Managing myelodysplastic syndromes (MDS) – from diagnosis to treatment 

Myelodysplastic syndrome (MDS), or myelodysplasia, is a blood disorder that causes a drop in your number of healthy blood cells. MDS covers a spectrum of disorders from indolent (slow developing) to aggressive (that rapidly develop or change into leukaemia).

MDS can affect people of any age, but is most common in people over the age of 65. Only one in five people with MDS are younger than 50. For most people, symptoms are mild at first and slowly get worse. Sometimes you may even have no symptoms at all, but have had a blood test that shows there is a problem. The treatment of MDS is constantly evolving and new drugs are being tested all the time.

Our expert is consultant haematologist Dr Beth Payne who specialises in treating patients with myelodysplastic syndromes and bone marrow failure. She is also a Senior Clinical Researcher funded by the Wellcome Trust and The Leuka John Goldman Fellowship for future Science and runs a research laboratory studying the mechanisms of disease in bone marrow failure and myelodysplastic syndromes and is also working to develop novel therapeutics.

Please read a transcript of the web chat below.

10:11 UCLH: 
Good morning and welcome to our web chat. We will begin at 12:00 noon, but you can submit your questions now in preparation for the chat. Please note: your questions will not appear in the main chat window until after 12:00 noon.

Dr Beth Payne will be joining us to take your questions on ‘Managing myelodysplastic syndromes (MDS) – from diagnosis to treatment’ and will try to answer as many questions as possible within the hour long web chat.
11:59 Dr Beth Payne: 
Hello, I am Dr Payne, Haematology consultant here at UCLH ready to take your MDS questions
12:00 [Comment From Kevin: ] 
I was diagnosed with MDS late in 2013. I have been a runner for 35+ years and had been running ultra-distance races since the early 1980s. In 2012 as part of my training for the Comrades Marathon I took part in the 56 mile Glasgow to Edinburgh run. I took it steady and finished in good form. A couple of weeks later I came down with a quite severe chest / throat "man flu" type infections which curtailed my training for a couple of weeks. When I had recovered I tried to pick up the training again but found myself suffering from breathlessness and the rapid onset of fatigue most noticeable in my quadriceps - I was unable to run more than 4 or five miles without distress. My question is could the infection have somehow contributed to the onset of MDS, perhaps sped it up? (as an ultra-runner I am very familiar with fatigue, and recognised that the fatigue I was feeling was different to the fatigue I experienced in training and racing)
12:00 Dr Beth Payne: 
It is unlikely that the infection contributed to the onset of the MDS per se . It is not unusual however for infections to result in worsening of the symptoms of anaemia, or for infections to lead to the diagnosis of a blood disorder (like MDS). This is because the immune system may be compromised from reduced white blood cell counts. In the case of MDS we know that there are many genetic events over a long period of time that lead to the development of disease in most cases.
12:03 [Comment From Kevin: ] 
My question is about EPO - as I understand it people with MDS have a much greater production of blood cells a percentage of which are malformed and / or die young. If the effect of EPO is to boost cell production what is the mechanism for it to work, is there a difference in the type or ratio of cells produced with EPO?
12:04 Dr Beth Payne: 
Good question! Epo is a normal hormone that is designed to increase the number of red blood cells when they become reduced (for any reason – e.g. have a large bleed in a road traffic accident or having low levels of iron). Only some MDS patients respond to Epo. The MDS patients who respond to Epo are those patients who have an inappropriately low level of their own Epo in response to their anaemia. We don’t see any difference in the kind or ratio of red blood cells produced, Epo simply drives more production.
12:06 [Comment From MDS UK Patient Support Group: ] 
Which MDS trials do you think are most promising at the moment?
12:06 Dr Beth Payne: 
I think that it is really exciting to see new treatments targeting that immune system coming up. We have 2 studies opening shortly that will assess an antibody treatment targeting PD-L1 along with conventional treatment with azacitidine. PD-L1 inhibitors work by allowing the body to recognise abnormal MDS cells and kill them. This is exciting because it is not just so much the therapy that kills the cells but our own bodies. Our first study will be opening next week.
12:13 [Comment From Fearne: ] 
Why can some blood cells be dysplastic even after a SCT
12:13 Dr Beth Payne: 
It partly depends on how many of the cells are of donor origin and how many are recipient (ie residual MDS cells). After a transplant sometimes there is a mixture of patient and donor cells (we call this mixed chimerism) before the donor cells fully take over. You should chat to your haematologist if you think you might have mixed chimerism to see if anything needs to be done. If the cells are of donor origin, this can occur as a result of the chemotherapy that is given for the SCT.
12:15 [Comment From Guest: ] 
Ah ok, so if my EPO levels are normal then taking EPO would not necessarily boost my Hg levels, but if my EPO was low then it might well be beneficial?
12:15 Dr Beth Payne: 

If they are normal this would be “inappropriately low” if you are anaemic since normal response would be to have a high epo. Therefore a trial of epo would be of benefit if this is the case
12:19 [Comment From Donna: ] 
Hello, I was diagnosed with MDS RCMD, low risk, 18 months ago, I am now aged 40. I am just wondering what treatments may be available for my type in the near future? Thank you
12:19 Dr Beth Payne: 
As you are low risk we would usually just watch and wait to start with. However, given your age I think it would be appropriate to consider if you have a matched donor (sibling or unrelated) thinking about a transplant in the future. I also think that testing you for genetic markers that might give an indication of increased risk of progression over time would be of benefit with the caveat that these tests are mainly only available on a research basis at the present time. Of course other new treatments are being tested all the time and may become available before you require treatment
12:26 [Comment From Barbara: ] 
There has been much discussion in the MDS Patients Facebook group about lumbar biopsies. I have had 3 so far, my experience was not too bad compared with that of others. We appreciate that this procedure is vital for MDS patients. Can anything be done to make this procedure easier for the medical staff to perform and less painful for the patient?
12:26 Dr Beth Payne: 
I appreciate that bone marrow tests can be very painful. It is often operator dependent and we have found that training our nursing staff to perform them has really helped patient experiences. The key factors I find are ensuring enough time is given for anaesthetic to work. When you go to the dentist they send you out of the room for 10 minutes before they start because the effect is not immediate. It is the same with bone marrow. Adequate time is essential. We also use entonox (gas and air – like when you have a baby) here which works well. Unfortunately we are somewhat limited in the use of sedation now as most trust prohibit the use of sedation without the presence of an anaesthetist. Instead we use a pre-med about 30 mins before of lorazepam for those who need it.
12:30 [Comment From Dr.Moslemi: ] 
Dear Dr.Payne, My father in law is a 58 years old man known case of hypertension since 1 year ago (on medication and it's controlled) who was relatively well till about 7-8 months ago, The CBC was checked for him due to doing coronary angiography, CBC revealed all Hematologic categories are in lower limit of normal (WBC, RBC, Plt) with any work up. about 2-4 months later, he presented with 3-5 ecchymosis in different sites of his skin. CBC was checked for him, revealed pancytopenia. Then he underwent bone marror biopsy and lab data was checked for him with the impression of myelodysplastic syndrome!!! He has negative hx of weight loss, Night sweating , loss of appetite, Fatigue, Nose bleeding or GI Heeding Past medical Hx: Hypertension (on medication), coronary artery dx (Angiography note: ) and lung hypersensitivity Drug Hx: metoral 12,5mg qd losartan 50 mg qd Danazolbtab 100mg BID nitrocantin tab 6.4mg BID Prednisolon 7.5 mg BID Amilopress tab 5 mg QD Supplement (ca,folic acid, B12,...) Family Hx: parkinson in his sister, chronic bronchitis in his mother and father Social Hx: opium addict since 12 years ago, diet low fat,low salt Review of system: ecchymosis on his sternum and arm. No lymphadenopathy No organomegaly Is your diagnosis MDS or Not?
12:30 Dr Beth Payne: 
The findings in your fathers blood would be consistent with a diagnosis of MDS but it is impossible to say definitively without all test results and bone marrow examination. You should discuss the findings with his haematology consultant.
12:35 [Comment From Guest: ] 
It appears that my computer is uploading part messages so apologies for that. I take it that the studies are for a particular sub type of MDS?
12:35 Dr Beth Payne: 
Yes, the PD-L1 inhibitor studies are for patients who have RAEB2 or above. We have several ongoing studies for patients with this stage of disease including those who have failed azacitidine. We also have a study for low risk MDS patients. This looks at whether EPO treatment can be improved with the use of Exjade. Exjade is a drug used to treat iron overload (from blood transfusion) but in the early studies of this drug it was noticed that some of the patients getting Exjade for iron overload who also had MDS stopped requiring transfusions suggesting it might have activity against MDS on its own.
12:39 [Comment From Chris: ] 
Assuming a reasonably good state of health, apart from MDS, what is the maximum age for a Stem Cell Transplant?
12:40 Dr Beth Payne: 
This partly depends on whether you have an identical brother or sister (sibling) donor. Fit and well we would transplant up to 70 with a sibling donor, 65 with an unrelated donor. No hard and fast rules to this and you will find some variability between transplant units.
12:45 [Comment From Guest: ] 
Hi DR Payne I was diagnosed with RCMD in May 2015 I have low white blood cells and low neutrophils i suffer from severe mouth ulcers and have also been having severe pains in both my ankles just under the inside of the ankle bone, I also get other aches and pains in my joints can this be related to my condition. i AM ON Prophylatic anti biotics and mouth washes. Is the joint pain due to my condition? I am currently on watch and wait, what triggers further treatment.
12:46 Dr Beth Payne: 
Mouth ulcers (and sometimes other skin issues) are common with MDS (even without neutropenia). We sometimes see that these get better with growth factors (G-CSF) or steroid mouthwashes depending on their cause. The joint aches and pains are less easy to explain. They could be related to anaemia but I would probably also want to check for associated immune causes since MDS can have other immune conditions associated with it that might explain these symptoms. The best thing is to chat to your consultant about possible options. Usually treatment is triggered by symptoms or an increase in the number of primitive blood cells in the bone marrow.
12:46 [Comment From MDS UK Patient Support Group: ] 
For follow-up biopsies, there is now a new - and very recent way to use peripheral blood to check on results - instead of doing biopsies. We will shortly publish a patient friendly article on this topic - together with the clinical reference paper this technique is based on. Early days - but hopefully promising results.
12:48 Dr Beth Payne: 
Thanks - thanks for that comment. We also use molecular testing on to follow patients using blood rather than marrow. Sometimes we still need to do the bone marrow but i agree looking forward hopefully much less.
12:52 [Comment From Robert: ] 
Do you use lenalidomide on non-del5q MDS patients? I was diagnosed with RCMD MDS 8 years ago. Though low-risk, I needed treatment from the outset--darbepoetin then with GCSF. When these failed, I was lucky to be put on lenalidomide (tho not del5q). I have now been transfusion-independent for 5+ years, though my Hg has been gradually falling and the drug may well be losing effectiveness. Qun. Why are more patients not able to access lenalidomide, when MDS-005 showed that up to 25% respond positively? Is there any evidence that EPO can boost lenalidomide response when this begins to falter? Are there any other drugs in the pipeline for those who may eventually fail response to lenalidomide?
12:53 Dr Beth Payne: 
Lenalidomide is not yet licenced for non-del5q MDS. I would expect based on the study results the company will apply for a licence. Until then we cannot prescribe it out-with a clinical trial or via an individual patient funding request. I am not aware of an effect of the combination of lenalidomide and Epo. If you still have low risk disease and are becoming transfusion dependent again there are 2 main options – Campath (which is currently available on compassionate program ) and has response rates of around 30% or an individual funding request for azacitidine.
12:57 [Comment From Chris: ] 
The transformation from MDS to AML seems to be when there are more than 20% blasts. I have noted when searching on the internet that some patients quote a blast % range rather than a specific figure. How accurate is the measurement and are there any back up alternatives to confirm AML?
12:57 Dr Beth Payne: 
The principle reason for the variability in this is historical. In the older FAB (French/American/British) classification it was still MDS (RAEB-T) which between 20-30% blasts. In the current classification WHO (world health organisation) it is AML with >20%. Although the WHO is more widely used, many studies (including the azacitidine studies) use the FAB. In addition we sometimes see variations between the aspirate (liquid part) of a bone marrow and a trephine (bone core). In simple terms this is a spectrum rather than a black and white transformation.
12:59 [Comment From Donna: ] 
hello again, I currently receive three weekly blood transfusions and I am on Exjade, being low risk could I be part of your study? I did try EPO when I was first diagnosed but had no improvement with red blood cell, Thank you
12:59 Dr Beth Payne: 
Thanks for your interest. Unfortunately you cannot enter the study if you have already tried epo or have had more than 10 units of blood transfused.
1:01 [Comment From Dr.Moslemi: ] 
The best SCT is from sister or brother? Can we do on autolog method?
1:02 Dr Beth Payne: 

We don’t use autografting for MDS. Historically there was a study using autografts for AML and that study was open to recruit MDS patients with RAEB2 and above. In this study the autograft patients did not fare better than standard treatment or transplant although a subset of them did extremely well i do not know how many were MDS patients
1:06 [Comment From anna: ] 
I have a U2AF1 mutation and I am waiting to find out if it is germline as my Mother also had MDS. My 10/10 sibling is being tested too for this mutation.I appreciate there would 1/4 chance my children could get this mutation too but what makes a mutation cause MDS. My mother was in her 70's when diagnosed and I am 49?
1:06 Dr Beth Payne: 
U2AF1 has not been described as a germline mutation before. In principle at least 2 family members need to have this to consider this a possibility but in practice as you say your mum was quite old when diagnosed so it would be more difficult to be definitive about this. One possible route would be to try and get some DNA from your mum and see if she also carried the mutation if yours is found to be germline. This can sometimes be done on historical specimens depending on when and where she was diagnosed and treated. You are quite young for a diagnosis of MDS. Have you been tested for all the other familial predisposition genes ? Bear in mind that for some mutations just having a mutation only predisposes rather than causes (in other words not all individuals will be affected even if they have the mutation)
1:11 [Comment From Mark: ] 
Thank you I will check with Professor Jackson at the Freeman Hospital, I have an appointment with him on Friday. What is meant by primitive cells.
1:11 Dr Beth Payne: 

Primitive cells, or blast cells are the cells that indicate the disease is progressing towards a more aggressive form. Eventually when these cells make up more than 20% of the bone marrow we say this has transformed to acute myeloid leukaemia. This can sometimes happen very slowly or sometimes more abruptly. Some patients never transform but rather get gradually reducing number of cells requiring more blood product support. This may also be an indication to start treatment.
1:13 [Comment From Peter: ] 
Yesterday a grandson whom we see a lot,had his 3years 4 month MMR vaccine second dose and 4 in 1 pre school booster. I understand one of the doses is the live type. I am 4 years on from an unrelated successful SCT, would it still be wise to avoid seeing him or having contact for about a week.
1:13 Dr Beth Payne: 

Hi Peter – depends on whether you are still on immunosuppression or not and how long you have been off it. Probably best ring your team to check.
1:13 [Comment From Claudia: ] 
Can long-term transfusion dependency be a disadvantage in terms of access to clinical trials or new treatments?
1:14 Dr Beth Payne: 
Generally not Claudia. we do know that you are less likely to respond to epo if have been on long term transfusion but it is rare this is an exclusion for other studies
1:18 [Comment From Ted Peel: ] 
Hi, I was diagnosed MDS RCMD last year but have been feeling unwell for a few years. My neutophils have been very low and I am on GCSF injections three times a week. Apart from frequent infections my main problem is a sore throat and coughing up blood stained sputum, which occurs mostly at night. I have had many ENT investigations and ENT specialist believe the problem lies with my MDS. However, my MDS doctors do not think that is the case. Please can you offer any advice as I cannot sleep properly and am at the end of my tether? Regards Ted.
1:18 Dr Beth Payne: 
Hi Ted
Sorry to hear. It is difficult to advice without all your clinical information. You can get problems with platelet function even if the count is normal that can cause bleeding although this is quite unusual. It is not so unusual to have symptoms of general malaise with MDS. A scan of your chest would be helpful if you have not had one done and you should discuss this with your haematologist?
1:21 [Comment From Chris: ] 
Can you recommend any dietary advice to help MDS patients?
1:21 Dr Beth Payne: 
My general advice is to eat a generally healthy diet with plenty of fresh fruit and veg. While there is good evidence that “lifestyle” differences in diet (e.g vegetarian for life) can impact whether we develop some diseases including cancer there is no evidence to support changing your diet once you already have developed the disease. So eat well and enjoy it.
1:27 [Comment From anna: ] 
Thank you - What other familial predisposition genes are there?
1:27 Dr Beth Payne: 
There is a new diagnostic criteria in the revised world health organisation (WHO) classification which is called myeloid neoplasms with germline predisposition. This names the following genes. RUNX1, ETV6, ANKD26, CEBPA, DDX41, GATA2. However new ones are cropping up regularly. These can be tested for but some of the tests remain essentially on a research basis
1:30 [Comment From Russell: ] 
What has been the experience of Haplo vs MUD transplants? I was a Haplo on the 3rd attempt and my experience has been life changing - never been this healthy in 20 years
1:30 Dr Beth Payne: 

Thanks for your comment Russell. We generally still use MUD if 10/10 match over a haplo. However the results for haplos have improved remarkably in the past few years. I think we will see more of these in the future. Glad to hear you are well.
1:33 [Comment From Russell: ] 
What would your advice be to patients with regards Blood Transfusions and MDS? I know many are apprehensive. Are there are hard and fast rules as to when to transfuse?
1:34 Dr Beth Payne: 
No hard and fast rules. We use symptoms over number especially since the MDS patient may have other diagnoses that make them more likely to be symptomatic (e.g. heart problems). In general we do tend to be quite pro-active about iron chelation on those recieving transfusion to ensure we don’t run into problems with iron overload in those on long term transfusions
1:37 UCLH: 
That concludes the web chat! Thank you for all of your questions and apologies to those whose questions we were not able to answer today. We received a very high volume of questions.

If you would like to be referred to Dr Payne and the MDS team, ask your doctor or GP to write a referral letter to: Dr Beth Payne (Consultant Haematologist)
Department of Haematology
3rd Floor West
250 Euston Road
London, NW1 2PG
Wednesday July 6, 2016 1:37 UCLH
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