Tag: leukaemia

Categories : CancerTags :

Research Identifies Beneficial Genetic Changes in Regular Blood Donors

On By ModernMedia
Photo by Charliehelen Robinson on Pexels

Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells.

Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukaemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.

Blood donation impacts makeup of cell populations

In research published in Blood, the team at the Crick, in collaboration with scientists from the DKFZ in Heidelberg and the German Red Cross Blood Donation Centre, analysed blood samples taken from over 200 frequent donors – (three donations a year over 40 years, more than 120 times in total) – and sporadic control donors who had donated blood less than five times in total.

Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.

For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukaemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukaemic.

A balancing act

To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukaemia and also the non-preleukaemic changes observed in the frequent donor group.

They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.

The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukaemic.

This suggests that the DNMT3A mutations observed in the frequent donors are mainly responding to the physiological blood loss associated with blood donation.

Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.

The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukaemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.

The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukaemic mutations associated with blood cancer.

Interactions of genes and the environment

Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick, and senior author, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favours mutations that further promote stem cell growth rather than disease.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukaemic mutations and we will need to look at these results in much larger numbers of people. It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”

Hector Huerga Encabo, postdoctoral fellow in the Haematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the DKFZ in Heidelberg, said: “We know more about preleukaemic mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically.”

Source: The Francis Crick Institute

Categories : CancerTags :

The Truth About Bone Marrow Stem Cell Donation

On By ModernMedia
SAG Leukaemia. Credit: Scientific Animations CC0

While thousands of South Africans have registered as potential bone marrow stem cell donors, a critical challenge looms: donor attrition. These dropout rates, ranging from 23% to 56%, can significantly delay finding a suitable match for blood cancer patients in desperate need of a potentially life-saving transplant. This can unfortunately impact their chances of survival.

The good news is that donating stem cells is a safe and relatively simple process. With Bone Marrow Stem Cell Donation and Leukaemia Awareness Month taking place between 15 August and 15 October 2024, DKMS Africa aims to address some misconceptions that might deter registered donors from following through with donations.

Palesa Mokomele, Head of Community Engagement and Communications, unpacks these below:

Myth 1: Donating stem cells is a painful surgical procedure.

Fact: For over 90% of donors the process entails Peripheral Blood Stem Cell (PBSC) collection, a non-surgical procedure similar to donating blood. During PBSC, donors will rest comfortably while a needle is placed in each arm. Blood is drawn from one arm, passed through a machine that separates the stem cells, and the remaining blood is returned to the body through the other arm. While not painful, some donors may experience mild side effects like headaches, fatigue, or muscle aches, which typically resolve quickly.

For a small percentage of donors (around 2%), stem cells might be collected directly from the bone marrow in the pelvic bone. This minimally invasive procedure is performed under general anaesthesia. Although some donors experience temporary discomfort or soreness at the extraction site, the feeling is usually comparable to a bruise.

Myth 2: Donating takes too long and disrupts my life too much.

Fact: While the donation process involves some steps, it’s designed to be manageable. You’ll likely have a briefing call to explain the process, a health check to confirm your suitability, and an informative session about donation itself. The actual donation typically takes less than a day (4-6 hours) for the PBSC method.

For the bone marrow donation method, a hospital stay is involved, but it’s usually just three days. This includes check-in on day one, the procedure on day two, and discharge on day three.

Myth 3: Donating stem cells means missing a lot of work. 

Fact: The good news is that most donors can get back to work quickly. For PBSC donation, donors will likely be able to return within two days. If they donate bone marrow, a bit more recovery time is needed, so they should plan for about one week of leave.

Myth 4: My boss won’t be okay with me taking time off to donate.

Many employers are incredibly supportive of staff who donate stem cells. In our experience, most react positively to this selfless act. If your company doesn’t offer paid leave for donation, DKMS has a financial assistance programme that deals with lost wage compensation.

Myth 5: Donating stem cells will cost me money.

Fact: Donation is completely free of charge for the donor. DKMS covers all donation-related expenses, including travel, meals, and accommodation if needed. Financial support is also provided for a companion to join them at the hospital. The donor’s health insurance will never be involved, and DKMS handles the costs of any follow-up care that might be necessary.

“Seventeen-year-old Anele who was diagnosed with Acute Lymphoblastic Leukaemia (ALL), a type of cancer that affects the production of healthy blood cells, is just one of many patients in need of a stem cell transplant from a matching donor,” says Mokomele. “His father, Lawrence, is devastated, with his son now hanging on for dear life, waiting for that one person to be a match.”

“Every registered donor brings hope to a patient battling blood cancer. By staying committed to the cause, you help to ensure a readily available pool of potential matches, increasing a patient’s chance of receiving a transplant. Let’s give them a second chance at life!” she concludes.

Register today at https://www.dkms-africa.org/register-now

For more information, contact DKMS Africa on 0800 12 10 82.

Categories : CancerTags :

Cell Donor’s Socioeconomic Status Affects Cancer Treatment Outcomes

On By ModernMedia
SAG Leukaemia. Credit: Scientific Animations CC0

In a study published in the journal PNAS, a research team led by the University of Minnesota Medical School have shown that the socioeconomic status (SES) of cell donors affects the health outcomes of blood cancer patients who underwent haematopoietic cell transplantation (HCT). 

The study examined the health outcomes of 2005 blood cancer patients treated with HCT in the United States. The research team found cancer patients who were transplanted with cells from donors of greatest socioeconomic disadvantage experienced a 9.7% reduction in overall survival and 6.6% increase in transplant-related mortality at three years compared to those transplanted from donors of high socioeconomic status – regardless of the cancer patient’s socioeconomic status.

“Our findings are quite remarkable. We have shown that social disadvantage penetrates so deeply that it is actually transplantable into a new host, and its effects persist over time,” said Lucie Turcotte, MD, MPH, MS, an associate professor at the University of Minnesota Medical School.

The results show the striking biological impact of social disadvantage and how it can alter health outcomes, specifically in the setting of cancer and hematopoietic cell transplantation. 

The research team plans to conduct further research to investigate the underlying biological and physiologic drivers of these findings in order to develop interventions to mitigate the adverse health outcomes introduced by socioeconomic disadvantage. 

“The importance of these findings reach far beyond cancer and bone marrow transplant care – they demonstrate the profound health effects of social inequality and highlight the critical need for public health interventions,” said Dr Turcotte. 

Source: University of Minnesota Medical School

Categories : CancerTags :

Promising Drug Combination for Multiple Myeloma Treatment

On By ModernMedia
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

Categories : Cancer Cardiovascular DiseaseTags :

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

On By ModernMedia
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

Categories : Cancer PaediatricsTags :

Conquering Childhood Leukaemia: How You can Help

On By ModernMedia
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.

Categories : CancerTags :

Resounding Success for New Personalised Treatment for Adult Leukaemia

On By ModernMedia
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

Categories : Cancer GeneticsTags :

CRISPR-Cas9 Gene Editing may Unleash Cancer Cell Resistance

On By ModernMedia
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

Categories : CancerTags :

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

On By ModernMedia
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:

Categories : Cancer New Compounds and TreatmentsTags :

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

On By ModernMedia
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