Blood vs Bone marrow: New technologies can reduce the need for bone marrow biopsies

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Bone Marrow Biopsies: a less painful alternative for routine check-ups

Until now, bone marrow sampling has been the primary technique for routine follow-up checks on MDS patients after initial diagnosis. The bone marrow is the heart of the disease and reveals important clues, for example, about whether a patient is responding to therapy or whether the disease is stable or worsening (progression).

During the procedure, which can be uncomfortable, an aspiration from the patient's marrow is taken, and specific blood cells derived from the bone marrow are analysed, allowing clinicians to monitor the ongoing disease status of a patient.

More specifically, clinicians may look for the presence of particular genetic mutations within the cells, what the DNA chromosomes physically looks like (a technique broadly called cytogenetics) and the shape of certain bone marrow blood cells (morphology).

However, although necessary, bone marrow biopsies have many downsides. Most notably the stress and physical discomfort to the patient, for which some patients require sedation. It is an invasive procedure which therefore always carries a risk of infection. This risk also increases in elderly patients, or those with a low or very low neutrophil (white blood cell) count. This makes frequent sampling problematic which means patients may not be followed as closely as clinicians would like. Overall, for many patients, regular biopsies are yet another 'painful' and inconvenient aspect of living with MDS.

Peripheral Blood Sample: An alternative to biopsy

 

An easier alternative to a biopsy would be a peripheral blood (PB) sample (i.e. the blood already circulating in the body, which is produced in the bone marrow).

Until recently, it had not been conclusively shown in a large scale study that PB could be used to obtain similar results as a bone marrow biopsy. Also, the commonly used testing technique, called metaphase cytogenetics, does not work very well for PB samples. Therefore until now, there has been little momentum in adopting a PB sampling as standard practice.

However recent research by a group at Kings College London and the Hospital may change that (A M Mohamedali et al). Their research has demonstrated that peripheral blood samples are an equally accurate and reliable source for monitoring the genetic mutations in bone marrow derived blood cells, and hence for monitoring the disease status of a patient (please see below for full publication details).

The research group looked for the presence of various genetic abnormalities known to be frequently associated with MDS in both bone marrow samples and PB samples, and compared the results against each other.

In order to do this, they used two specific testing methods which do work for PB samples. The first is a technique called SNP – Array karyotyping (a method used to identify changes to the number of DNA strands in a cell, a feature commonly observed in MDS). The second technique used was next-generation sequencing technology (NGS) to look at over 20 genes known to harbour mutations in up to 80% of MDS patients. They found that if a gene mutation or changes to the number of DNA strands could be detected in a bone marrow biopsy sample, it could also be detected in the PB sample of the same patient. Overall, they found that the same results could be obtained for both bone marrow biopsy and PB samples using these techniques (there was a 98% concordance in results, which is extremely high).

These are very promising results which demonstrated proof of concept that PB can be used as a substitute for bone marrow biopsies. The authors of the publication recommend the use of PB for follow-up checks and believe that PB sampling has many distinct benefits over bone marrow sampling.

The most obvious being the fact that the method is less invasive and virtually pain free, with little or no risk of infection. This allows for more frequent check-ups which in turn enables closer disease monitoring for better outcomes. The procedure is also quicker and easier to perform than a biopsy, and as no sedation is required, patients are also able to leave immediately with no recovery time required.

Aside from patient benefits there are also important advantages for hospitals too. The procedure is easier and quicker to carry out than a bone marrow biopsy, therefore does not require specialist staff and cuts down on procedure time. In some cases it may even free up hospital bed time and offer cost savings.

Additionally, once the PB sample is taken, it can be analysed relatively easily using the two testing techniques described by the research group. Both the SNP – Array karyotyping and 21st century sequencing techniques were semi-automated, reliable and provided robust results, making it attractive for hospital diagnostic labs to implement.

Although a bone marrow biopsy will always be essential for initial diagnosis, finding easier, less painful, yet still accurate and reliable ways to monitor MDS patients represents a major improvement. PB sampling could spare a large population of patients the need for repeat bone marrow biopsies, making the burden of their disease a little lighter, and allowing clinicians to follow patients more closely through more regular checks.

MDS UK – Note to patients

If you are not yet offered the choice of peripheral blood (PB) sampling during routine check-ups and would like more information about its use, please contact MDS UK. This is a fairly recent technology, therefore if your haematologist has not yet started using it please hand a copy of this article to him/her. We would be happy to provide more information directly to you and/or your haematology consultant.

MDS UK – Note to haematologists

Further details about this technology can be found via: Research paper in Leukemia.

Please quote the following information if you wish to use our ResearchFORPatients article:

Source: www.mdspatientsupport.org.uk / ResearchFORpatients
Author: MDSUK/Stephanie Brett email: mds-uk@mds-foundation.org twitter: @mds_uk

Original reference paper:
A M Mohamedali, J Gaken, M Ahmed, F Malik, A E Smith, SBest, S Mian, T Gaymes, R Ireland, A G Kulasekararaj, G J Mufti, High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS)
Leukemia. 2015 Sep;29(9):1928-38

Clinician and Researchers Quotes

This research has provided us with the very important information that the genetic abnormalities found in the bone marrow of MDS patients are also detected in the blood. We already know that many patients acquire new genetic abnormalities during disease progression and it would therefore be possible to monitor for this on a blood sample. At present the main limiting factors for adopting this approach are the cost of these technologies as well as the complexity of analysing the data produced. The price will however fall over time and we will continue to simplify the data analysis process meaning that this has real potential for the future management of MDS patients. Unfortunately I don’t think this will replace the need for a bone marrow biopsy as this remains critical in confirming disease progression however it may allow us to detect changes early and determine when this procedure should be performed. Further research will be needed to find out if this can improve the overall management and outcome in MDS patients.

Dr Catherine Cargo, Consultant in Clinical Haematology, Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals NHS Trust

From a clinical perspective, this study is the first of its kind to demonstrate the potential use of 21st century technologies in improving the management and treatment of human diseases, especially in a disease like MDS where the majority of the patients are of old age (> 70 years). This study has clearly shown that the genetic analysis that is usually performed on bone marrow biopsy can also be reliably done on peripheral blood, thus potentially eliminating the need for repeated painful and expensive bone marrow aspirations for disease monitoring. That being said, further larger studies involving multiple centres are needed to verify these results before being introduced into routine clinical practice. Although there are challenges that need to be addressed including the cost and the data management as well as interpretation of the results, however, this technological advancement has great potential for the clinical management of MDS patients and will also help in early intervention where disease progression is suspected.

Syed Mian, PhD, Research Associate (one of the authors of this research paper) Department of Haemato-Oncology, King’s College London

Currently only a handful of specialist laboratories are equipped to perform SNP-Array karyotyping or next generation sequencing mutation analysis in MDS. The number of centres tends to be small because these types of analysis are highly specialised, require the use of expensive, dedicated equipment and require highly skilled and experienced staff. These laboratories tend to be within specialised Haematological Malignancy Diagnostic Centers such as the service in Leeds Teaching Hospitals NHS Trust and my laboratory within King’s College Hospital London. The cost of these investigations is relatively high, however the amount of genetic information obtained using these methods is much greater and results in improved certainty of diagnosis. Some of these genetic findings are also useful for informing clinicians and patients about the likely course of the disease and can also influence treatment options in a way that the conventional methods may not. Here at King’s College Hospital we have been performing this next generation sequencing mutation analysis and SNP-array karyotyping in MDS for several years. We have performed analysis on hundreds of samples and these analyses are now available as diagnostic tests. Access to these analyses make replacement of some bone marrow biopsy samples with blood a reality for our patients.

Nicholas Lea, PhD, Clinical Scientist, Laboratory for Molecular Haemato-Oncology, Department of Haematology, King’s College Hospital London

Our study was designed primarily with the patient benefit in mind. Being a tertiary referral centre for MDS, there was a clear need to improve on existing methods in aiding patient diagnosis and enable frequent follow up of patients. The data is an extension of our earlier publication in the journal Blood (2013) and confirms the very high concordance of the genetic information obtained from the bone marrow and peripheral blood. I am delighted that MDS UK has taken the initiative to disseminate this information to the community so that patients may benefit from cutting edge research tools to help and with their MDS journey

Dr Azim M Mohamedali, PhD Senior Research Fellow, Department of Haemato-Oncology, King’s College London


Survey in Europe – Measuring Quality of Life

London School of Economics Survey about how quality of life is measured and reported in Health Technology Assessments (HTA)

28/05/15

Another survey for patients and carers to take part.

HTA organisations, such as for example NICE (National Institute for Clinical Health and Excellence) mostly use a questionnaire called the EQ-5D to measure the impact of an illness.  From our experience with MDS patients, we have found this EQ-5D questionnaire inadequate to reflect the various issues faced by our group of patients.  This survey is an opportunity to test and evaluate this widely used questionnaire.
We therefore welcome this survey and project – and encourage you to take part – both patients and caregivers/carers.
Thank you.

Here is the official invitation, background and links to the survey:

The London School of Economics (LSE) is leading an EU-funded research project, Advance-HTA, looking at aspects of health technology assessment (a method used to determine where and how new treatments should be introduced into a national healthcare system). The goal is to work with a range of stakeholders to explore how the methods used in HTA can be improved to better meet the needs of both patients and modern healthcare systems.  There are 13 institutions involved in the research from a number of EU countries and North America.

One area of particular interest is the way in which patients’ experience in quality of life is measured.  Currently, a tool called EQ-5D-5L is used but there is considerable discussion about how well this reflects the aspects of health-related quality of life that matter to people living with an illness.

We are asking patients with a range of illnesses, from a number of countries, to complete a short questionnaire aimed at finding out ‘Does EQ-5D-5L accurately and reliably reflect the aspects of their health that matter most to patients?’.  This is important because it will help ensure that the things that matter to patients are at the heart of future decisions about access to medicines.

FOR PATIENTS
The questionnaire will take approximately 5minutes to complete and can be found at the following link:
https://lse.qualtrics.com/SE/?SID=SV_abftZRBx9Sj4N1P  

FOR CAREGIVERS
Another version of the questionnaire has been developed to capture the responses of the caregivers who are providing support and care for patients. If you know any family members and friends who are caring for a patient, please provide them with the following link to complete the questionnaire: https://lse.qualtrics.com/SE/?SID=SV_9sM3VwpFLDT1xVH

Each questionnaire must be completed in one sitting and all responses are anonymous.

If you are involved in a patient organisation, please consider posting the links to the surveys on your organisation’s website.  If you know other patient organisations in Europe, please do forward them the links. The more completed questionnaires we receive, the more reliable the results will be.

Thank you very much for taking the time to complete the questionnaire and support this important piece of research.  More information about the project and the institutions involved can be found at http://www.advance-hta.eu.

Kind regards,

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Russell’s stem cell transplant experience – new video

New video clip – Russell Cook’s stem cell transplant experience
05/03/15

We have uploaded a new video clip of our friend and new MDS UK trustee Russell Cook.

He tells us in detail about his experience of his three stem cell transplants – two from an unrelated donor – which failed, followed by stem cells from his 15 year old son Luke – which fortunately did work.

Russell has since gone on to run several marathons – and is doing extremely well.

Russell’s Stem Cell transplant from mds patient support on Vimeo.

 

A stem cell transplant is not an easy treatment option – nor is the decision to opt for a transplant.
If you are considering a stem cell transplant, please do have numerous conversations with your transplant team – until you have all the information you feel you need to make the decision.

Check the Anthony Nolan website, read the booklet “The 7 steps”.
All to be found on our Information Material webpage.

You may also talk to other patients – but do remember that every patient experience is fairly unique.
We have several other pages on our website that may help you as well.

Check our Useful links page – listing several stem cell transplant blogs – including practical tips on what to bring to hospital – how to cope for those 2-4 weeks in isolation, whilst the stem cells engraft.

If you are a healthy individual – aged 16 to 55 – please do consider registering to become a stem cell donor.
Your contribution and potential donation will save lives.
Contact Anthony Nolan or Delete Blood Cancer – visit our bone marrow donation page to learn more: Stem Cell Marrow Donation

You may also want to watch this great clip from our colleagues at the ACLT:

 


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