Professor Ghulam Mufti

Professor Mufti – whom many of you already know as his patients – is an internationally renowned specialist in MDS. He is the head of the haematology department at King’s College Hospital in London. He commenced his training in haematology at Radcliffe Infirmary, Oxford, and Hammersmith Hospital Royal Postgraduate Medical School. Because of his interest in pre-leukaemic states, in 1981 the Leukaemia Research Fund awarded him a fellowship in Bournemouth, Southampton & Royal Postgraduate Medical School. He was appointed as senior lecturer in haematological medicine and consultant haematologist in May 1985.

He has extensive clinical and research expertise in myelodysplastic syndromes (MDS), leukaemias, and lymphomas. The Unit at King’s is one of the leading centres for Bone Marrow Transplantation in MDS. He heads the research groups and works with a team of nine other professors who are experts in various medical fields including gene therapy, stem cell biology, bone marrow transplants, plasma cell dyscrasias and immunotherapy of myeloid malignancies, in particular MDS. Professor Mufti also leads 86 researchers who focus on treating leukaemia. He has published over 400 original papers and chapters in scientific journals and textbooks on leukaemias. He devised the prognostic score (Bournemouth score for MDS) and contributed to the IPSS scoring system. He was a member of the working group that produced national and international guidelines on the treatment and prognosis of MDS. He is a founding member of the Board of the International Myelodysplastic Foundation of which his Department at King’s College Hospital is a recognised Centre of Excellence.

Prof Mufti adds: “The MDS Newsletter is an emotional milestone for me, for MDS as a disease has at last come to the forefront of scientific and translational research. I am confident that the research will translate into real therapeutic benefit to all our MDS sufferers not just in the UK but worldwide.”

Lord Tariq Ahmad

Tariq Ahmad’s career has been in the City of London in corporate banking and marketing and currently serves as Marketing and Strategy Director at a leading commodity and financial futures and options firm, Sucden Financial, where he has been a member of executive team since 2004. A business graduate, he has extensive experience of financial services and the City spanning over almost 20 years. Joining NatWest in 1991, he spent almost 10 years with the Group in corporate banking and strategy roles before joining the US funds and investment house, Alliance Bernstein. Lord Ahmad, was Vice Chairman of the Conservative Party (2008-2010), has been active in local government in London, contested Croydon North in 2005 and became a Conservative Life Peer in the House of Lords in 2011. He is a Member of the Institute of Directors and is greatly involved in charity work.

We are very grateful to both for taking on this important role.

MDS UK Newsletter April 2012 Vol 2

We are now starting to collect newsletter articles for the next volume to appear in January 2013 and encourage all patients who may be interested to take part. Please contact us at the office if you are interested in contributing to Volume 3.

Dr Austin Kulasekararaj, Haematologist Consultant at King’s College Hospital, London kindly agreed to summarise the highlights of ASH 2011 for us.  He covered progress with existing therapies, promising trial data, new molecular mutations, as well as the revised IPSS (International Prognostic Scoring System).

MDS therapies

Combination therapy approaches both in low and high risk MDS was the focus of many presentations, building on the remarkable results obtained with 5-azacitidine and lenalidomide monotherapy.

A multicentre trial using combination therapy of 5-azacitidine (75 mg/m2 subcutaneously on days 1-5) plus lenalidomide (10 mg daily orally for 21 days out of 28 day cycle) in ‘high risk’ MDS patients showed response rate of 72%, with complete response seen in 42% and a median response duration of 16 months. The therapy was well tolerated with minimal toxicities (fever and cardiac) and significantly high response rates.

An interesting study from MD Anderson Cancer Centre assessed combination therapy of 5-azacitidine with vorinostat, a histone deactylase (HDAC) inhibitor in MDS and AML patients who were ineligible for another clinical trial or had liver or renal functions or had poor performance status. This combination was well tolerated in this ‘poor risk group’ of MDS patients with complete response rate of 26%.

Several other combination therapies of were studied in Phase 1 and Phase 2 trials, showing good tolerability and clinical activity

eg Panabinostat (HDAC inhibitor) plus 5-azacitidine,

Belinostat (HDAC inhibitor) and bortezomib (Velcade, proteosomal inhibitor)

Ezatiostat hydrochloride (Telintra) and lenalidomide (Revlimid)

Interestingly, studies using oral 5-azacitidine show good tolerability, with no drug accumulation, and promising clinical responses were observed, although these data are preliminary but the encouraging results show promise for oral azacitidine. A Phase 1 study also evaluated the safety of oral decitabine (Dacogen) in MDS patients and found to have a similar safety profile to intravenous decitabine.

A retrospective pooled analysis of MDS patients treated with lenalidomide (Revlimid) did not show a clear evidence that lenalidomide is associated with an increased risk of secondary cancers (second primary malignancies, SPMs) in lower risk MDS patients and the rate of development of SPMs was what would be expected for this age group when compared with US epidemiological database (SEER database). In another retrospective analysis of RBC transfusion-dependent patients with lower-risk MDS and del 5q, lenalidomide treatment was not associated with a higher risk of AML progression but led to a survival benefit.

Romiplostim (thrombopoietin agonists) showed an improvement in platelet count in one third of low risk MDS patients enrolled in a Phase 2 extension study, but unfortunately the trial was terminated early in view of transient increase in blast count which resolved when the drug was discontinued.

A few other selected studies presented included

• Home administration of 5-azacitidine (Vidaza) in France – showed feasibility, higher level of patient satisfaction and safety of administration. The home administration was not associated with increased side-effects or hospitalisation.
• Romiplostim (thrombopoietin agonists) to increase platelet counts after stem cell transplant.
• Role of azacitidine in Lenalidomide failure in del 5q MDS patients.
• Low dose clofarabine (5 mg/m2 vs. 7.5 mg/m2,dose finding study)-standard dose(D1 to D5) or alternate dosing (D1,D3,D5,D8 and D10), in patients failing 5-azacitidine therapy

The increased understanding of the molecular biology in MDS will help in future development of targeted therapies as the currently available therapies, although clinically effective, do not have a well-defined mechanism of action.

MDS pathogenesis

2011 has been an exciting year with the discovery of new class of molecular mutations in patients with myeloid neoplasms. The discovery of recurrent somatic mutations in RNA splicing factors in patients with MDS, especially in those with ring sideroblasts was highlighted in several presentations including the presidential symposium. Although the functional consequences of the altered splicing factors are being elucidated, this is a major breakthrough in the understanding of the pathogenesis of MDS with ring sideroblasts.

SF3B1 mutations are detected in 80-85% of patients with MDS associated with ring sideroblasts and is also present in 30% of patients with MDS overall. The mutations of the RNA splicing factors are the most common MDS-associated mutations yet to be described and these were detected as a result of whole genome/exome sequencing projects undertaken by several groups. Although SF3B1 mutations conferred a better prognosis, the prognostic impact of the other splicing factor mutations is not clear.

Prognostic models

IPSS-R

Recently, the provisional Revised International Prognostic Scoring System (IPSS-R) has been formulated for assessing the prognosis of primary MDS patients by the International working group for prognosis in MDS (IWG-PM). In this new system, as discussed by Dr.Greenberg in the MDS foundation symposium, cytogenetics remains the key stratification parameter and karyotypic abnormalities are classified into five prognostic subgroups with inclusion of more uncommon cytogenetic subsets. The depth of cytopenias was also considered and the information was obtained from 7012 patients who had not received any disease altering therapy. The IPSS-R divided MDS patients into 5 prognostic groups, with median overall survival of 8.7 years for very low risk group versus 0.8 years for the very high risk group. The value of incorporating of molecular abnormalities into the prognostic scoring systems was also debated and various groups also validated the impact of mutations on different prognostic scoring systems in MDS.

We are definitely achieving a better understanding of the mutations associated with MDS and refining risk model, but it is difficult to know just how any of these might translate into new therapies.

We thank Austin for his contribution to our scientific news.

This article deals with the need to develop cancer drugs that target specific gene mutations that develop in MDS.

Introduction: “By mapping the evolution of cancer cells in patients with myelodysplastic syndromes who later died of leukemia, Timothy Graubert, MD, and Matthew Walter, MD, from the Washington University in St. Louis, School of Medicine, have found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the disease.”

Read the full article, published 14/03/2012,  here.

• Red Blood Cell-Stimulating Agents May Improve Survival In Higher-Risk MDS Patients Receiving Vidaza 22/03/2012
• Researchers Identify Genetic Mutation Associated With MDS Progression 20/03/2012
• Panobinostat and Vidaza Combination May Be Effective In Higher-Risk MDS Patients (ASH 2011) 6/02/2012
• Lower-Risk MDS Patients May Benefit From Early Stem Cell Transplantation Without T-Cells (ASH 2011) 26/012012
• Home Administration Of Vidaza May Be Feasible For MDS Patients (ASH 2011) 19/01/2012

This is the link to the BBC Online site:

http://www.bbc.co.uk/news/health-17142568

For the AAT – this was the 6^th consecutive year – and for MDS UK – it was the second time.

We all had a fantastic day, with well over 100 people attending – walking or supporting the walkers and joining in the picnic afterwards.

There were options for a 6km, 10km and 16km walk.

The AAT (Aplastic Anaemia Trust) organised the day (brilliantly) – with signs, assistance, water stops, safety marshals, etc.  We thank Anna Martin and her team for all this hard work.  The registration donation of £5 went to the AAT to cover the costs of the organisation.

All of the MDS UK walkers and supporters then did an absolutely amazing job of getting sponsored to fundraise for MDSUK. The funds raised will be used to sustain the work and services offered by MDSUK.

We are still expecting some donations to come in – but we have already collected over £4,000 GBP – which is fantastic.

We thank everyone involved, walkers, supporters and all the very generous donors.

What will such a sum cover ?

To give you an idea of how valuable these funds are – with £4,000 we can :

• print and distribute our newsletter to hospital waiting rooms and to those patients who do not have internet access
• OR cover the costs of one of our annual patient information days – which are crucial to newly diagnosed patients
• OR use the funds towards our research project “Assessment for Support in MDS” Project – which will span the next 3 years.  So these £4,000 represent a very healthy contribution towards the costs of year 2.

So thank you very much again.

Our top fundraiser teams:

• Gwyneth and Andrew Brown-Lowe
• Team Sheath: Sue, Colin, David and Kate
• Karen Lynch
• The Celgene Walkers: Neha Dhadwal, Lisa Joyes, Alex Legg, Susan Larkin, Sara Barnes, Jacquie Harris, David Payne
• Team Taylor! Janet, Elaine Logan, Alice Hewitt – and super athletes David Hewitt (nearly 3 years old) and Lucas Hewitt who is a whole 1 year old!
• Claudia Richards & family

We would also like to post as many as possible of your photos on our website – please send them in to mds-uk@mds-foundation.org and we will upload them.  You can also add them to our MDS Facebook page.

You can still sponsor them – or send in any other donation to us. We will keep the Virgin Money Giving Windsor account open until the end of May 2012.

To sponsor a particular walker – please use our online donation site – and specify the name of the person:

Virginmoneygiving-Windsor-Walk

 Windsor Walk 2012

We need some volunteers to run to spread awareness of MDS – and raise funds to maintain our services to patients in future.

The ballot to get a public place is open for 9 days – until the 26th January and costs £45.

We can request some charity places – but they cost £120 each and we need to know that someone will run for us.

Let us know if you are interested please.

Here is the link for the public places and ballot:

http://royalparkshalf.com/ballot/

Thank you!!

Virgin Money Giving – who we use for donations – have a competition to win a potential £500 if the runner uses their fundraising page to collect donations.

Hurry up – as closing date is 26 Febr 2012!

Brighton Marathon fundraisers.  ‘Set up and Activate your Page Prize Draw’ is open to all fundraisers who have a confirmed place in the 2012 Brighton Marathon.

Even if you are not running – please promote this to all your contacts – in case they have a place in the Brighton Marathon and encourage them to set up their Brighton Marathon fundraising page with Virgin Money Giving.

http://uk.virginmoneygiving.com/fundraiser-web/fundraiser/fundraiserCharitySelectionOpen.action

Closing date for entries into the competition is 26 February 2012.

Please do let us know if you are running – we can provide logo, information, support – and we would like to include your details on the website – with photos and a brief message.

web: http://uk.virginmoneygiving.com  |   twitter: @vmgiving  |   blog: http://blog.virginmoneygiving.com

http://www.mdspatientsupport.org.uk/support-us/fund-raising/

“As a nurse I really want to see good individualised patient care within the NHS. Unfortunately this is not always the reality. Nurses are struggling to cope with the amount of patients allocated to them. Please support nurses with this campaign. So everyone realises nurses really want to care and do their job well. The Goverment just needs to give us the capacity to do our job. Thank you for reading.”

http://epetitions.direct.gov.uk/petitions/19157