Quality of Life is an Important Treatment Goal in Patients with MDS

Researchers designed an antibody that recognises and destroys CD99-covered leukemia cells while sparing normal blood stem cells

This is a microscopic image of a leukemia cancer stem cell (Credit: Montreh Tavakkoli) with normal DNA coloured in blue. CD99, those green-coloured spots, is a protein-sugar molecule, which occurs more frequently than normal on stem cells responsible for blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Building on this discovery, researchers from NYU Langone Medical Center and Memorial Sloan Kettering Cancer Center designed an antibody that recognises and destroys CD99-covered leukemia cells while sparing normal blood stem cells, a finding confirmed by experiments in human cells and in mice with AML cells.

Antibodies are immune system proteins that stick to a specific target. In recent years, researchers have become capable of engineering antibodies so that they target disease-related molecules.

"Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells," says corresponding study author, Christopher Y. Park, MD, PhD, associate professor in the Department of Pathology at NYU Langone and its Perlmutter Cancer Center.

"While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing," says Park.

Direct Cell Killing

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from abnormal stem cells that build up in bone marrow until they interfere with normal blood cell production. Patients struggle with anemia, increased risk for infection, and bleeding.

In AML, a small group of leukemic stem cells become incapable of maturing into red or white blood cells as intended. Most leukemias respond initially to standard treatment, but relapse is common as standard treatments fail to kill leukemia stem cells, which continue to multiply.

The researchers examined stem cells from 79 AML and 24 MDS patients and they found that approximately 85% of stem cells in both groups had high levels of CD99. The levels were so high that diseased stem cells could be cleanly separated from related, normal stem cells in AML patients.

The research team then made several CD99 antibodies, and chose to focus on the one that most effectively killed those cells. Researchers found that when the study antibody attaches itself to CD99 on the surface of a cancer stem cell, it causes leukemia stem cells to die.

"With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials," says Park.

More information: "CD99 is a therapeutic target on disease stem cells in myeloid malignancies," Science Translational Medicine stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaj2025

Provided by: New York University School of Medicine

Evidence tells us that when patients are actively involved in their own care, treatment and support can improve outcomes and experience for patients.

Everyone involved in care should advocate for the experience, voice and presence of patients, carers and the public to make a real difference to research in the NHS in order to improve health and well-being.

We all know importance of maintaining a healthy lifestyle through exercise and a healthy diet, but what else can be done?

Help and get actively involved in the work of the NIHR, the National Institute for Health and Research

In their website you'll find out about research that has taken place, you can take part in a free online course and contribute with questions and ideas for research.

The National Health Service (NHS) states:

The NHS is there to improve our health and wellbeing, supporting us to keep mentally and physically well, to get better when we are ill and, when we cannot fully recover, to stay as well as we can to the end of our lives. It works at the limits of science – bringing the highest levels of human knowledge and skill to save lives and improve health. It touches our lives at times of basic human need, when care and compassion are what matter most.

The NHS is founded on a common set of principles and values that bind together the communities and people it serves – patients and public – and the staff who work for it.

The Constitution Handbook adds:

Research is a core part of the NHS. Research enables the NHS to improve the current and future health of the people it serves. The NHS will do all it can to ensure that patients, from every part of England, are made aware of research that is of particular relevance to them.

Going the Extra Mile

The NIHR in England in their Going the Extra Mile report provides the strategic vision and direction for our work in engaging and actively involving patients, carers and the public in all aspects of research. It sets the following goals:

By 2025 we expect all people using health and social care, and increasing numbers of the public, to be aware of and choosing to contribute to research by:
- Identifying future research priorities and research questions
- Informing the design and development of innovations
- Participating in research studies
- Advocating for the adoption and implementation of research in the NHS

Both health workers and patients should ensure that they contribute to INVOLVE and ensure that information held on their website about where they work or receive care is accurate.

What's happening elsewhere?

We do need to consider what is happening elsewhere by exploring, for example: the European Patients‘ Academy on Therapeutic Innovation (EUPATI), the Irish Platform for Patient Organisations, Science and industry (IPPOSI). Further afield there is the Canadian Institutes for Health Research and their Strategy for Patient Orientated Research. You may also choose to look at the developments of Involving People in Research in Western Australia and the Patient Centred Outcomes Research Institute (PCORI) in the USA. These cover many of the leading economies and we risk deepening the health inequalities unless we also look at what is happening in there countries.

The great work of charities

There are many charities who focus on health research and others who carry out research themselves. Many are now actively involving patients and the public in the research that they fund. This ranges from priority setting, improving study design and sitting on funding decision making panels.

The Shared Learning Group on Involvement brings together a number of people working in charities doing patient, public involvement and engagement. They also have a ‘research sub-group’. Parkinson's recently produced an excellent guide for their researchers on patient and public involvement. The Association of Medical Research Charities (AMRC) is a further good source of information.

The role of Universities

There is a significant amount of public involvement taking place across all academic institutions. This is partly driven by the Research Excellence Framework which requires research work to have ‘reach’ and ‘significance’. It is worth finding out about the Academic Health Sciences Network (AHSN) and the local Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

As of the 20th of October, the European Medicines Agency (EMA) gives open access to clinical reports for new medicines authorised in the European Union.
For every new medicine, citizens, including researchers and academics, will be able to directly access thousands of pages from clinical reports submitted by pharmaceutical companies. Clinical reports give information on the methods used and results of clinical trials conducted on medicines.
Vytenis Andriukaitis, European Commissioner for Health and Food Safety, said

"Transparency is an essential component in clinical research. Its outcome – whether positive or negative – should be made publicly available."

With EMA’s proactive approach to providing access to the data, patients and healthcare professionals will be able to find out more information about the data underpinning the approval of medicines they are taking or prescribing.

It will also facilitate the independent re-analysis of data by academics and researchers after a medicine has been approved. This will increase scientific knowledge, and potentially further inform regulatory decision making in the future.

Increased transparency will also benefit innovation. The shared knowledge about a medicine helps developers learn from the experience of others and can lead to more efficient medicine development programmes by reducing duplication of research and de-risking some new developments.

This will be a learning curve for the Agency and all its stakeholders, as they start to apply the policy for the first time.

While the policy gives an unprecedented proactive access to clinical data, it also demands the highest standard of protection of patients’ personal data. The process will evolve over time as more experience is gained and may lead to adaptations of EMA’s guidance.

Leukaemia Care is asking patients to fill in a new questionnaire about their care and treatment for blood cancer. Its purpose is to provide information, which will help the NHS and Leukaemia CARE to monitor and improve the quality of health services for future patients with blood cancer.

Leukaemia CARE is interested in finding out more about your experience of treatment for blood cancer, in order to ensure that the services provided meet patient needs and to help focus campaigning efforts on areas where NHS care for blood cancer could be improved.

Taking part in this survey is voluntary. Published reports will not contain any personal details.

Who should complete the questionnaire?

The questions should be answered by you, as the person who has been treated for a blood cancer. If you need help to complete the questionnaire, the answers should be given from your point of view – not the point of view of the person who is helping.

If you have any queries about the questionnaire, please call the FREEPHONE helpline number on 0800 783 1775

Please complete the questionnaire and return it in the FREEPOST envelope. No stamp is needed. The questionnaire should take around 20 minutes to complete.

Or if you prefer you can complete the questionnaire online at: www.myonlinesurvey.co.uk/LE16ANON

Who is organising the survey?
The survey is being carried out by an experienced health research company, Quality Health, on behalf of Leukaemia CARE, who will produce public reports which will include the anonymous survey findings. These reports will be available to view on the Leukaemia CARE website in early 2017.

At no point will your name and address be linked to your responses for this survey. Your responses will only be used to provide information about the quality of services that blood cancer patients have experienced.

Need further information?

If you would like more information about the survey, protection of your data, or have questions on how to complete the questionnaire, you can call:
Quality Health’s FREEPHONE helpline on 0800 783 1775
The line is open between 9am and 5pm, Monday to Friday and there is an answerphone at all other times where you can leave a message.

Fresher is not better

It's been long thought that when blood transfusions are needed, it may be best to use the freshest blood, but McMaster University researchers have led a large international study proving that it is not so.

The study of almost 31,500 patients at six hospitals in four countries showed that having a transfusion with the freshest blood did not reduce the proportion of patients who died in hospital. The McMaster study was published in the New England Journal of Medicine.

"It's been a contentious issue, but our study finally puts an end to the question about whether stored blood could be harmful and fresher blood would be better," said Nancy Heddle, lead author and a professor emeritus of medicine for McMaster's Michael G. DeGroote School of Medicine. She is also the research director of the McMaster Centre for Transfusion Research.

"Our study provides strong evidence that transfusion of fresh blood does not improve patient outcomes, and this should reassure clinicians that fresher is not better."

She added that the results are also good news for blood suppliers worldwide as having a supply of stored blood helps to ensure that blood is available when a patient needs it.

The 31,497 adult patients studied were at hospitals in Australia, Canada, Israel and the U.S. The mortality rate was 9.1 per cent with people receiving the freshest blood, and 8.7 per cent among those receiving the oldest blood. There was no significant difference when looking at the patients' blood type, diagnosis, hospital or country.

Blood can now be stored up to 42 days before transfusion

John Eikelboom, a co-principal investigator of the study and professor of medicine of the Michael G. DeGroote School of Medicine, said more than 40 studies published earlier have failed to adequately answer the question about whether the freshest blood was best.

"Blood transfusions are a common medical intervention," he said. "Advances in blood storage now allow blood to be stored up to 42 days before transfusion and the usual practice is to use up the blood that has been in storage the longest. But, because there are biochemical, structural and functional changes in the blood during storage, there had been concerns about the use of 'older' blood.

"This study reassures us that aging is not bad - even for blood."

The study was funded by the Canadian Institutes of Health Research, Canadian Blood Services and Health Canada.

Article: Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion, Nancy M. Heddle, M.Sc., et al., New England Journal of Medicine, doi: 10.1056/NEJMoa1609014, published 24 October 2016.