response. This means that many patients may stop treatment too early, missing the full potential benefit from their therapy or continue therapy for longer than necessary. This could lead to a greater chance of relapse of their leukaemia and/or of treatment side effects.

FLAIR researchers aimed to discover whether it was possible to personalise I+V treatment duration for patients based on regular blood sampling and / or bone marrows, and whether this was as effective or better than standard treatment (FCR).

This regular blood and bone marrow monitoring gave researchers a more up-to-date picture of how patients were responding to I+V, and meant that the duration of I+V treatment could be tailored accordingly to each patient. In addition, it was found that basing the duration of treatment on less invasive, quicker blood samples was just as effective as using bone marrows, which can be painful and sometimes require sedation.

FLAIR was launched in 2014, recruiting 1509 patients with CLL. They were randomised to four treatment groups, each receiving a different treatment.

This part of the FLAIR trial compared two of the groups, placing 260 patients on I+V and 263 on the standard treatment, known as FCR. Almost three quarters were male, which was to be expected as CLL occurs more frequently in males. The average age was 62, and just over a third had advanced disease.

At the end of this stage of the trial, 87 patients had seen their disease progress, 75 of which were on FCR, and 12 on I+V.

To date, 34 of these patients have died during the trial. Of these, 25 were treated with FCR and only nine with I+V.

The patients on I+V underwent blood tests and bone marrows to monitor their response to treatment. The technique used is known as measurable residual disease (MRD) which allows clinicians to see the number of remaining cancer cells. The number of cells may be so small that the patient is asymptomatic. An MRD positive test result means that there are remaining cancer cells.

The research team now hope that this more personalised therapy approach, guided by blood test monitoring will be adopted as a new standard of care for patients needing first line CLL treatment.

Professor Hillmen said: “The results of the FLAIR Trial, led by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds, are exceptional and herald a change in the way chronic lymphocytic leukaemia will be treated. FLAIR has been a huge collaborative effort over the last decade by the UK’s leading CLL specialists and by the haematology teams in over 100 hospitals throughout the UK. The participation of patient groups, individual patients and their families were critical to delivering such progress particularly through the challenges of the pandemic.”

The trial was co-ordinated by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds. Deputy Director Professor David Cairns said: “The vision of the Leeds Cancer Research UK CTU is to improve the length and quality of survival for cancer patients on a worldwide scale. Our strategy to do this is to ensure that we build evidence to identify the correct treatment, for the correct duration, for the correct patient. FLAIR is a trial well aligned to our strategy, and reflects team science including clinicians, laboratory scientists, methodologists and operational experts working together to deliver important trial results. None of this would be achieved without the selfless commitment of trial participants who contribute their time and data.”

The FLAIR trial was funded by Cancer Research UK, Janssen Research & Development, LLC, and AbbVie Pharmaceutical Research and Development.

Source: University of Leeds

CRISPR-Cas9 Gene Editing may Unleash Cancer Cell Resistance

CRISPR-Cas9 is a customisable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way. Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH

Researchers from the Karolinska Institutet in Sweden have identified potential pitfalls in the use of the gene editing technique CRISPR-Cas9, a gene scissors that is used for cancer treatments. Their findings are published in Life Science Alliance.

The study has identified that a cancer cell line, derived from leukaemia, removes a region that encodes a tumour-suppressing gene and genes that control cell growth.

“We found that this elimination often occurs when cancer cells are exposed to stress, such as when using CRISPR, gene scissors, or other treatments such as antibiotics. The elimination changes gene regulation in a unique way, which in turn affects basic biological processes such as DNA replication, cell cycle regulation, and DNA repair,” says Claudia Kutter, research group leader at the Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet.

This knowledge is important for researchers, clinicians, and biotechnologists to correctly interpret and apply gene editing results. The study also has clinical relevance, as the observed eliminations are in genes associated with cancer, which has implications for cancer research and treatment.

“Shockingly, this elimination has been unintentionally overlooked by many researchers who modify genes in cancer cells by CRISPR screenings. The elimination also occurred more frequently in patients who have undergone cancer treatment. The treated cancer cells had, due to the elimination, a selective advantage, which is bad for the patient’s long-term survival as these cells remained after the treatment,” says Claudia.

“The study mainly serves as a warning signal, but also opens doors for further research aimed at harnessing the potential of gene editing while minimising unintended consequences,” Claudia concludes.

Source: Karolinska Institutet

Study Confirms Link between CT Scans in Young People and Increased Risk of Cancer

Credit: Pixabay CC0

A multinational study of almost one million individuals confirms a strong and clear association between radiation exposure from CT scans in young people and an increased risk of blood cancers. These results, published in Nature Medicine, highlight the importance of continuing to apply strict radiological protection measures, particularly in paediatric populations. 

The benefits of computed tomography (CT) for imaging in patient management (including diagnostic efficacy, treatment planning and disease follow-up) are undisputed. But in recent decades the extensive use of this procedure has raised concerns about the potential cancer risks associated with exposure to ionising radiation, particularly in young patients.

“The exposure associated with CT scans is considered low (less than 100mGy), but it is still higher than for other diagnostic procedures,” says Elisabeth Cardis, Head of the Radiation Group at ISGlobal and senior author of the study. Previous studies have suggested an increased risk of cancer in in children exposed to CT scans, but they had several methodological limitations.

To address these limitations, clinicians, epidemiologists and dosimetrists from nine European countries (Belgium, Denmark, France, Germany, Netherlands, Norway, Spain, Sweden, and UK) came together to conduct a multinational, European-funded study, EPI-CT, coordinated by the International Agency for Research on Cancer (IARC).

“Implementing this large, multinational study was challenging – it involved extracting data from radiology records of 276 hospitals and linking them to population-based registries in nine countries, all while maintaining the confidentiality of the individuals’ data,” says Cardis.

A dose-dependent association

The study analysed data from almost one million people, who underwent at least one CT scan before the age of 22. The dose of radiation delivered to the bone marrow, where blood cells are produced, was estimated for each person. By linking this information to national cancer registries, EPI-CT researchers were able to identify those who developed a blood cancer over time. Individuals were followed for an average of 7.8 years, although for those who had CT scans in the early years of the technology, researchers were able to monitor cancer incidence for more than 20 years after the first scan.

The results show a clear association between the total radiation doses to the bone marrow from CT scans and the risk of developing both myeloid and lymphoid malignancies. A dose of 100mGy approximately tripled the risk of developing a blood cancer. These results suggest that a typical scan today (with an average dose of about 8mGy) increases the risk of developing these malignancies by about 16%. “In terms of absolute risk, this means that, for every 10 000 children who have a CT scan, we can expect to see about 1–2 cases of cancer in the 12 years following the examination,” says first author Magda Bosch de Basea, ISGlobal researcher at the time of the study.

The authors point out that more work is needed to ensure that doses and technical parameters are systematically and adequately collected in the clinics in real time to further improve risk estimates in the future.

Public health implications

Today, more than one million children in Europe undergo CT scans every year. Although radiation doses from CT scans have decreased substantially in recent years, the findings of this study underline the need to raise awareness among the medical community and to continue to apply strict radiation protection measures, especially in the youngest patients. “The procedure must be properly justified – taking into account possible alternatives – and optimised to ensure that doses are kept as low as possible while maintaining good image quality for the diagnosis,” Cardis explains. 

Source:

New Drug Effective for 3 of 4 Trial Patients with Relapsed Blood Cancer

Photo by National Cancer Institute on Unsplash

A new targeted drug, may offer a new treatment option for patients with blood cancers, including chronic lymphocytic leukaemia (CLL) and Non-Hodgkin lymphoma (NHL) whose disease has stopped responding to standard treatments.

In the first clinical trial of this drug in humans, nemtabrutinib was effective in three-fourths of cancer patients tested, without severe side effects. The results of the trial were published in the journal Cancer Discovery.

Haematologist and study lead investigator Jennifer Woyach, MD, notes that about half a dozen drugs are available to treat these B-cell cancers. Although most patients respond to these drugs initially, over time, many patients experience disease progression. The study was done by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

“Blood cancers that have relapsed after initial treatments can be difficult to treat, and even with our effective medications, some patients run out of standard treatment options.  In this trial, nemtabrutinib looks very promising for patients whose cancer has progressive after other treatments.” said Woyach, who is co-leader of the Leukemia Research Program at the OSUCCC – James.

How this drug therapy works

When an antigen, such as a virus or bacteria, enters the bloodstream, it triggers a set of signals in B-cells to produce antibodies. In some people, said Woyach, this process goes haywire. Instead of fighting infections, the B-cells begin to divide uncontrollably, resulting in cancer. Drugs against B-cell cancers work by binding to a key enzyme, called Bruton’s tyrosine kinase (BTK). This enzyme is involved in the signaling process. The drugs block the action of the enzyme, and as a result, the abnormal B-cells die.

In many patients, this effect is temporary with available drugs. Over time, the BTK enzyme to which the drugs bind mutates so they can no longer stop its action. Soon, the cancer returns. Nemtabrutinib was designed to bind to BTK even in the presence of common mutations that make other BTK inhibitors stop working. It also binds to a number of proteins besides BTK that are important in B cell cancers. These two properties made this drug very appealing to study in this patient population.

Study methods and results

The researchers tested the new drug on 47 patients who have had at least two prior therapies for their blood cancer. Over half of these patients had relapsed CLL, while the others had NHL. The researchers gave these patients one pill of nemtabrutinib every day, with different doses along the trial. They observed the patients’ response to the drug over time and monitored them for side effects.

The study found more than 75% of the patients with relapsed CLL responded to the drug, at an optimal dose of 65mg. These included patients who had mutations in BTK. Most patients remained cancer free for at least 16 months during the trial. While all patients experienced some side effects – which is common with chemotherapeutic drugs – many of these were minor and manageable, proving that the drug was also very safe.

“The drug is being moved to larger and more definitive trials, where it will be compared against other standard-of-care drugs, and in combination with other active medications,” said Woyach.

The blood cancers investigated in this trial affect B lymphocytes, which is a cell that is responsible for producing antibodies and fighting infections. CLL is the most common leukaemia making up a quarter of leukaemia cases among adults, and NHL accounts for 4% of all cancers in the United States.

Source: Ohio State University

The Urgent Need for Early Detection Emphasised this Bone Marrow & Leukaemia Awareness Month

Credit: National Cancer Institute

Leukaemia has been identified as the most prevalent cancer among the country’s youth, according to the latest report from the National Cancer Registry (NCR) of South Africa (2021). However, approximately half of children with cancer remain undiagnosed, with the majority of cases only being detected during the advanced stages of the illness. This is partly attributed to a lack of awareness of the early warning signs of childhood cancer.

As the world observes Bone Marrow & Leukaemia Awareness Month until the 15th of October, Dr Candice Hendricks, Paediatric Haematologist and Medical Spokesperson for DKMS Africa shares that leukaemia can be categorised as acute leukaemias or chronic leukaemias, each with varying symptoms. “Acute leukaemias are far more common in children and can further be divided into acute lymphoblastic- (ALL) and acute myeloid leukaemia (AML). Among children, especially those aged between two and 10, Acute Lymphoblastic Leukaemia (ALL) is the most common blood cancer in this age group.

“This disease arises from genetic mutations in immature lymphocytes called lymphoblasts which are located in the bone marrow. The mutations lead to uncontrolled growth of these lymphoblasts,” she explains. “Lymphoblasts are abnormal blood stem cells that lose the ability to make mature blood cells. The uncontrolled growth of these cells in the bone marrow displaces normal blood cell development and leads to a decrease in properly functioning red blood cells, white blood cells, and platelets. Patients may potentially present with an elevated white blood cell count on blood results, however, their impaired function leaves the body vulnerable to infections.”

Aligned with the NCR, Dr Hendricks emphasises that early symptoms often go unnoticed, as they mimic common, mild conditions, causing many patients and those who care for them to overlook them. “However, the severity of these symptoms escalates rapidly with acute leukaemias and persist even after standard treatment for infections. A high index of suspicion is required in diagnosing patients, and if any symptom persists, an immediate full blood count test is necessary, followed by additional tests if irregularities are detected.”

Prominent symptoms indicating the disease include:

  • Blood clotting disorders or blood diathesis characterised by easy bruising from minor impacts and the appearance of small reddish spots on the skin. Other signs encompass blood in urine, as well as uncontrollable gum and nose bleeding.
  • Muscle and joint pain, particularly in the limbs, along with frequent limb numbness.
  • Fever and night sweats.
  • Anaemia caused by a deficiency of red blood cells, leading to constant fatigue, reduced exercise capacity, lethargy, sleepiness, and pale skin.
  • Recurrent infections that persist despite antibiotic treatment due to cancer cells impairing the immune system. Pathological cancer cells displace healthy leukocytes, rendering the body susceptible to various viral, bacterial, and fungal infections.
  • Loss of appetite and weight loss.
  • Enlarged lymph nodes.
  • Stomach pain resulting from spleen and/or liver enlargement.

In support of Bone Marrow & Leukaemia Awareness Month, DKMS Africa continues to raise awareness and funds to cover the registration costs for as many potential stem cell donors as possible. Stem cell donations offer the best chance of survival for children afflicted by high-risk leukaemia which does not respond to or recurs after standard treatment. Answer the call! If you’re aged between 17 and 55 and in good general health, please register at https://www.dkms-africa.org/register-now. Registration is entirely free and takes less than five minutes.

For further information, get in touch with DKMS Africa at 0800 12 10 82.

About DKMS
DKMS is an international non-profit organisation dedicated to saving the lives of patients with blood cancer and blood disorders. Founded in Germany in 1991 by Dr. Peter Harf, DKMS and organisations of over 1,000 employees have since relentlessly pursued the aim of giving as many patients as possible a second chance at life. With over 11 million registered donors, DKMS has succeeded in doing this 100,000 times to date by providing blood stem cell donations to those in need. This accomplishment has led to DKMS becoming the global leader in the facilitation of unrelated blood stem cell transplants. The organisation has offices in Germany, the US, Poland, the UK, Chile and South Africa. In India, DKMS has founded the joint venture DKMS-BMST together with the Bangalore Medical Services Trust. International expansion and collaboration are key to helping patients worldwide because, like the organisation itself, blood cancer knows no borders.

DKMS is also heavily involved in the fields of medicine and science, with its own research unit focused on continually improving the survival and recovery rate of patients. In its high-performance laboratory, the DKMS Life Science Lab, the organisation sets worldwide standards in the typing of potential blood stem cell donors.

Extended Chemotherapy Slashes Childhood Leukaemia Recurrence

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

Living Near Fracking Sites Increases Childhood Leukaemia Risk

Photo by Worksite Ltd on Unsplash

Children living near unconventional oil and gas (UOG) or ‘fracking’ developments at birth had a 2–3 times greater risk of leukaemia diagnoses between 2 and 7 years old, researchers have found.

Their study, published in the journal Environmental Health Perspectives, included nearly 2500 Pennsylvania children, 405 of whom were diagnosed with acute lymphoblastic leukaemia (ALL).

ALL arises from mutations to lymphoid immune cells. Although long-term survival rates are high, survivors may have long-term health risks and psychological issues. Unconventional oil and gas development, more commonly referred to as fracking (short for hydraulic fracturing), is a method for extracting gas and oil from shale rock. The process involves high-pressure injection of water, sand, and chemicals into bedrock to release oil or gas for extraction.

For communities living nearby, UOG development can pose a number of potential threats. As well as air pollution from vehicles and construction, there is also water pollution from hydraulic fracturing or spills of wastewater. Hundreds of chemicals have been reportedly used in UOG injection water or detected in wastewater, some of which are known or suspected carcinogens. The lack of data about this has given rise to concerns over the proximity of UOG to residential areas.

“Unconventional oil and gas development can both use and release chemicals that have been linked to cancer, so the potential for children living near UOG to be exposed to these chemical carcinogens is a major public health concern,” said the study’s senior author, Nicole Deziel, associate professor of epidemiology at the Yale School of Public Health.

“Studies of UOG exposure and cancer are extremely few in number. We set out to conduct a high-quality study to further investigate this potential relationship,” added Cassandra Clark, the study’s first author and a postdoctoral associate at the Yale Cancer Center. “Our results indicate that exposure to UOG may be an important risk factor for ALL, particularly for children exposed in utero.”

Oil and gas-related chemicals exposure could be through drinking water, the researchers found. The watershed, the zone from which a drinking water well serving their home would likely draw water, were compared with the distance from the home to the nearest of those UOG wells. UOG wells falling within the watershed area are expected to be more likely to impact the home’s drinking water supply, they said.

This work adds to a growing body of literature on UOG exposure and children’s health used to inform policy, such as setback distances (the required minimum distance between a private residence or other sensitive location and a UOG well). Current setback distances are the subject of much debate in the United States, with some calling for setback distances to be lengthened to more than 305m and as far as 1000m. The allowable setback in Pennsylvania, where the study was conducted, is 152m.

“Our findings of increased risk of ALL at distances of two kilometres or more from UOG operations, in conjunction with evidence from numerous other studies, suggest that existing setback distances, which may be as little as 150 feet (50m), are insufficiently protective of children’s health,” Clark said. “We hope that studies like ours are taken into account in the ongoing policy discussion around UOG setback distances.”

Source: Yale University