In this section you’ll find testimonials from recipients of BSH grants. These testimonials show how our grants have helped them achieve goals, create networks and further their research.
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Dr Charles Bell, Bye Fellow (Medical Sciences), Murray Edwards College, Cambridge. College Teaching Associate, Queens' College, Cambridge. Foundation Doctor, University College London Hospital, London. Personal and CoTM Tutor, UCL Medical School, London.
Location of elective: Bhardwaj Research Laboratory, Icahn School of Medicine, Mount Sinai Hospital, New York City.
As part of my PhD, I focused on the role of a subset of natural killer (NK) cells, CD56bright NK cells, following IL-2 therapy - the elective period was spent principally learning new techniques and applying them in the context of a new scientific area of interest, the role of NK cell exhaustion in melanoma, in a collaborative laboratory environment.
This has enabled me to explore further a field of interest (cancer immunotherapy) whilst also giving me more laboratory experience in a different system, and a greater understanding of the translation of therapies from bench to bedside.
The Bhardwaj laboratory has extensively studied the tumour microenvironment in melanoma, to understand whether the cellular dysfunction seen in T cells is also present for natural killer (NK) cells.
In particular, these studies have focused on the immunoregulatory protein T-cell immunoglobulin and mucin domain containing molecule 3 (Tim3), a mediator of exhaustion in T cells, understanding its role in NK cells and whether exhaustion of this cell subset contributes to disease progression.
These cells reduce their cytokine secretion in the context of melanoma, and this project was to further investigate the profile of such putatively exhausted cells.
I also had the opportunity to spend time with clinicians and others in the translational pathway to more fully understand how these treatments were moving from bench to bedside, and to observe their effects on patients.
The sheer speed of development of new therapeutics and the very impressive remission rates using such drugs is remarkable, and the effects on patients are extremely dramatic, both in terms of life lengthening but also in terms of quality of life.
In addition, I was able to spend time becoming familiar with new forms of personalised medicine, for example the use of tissue biopsy and humanised mouse models of tumour growth to characterise the genetics and test therapies or particular drugs in the context of their specific disease.
At present the model is not fast enough to impact directly upon the individual patient’s care, but in the future the use of such techniques may revolutionise cancer care.
This elective gave me a fantastic opportunity to develop my PhD skills and knowledge into a new area – already having some skills developed in those years helped enormously, as I was able to immediately perform a number of experiments and pick up other techniques quickly. Working in a different environment from my PhD was also helpful, to really understand how different laboratories engage with the science, and the different research regulatory and academic environment was interesting to experience.
Overall, my elective most certainly did meet and exceed expectations. I am delighted to have gained a poster from the research period, I was made extremely welcome in the laboratory, and overall it must be said that New York City is a great place for both academic and social collaboration.
I would like to express my sincere gratitude to the British Society for Haematology, the University of Cambridge Clinical School (Hawkins Award), Queens’ College, Cambridge, the Royal College of Physicians, the British Medical and Dental Students’ Trust and the Gilchrist Trust for funding this amazing opportunity, and to Elena Gonzalez-Gugel and Nina Bhardwaj for their supervision, support and for making this possible.
Elliot Byford, 4th Year Medical Student at the University of East Anglia
Location of elective: Nagoya University Hospital, Nagoya, Japan
I would like to say an enormous thank you to The British Society for Haematology for supporting me financially during my medical school elective.
Throughout my studies at medical school, I have always found haematology to be an incredibly enjoyable and stimulating speciality, and have seen it as a potential career for some time. My elective was a fantastic chance for me to build on this interest: I chose to spend two weeks in the haematology and oncology department of Nagoya University Hospital in the city of Nagoya, Japan, which doubled as a chance for me to develop my interest in Japan and the Japanese language.
I have nothing but good things to say about my experience - right from the start of my placement I was blown away by the kindness and hospitality shown to me. I quickly learnt that there is a strong team dynamic in Japanese medicine, and was always made to feel valued and included in that team. Staff continually went out of their way to provide teaching in English for me, and took a genuine interest in me which I really appreciated.
I was able to move across the entire department and take advantage of a wide range of different learning opportunities which was very exciting. From a clinical perspective, I was able to engage with the management of a varied mixture of common and rare diseases, and really enjoyed following patient’s progress over the two weeks. A particular highlight was getting the chance to witness a number of stem cell transplant procedures and learn a great deal about transfusion medicine. I also saw paediatric haematological cases – these are areas that I had no experience of during my placements in the UK.
Outside of the clinic, I was struck by the emphasis placed on research in university hospitals in Japan. Clinical work and research seemed almost interlinked, as the offices of the entire department were physically combined with a research laboratory. Every doctor had their own research projects ongoing alongside their clinical practice.
I had the opportunity to work with doctors while they were doing their research, and this was my favourite part of the elective as until then I had no real experience of research. This work also helped prepare me for the intercalated BSc in Haematology Research that I was due to undertake the next year.
I also joined in with departmental meetings and was able to give a presentation to Japanese medical students on my experience to encourage them to seek training abroad.
From a wider perspective, one of my main goals for my elective was to experience an alternative healthcare system, and compare it the NHS. As a developed country, Japan has many subtle but important differences in aspects such as economics, where a percentage of all treatment is usually paid for by the patient, and the extensive use of technology, for example almost all notes were typed instead of hand-written.
I was particularly interested in the logistical aspects of Japan’s hospital-based healthcare system which places much less emphasis on general practice / family medicine than the NHS, and the effects that this has on patient care.
Overall, my elective was a great educational experience and I was sad to say farewell to the team. I was able to expand on and consolidate my haematology knowledge, and it really strengthened my desire to engage with the specialty in the future.
Rory Graham, 5th year medical student at Glasgow University
Location of elective: Schiehallion Ward, Royal Children's Hospital Glasgow
'Paediatric oncology with interest in haematology' at the Royal Children's Hospital Glasgow was a four week venture into the Schiehallion ward. Under the supervision of Dr Ronghe I was able to diversify my learning between the three specialties that share the ward; oncology, haematology and transplant medicine. Partaking in ward rounds and clinics of these three specialities as well as visits to the lab and apheresis unit at Gartnaval Hospital I was able to see a vast amount in four weeks.
In addition, I completed two projects; an audit in paediatric neuroblastoma patients and to complement this I completed a spreadsheet program to provide dates for a treatment plan for paediatric patients with neuroblastoma.
The core outcomes from my elective were to learn how paediatric medicine differs from adult, and to contribute to the field by completing an audit. During the completion of these educational outcomes I would learn through exposure to different scenarios how a paediatric doctor fulfils his duty of care to his patients. Observing the interplay of different health professionals would in turn add to my growing understanding of what it means to be a health professional.
My supervisor, paediatric consultant Dr Ronghe, listened to my goals and ensured I could access to the right people and facilities to achieve them. This introduced me to Dr Kenneth Douglas, consultant haematologist, who explained to me the challenges of treating paediatric neuroblastoma. This became my audit subject.
Treatment is guided by the SIOPEN trial, which dictates whether the patient receives the N7 or COJEC chemotherapy. Peripheral blood stem cell transplant is a critical component in the treatment of neuroblastoma patients as this ensures adequate populations of progenitor blood stem cells remain in the bone marrow of the patient. These cells are collected after chemotherapy once the bone marrow has had a chance to recover. However, the limited success of PBSC collections is thought to be contributed to by the design of the trial. My audit therefore centred on gathering data of which mobilising chemotherapy achieved the most successful PBSC collections.
In addition to my audit project another doctor provided me with a brief on a second project. He stated there was a need for a program that effectively planned each stage of the treatment protocol for the SIOPEN trail. What resulted was a program that required one date for starting chemotherapy. The code was such that an alteration in any of the dates, for example a delayed chemotherapy treatment due to line sepsis, would result in a rescheduling of all other dates to the new timetable. In this way a plan was available to both the healthcare team and the parents of the patient.
I was proud of the final product as when I took on the project I was not confident using excel to this end. I used my initiative and at the same time gained an understanding about trial design that will benefit me in interpreting the complex details of some trials.
Delving into this audit I developed my understanding of a new area of oncology. Neuroblastoma is an example of malignancy of embryonic stem cells. I understand now why blastoma type cancers are prevalent in children and how they are treated differently. This linked to the necessity of PBSC transplants in the treatment protocol.
Learning about PBSC transplants provided a link between oncology and haematology, my special interest. Autologous transplants are different to allogenic transplants as the aim is to encourage regrowth of the patient’s native immune cells, in contrast to using the graft vs host effect to attack cancer cells.
Transplant and oncology specialities work together efficiently and communication is aided by sharing the same ward. MDTs are held daily and care is highly co-ordinated. I noted in particular how tightly care was co-ordinated and how this translated into benefit for the patient and their family. Parents were kept so well informed; in essence the doctor-parent relationship was the basis for a greater trust placed on the doctor than I had seen before.
The weight of responsibility on the doctors was intense. Occasionally the doctors’ room was a place for consolation following conversations on dolorous topics with parents. The doctor must inform the patients carers in such a way to allow them to make decisions that may result in the death of their own child. The parent places trust in the doctor’s knowledge, their opinion, and in the specialty as a whole. It was humbling to have had even a small role in the care of any patient. The privilege of treating any sick patient is something I never want to lose hold of in my career. Taking responsibility over the care of a human in the most vulnerable period of their life is a humbling experience.
The weight of the responsibility can be shared among the members of the team. Everyone in a team has a different background and views, but in Schiehallion I saw them brought together by their duty of care for their patients. The strength of a team comes from the safety they feel in their job. The confidence to make decisions does not come entirely from knowledge and experience, but also from the assurance received from being part of a dependable and cohesive team.
Ideally I would have liked to have completed my paediatric block prior to my elective as this would have given me a greater appreciation to just how different a paediatric speciality is compared to adult medicine.
I feel the most enjoyable aspect about an elective is the freedom to explore the areas you are passionate about without the restrictions placed on you to complete cases and course work. I am a student who works best with minimal guidance and the audit work and excel program I designed ware examples of my best work. I had a task and a deadline, I planned as best as I could and got the job done. The confidence that I have gained from looking back at my work and seeing that I have made a difference, seeing what I can do when I grasp opportunities, will be something I wholeheartedly take forward in my quick approaching professional life.
Report from the 57th American Society for Hematology meeting, Orlando, December 2015
“It has spurred me on further to embark on a career in haematology”
I was privileged to be selected to present a poster at the 57th ASH Annual Meeting in Orlando, Florida. This was a good opportunity to practise making a poster for a professional, rather than student conference, of which I had several experiences previously.
Whilst I was there, I had a reasonable level of interest in the poster and had a discussion with a few delegates from around the world who were interested in my research. I was pleased to be able to engage with people far more senior than myself on a complex topic. I got a few pointers in other areas of the subject to explore, which will be useful prior to writing the research up as a paper.
The annual meeting was a fantastic opportunity to network with other delegates. Including several haematology consultants and senior doctors at Salford Royal Hospital, The Christie and Manchester Royal Infirmary, as well as researchers, doctors and representatives who I met at pharmaceutical company meals.
I attended many fascinating lectures during the conference, from novel methods to reduce infection and graft-versus-host disease post-bone marrow transplantation, to targeted inhibition of mutated proteins in acute myeloid leukaemia (such as midostaurin which was one of the big revelations at the meeting), novel combination induction therapies in myeloma, as well as efficacy of checkpoint inhibitors in relapsed/refractory lymphoma. I predominantly attended talks relating to haematological malignancy as this is my main area of interest. I aimed to get an update of the new clinical trials featuring novel agents and combinations thereof.
Some talks were very relevant for new projects that I am currently undertaking and have given me ideas on directions in which I want to take them. It was inspirational to listen to talks by some of the world experts in their chosen fields, which has spurred me on further to embark on a career in haematology.
I would like to take the opportunity once again to thank the British Society for haematology for its support in the provision of funding to allow me to attend this conference, as without this I would have found it very difficult to find the money to go. This was an invaluable experience, and I will be seeking other opportunities in future to present my research and to update my knowledge.
Deadline to apply for an ASH Travel Scholarship is 9 October 2017 - Follow this link to apply.
Report from the 57th American Society for Hematology meeting, Orlando, December 2015
'Attending ASH 2015 has helped me to become a better haematologist'
The financial support provided by the BSH Travel Scholarship enabled me to travel to Orlando to present my abstract 'Poor outcomes in HIV positive and HIV negative plasmablastic (PBL) lymphoma in a Population Based Study' at the poster session on Monday 7th December. This abstract represented the culmination of six months’ work on this poor risk patient group. I gained valuable experience in preparing my work for presentation and summarising the key findings for an international audience.
At the meeting, I was struck by the number of clinicians and pathologists from around the world who had similar experiences with this patient group; primary refractory disease and short overall survival being the predominant features. I also received informal feedback on the project which will be useful in preparing the manuscript for publication.
The Education Sessions at ASH are recognised as a major learning resource for trainees and experienced clinicians. They tackled key issues affecting patients with benign and malignant haematological disease and provided evidence based management strategies from problems as diverse as how to approach an incidentally diagnosed pulmonary embolism to the role of BRAF inhibition in histiocytic diseases. The new emphasis on patient reported outcomes and palliative care for terminal disease is welcome, and will assist me in future to choose therapies that positively impact on patients’ quality of life.
Attending ASH 2015 has helped me to become a better haematologist and I would like to re-iterate my gratitude for the support received to permit me to attend.
Deadline to apply for an ASH Travel Scholarship is 9 October 2017 - Follow this link to apply.
BSH Travel Scholarship supported Dr Willmore to attend International Workshop in New York
I’m very grateful to BSH for the travel grant to support my attendance at the international workshop on Chronic Lymphocytic Leukaemia (CLL) in May, 2017. The workshop is a 4 day meeting with a blend of clinical/translation studies and basic biology, with the aim of advancing the understanding and treatment of CLL (and associated malignancies).
The workshop opened with sessions focused on the factors leading to the development of CLL, including a description of familial CLL (Tait Shanafelt) describing how 10% of patients have first degree relatives with CLL. Monoclonal B-cell lymphocytosis (MBL) may also contribute to the development of CLL and genome-wide studies have identified 9 loci that are associated with an increased risk for CLL. Richard Houlston explained how SNPs conferring risk for CLL map to areas of open chromatin where they may be involved in regulation of gene expression.
At the meeting, I also had the opportunity to present a poster entitled “Activation of p53 by the MDM2 antagonist RG7388 in CLL cells ex vivo triggers cell death via a pro-apoptotic gene signature”. The poster describes part of our recent work from the Cancer Research UK Drug Discovery Newcastle team, who are working in alliance with Astex Pharmaceuticals. We are investigating how MDM2 antagonists may be used in CLL, particularly as this represents a non-genotoxic therapy with minimal effect on normal cells. The poster was well received and gave me the opportunity to engage with others in the field and consider possible combination therapies using MDM2 antagonists.
Finally, these relatively small workshops facilitate interaction, and I was able to meet with two collaborators to discuss recent data and progress future directions with novel small molecule inhibitors that are of mutual interest. Many thanks to BSH for this award, which was much appreciated.
Deadline for Travel Scholarship applications is 31 July. To apply, please visit this link.
BSH Student Elective Grant supported Sunay Gangadharan to travel to Kerala, India
Firstly, I would like to thank the British Society for Haematology for sponsoring this period of elective study.
I carried out my elective in the state of Kerala, tucked away in the southwestern corner of India. I chose Kerala as my elective location as it is the place of my parents’ origin and from previous visits to the India, it is somewhere I can identify myself with culturally. I was intrigued by the ‘Kerala model’ of development which has seen the state achieve the best living conditions in all of India. With only 3% of India’s population, this diminutive state excels in indicators of social development such as low levels of infant mortality and population growth; the highest levels of literacy in the country, particularly among females; and higher life expectancy relative to the whole Indian population. These statistics are made even more impressive considering such indicators are comparable to many developed countries despite Kerala’s per capita income being much lower in
comparison. I wanted to explore the basis for the state’s impressive health standards and compare it to the National Health Service in the UK.
Unfortunately, Kerala is reported to have the highest number of cancer patients in the country. I wanted to study whether cancer care was proficient in Kerala so I decided to visit the Regional Cancer Centre (RCC), in the state capital Thiruvananthapuram. The RCC is an autonomous scientific institution sponsored jointly by the government of Kerala and the government of India, which prides itself on being an internationally recognised centre providing state-of-the-art care. I also had a specific interest in haematological malignancies and was allocated to observe in the Medical Oncology department. I was expected to attend the morning ward round where majority of patients were diagnosed with with either Acute Myeloid Leukaemia (AML), Acute Lymphoblastic Leukaemia (ALL) or Non-Hodgkin Lymphoma. Just as in the UK, all three are present in the top
twenty types of cancer. The ward looked barren, the only cooling was from ceiling fans and there were no curtains between patients’ beds.
The ward round consisted of a senior resident and a nurse working in a pair, each reviewing the female and male bays, during which time each of the three consultants would pop in at various periods to check on their individual patients. The senior resident would check any outstanding blood results, palpate for any new lymphadenopathy, look inside the mouth for fungal infection and auscultate the chest for signs of respiratory disease. Once the rounds were completed, I was afforded the opportunity to observe patients receiving lumbar punctures and administration of intrathecal methotrexate as part of their chemotherapy regimen. The residents were amicable and keen to explain the intricacies of the various chemotherapy protocols.
I was briefed about routine investigations such as blood tests and what important parameters to look out for. I was able to observe how diagnostic methods were being employed in the laboratory. Bone marrow studies helped to identify possible chromosomal translocations and flow cytometry classified various cell populations that were used to identify types of leukaemia. Newer techniques such as fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) required in the identification of the Philadelphia chromosome were also shown to me.
During the afternoons, I was expected to attend outpatient clinics and these were undoubtedly the highlight of my trip. The outpatients department consisted of two consulting rooms with a room dedicated to procedures adjacent to them. The rooms were swelteringly hot and there were no facilities for cooling. Each room was smaller than the size of standard NHS consulting room and personnel were split with consultants being in one room seeing follow-up patients and junior doctors in the other clerking in new patients. There would always be 3 doctors in each tiny room working simultaneously, and up to 10 patients in a room including patients, nurses and relatives. I was overwhelmed by the turnover of patients within the department; one could argue it is up to three times as efficient as an NHS outpatient clinic despite there being a complete disregard for patient confidentiality. On my first day, I was handed a pile of new patient notes and was asked to call in patients to be clerked while being supervised by one of the postgraduate doctors. I found it extremely challenging to clerk patients in my native language Malayalam – even though I was reasonably fluent conversing with the local population, explaining or asking complicated medical concepts was a struggle and fortunately my supervisors often came to my rescue.
There are vast differences in practice between the UK and India regarding communication from caregivers. I was present when bad news was broken to a patient about a cancer diagnosis in what seemed like an insensitive manner, without the classical ‘warning shot’ we are taught at medical school. The patient felt understandably devastated and being the breadwinner from a modest farming family, was fearful about the cost of treatment. Fortunately, at RCC cancer treatment is subsidised by the Indian government with more funding available for those on lower income.
There has been much discussion over the role of Ayurveda in cancer treatment. It is an ancient Indian system of medicine involving therapies based in complex herbal compounds, prayer, meditation and nutritional supplements as a means of healing from cancer. According to Cancer Research UK, there is no scientific evidence to prove Ayurveda can treat cancer. Experts at RCC I spoke to corroborated this conclusion and further went on to mention how some patients try
alternative treatments first due to their perception of the financial burden a cancer diagnosis may create, which then go on to fail, resulting in patients presenting late at a stage their disease cannot be cured.
Overall, I have enjoyed my trip to Kerala. The weather was fantastic, the people were a joy to work with and the food was both delicious and cheap! I was exposed to a wide variety of clinical presentations and I was able to gain a lot of valuable hands-on experience. Being thrown into the deep end by being asked to communicate in a different language, diagnose and work out appropriate treatment strategies proved to be an important character building experiences. I will definitely be carrying forward these positive experiences into my own clinical practice.
I used the BSH grant to fund my elective and I went on elective India I went to our medical Kerala which is where my parents I've been together a few times but never experienced the healthcare system and I was particularly interested in how cancers were treated in particular blood cancers in that part of the world. I was looking for funding the negative and I happened to do an internet search for funding and I found it on I think it was a website called money for medical students and I found BSH and they were the requirements were very very few so yeah i just played for it and they wanted a report or some evidence of academic standing and one extra curriculae activities I participate in and yet they accepted my request to the BSH opened a lot of doors for me and I'll be able to go and see things in my chosen country that I probably wouldn't have had the opportunity to see such as lab experience able to paymore money into seeing things such as FISH and sky procedures are done in the laboratories which is probably not accessible to see in the UK unless you get special permission so that's that's really helped me a lot. The highlight of my elective was going to an outpatient clinic my first day and given a stack of notes and being asked to clock in patients in a totally different language that was a great experience. BSH group has changed my experience of haematology being able to see various presentations of haematology things I had never seen in the UK and it allowed me to see things that probably I'd never see again in my lifetime and I'm very grateful to the British Society of Haematology for that.
The American Association for Cancer Research (AACR) Annual General Meeting brings together cancer researchers from all fields and locations to present, discuss and share the latest advances and developments in cancer research.
A major focus of this meeting was on novel drugs and drug targets, for example CDK9. Inhibitors of cyclin-dependent kinases have been explored for some time; however, most compounds currently in trials are pan-CDK inhibitors with little selectivity over one isoform. CDK9/PTEFb is a positive regulator of myc, an oncogene overexpressed in several cancers and BAY1143572 is a potent inhibitor of CDK9/PTEFb. In vitro, BAY1143572 decreased MYC protein and mRNA and induced apoptosis, and in vivo it completely prevented tumour growth in a MOLM2 AML xenograft model and partial responses were also observed in myc-amplified Snu16 xenograft models. The compound is currently in phase I trials and myc mRNA is being evaluated as a PD biomarker.
In addition to novel drug targets, there were several talks on resistance and resistance mechanism. One example are tyrosine kinase inhibitors such as imatinib and nilotinib, which have substantially advanced the treatment of bcr-abl-positive CML. As resistance to these often emerges due to mutations in the ATP-binding site of the bcr-abl catalytic domain, an approach to targeting imatinib-resistant CML is allosteric inhibition of bcr-abl. A novel compound ABL001 was found to negatively regulate the bcr-abl kinase activity without affecting the ATP-binding site, and this compound inhibited growth of bcr-abl-positive CML and ALL cell lines, including those resistant to imatinib. In vivo, ABL001 lead to tumour regression in KCL-22 xenografts, although tumours eventually relapsed, similar to nilotinib as a single agent. A combination of the two drugs however was found to be highly effective and prevented relapse for over 100 days after treatment was stopped.
Another much-discussed topic at this meeting was cancer immunotherapy, the concept of generating tumour-specific memory T-cells which phagocytose tumour cells. Agonists of OX40 can co-stimulate effector T-cells while inhibiting regulatory T-cells, downregulating regulatory T-cell-mediated suppression of the immune response, suggesting that OX40-agonists could potentially induce this tumour-specific memory. Indeed, after three weeks of treatment with a mouse humanised anti-OX40 antibody (MOXR0916), tumour regression in vivo was seen and even when re-challenged with the same tumour, animals remained sensitive.
Finally, dedicated meet-the-expert sessions offered great opportunity for in-depth discussion of specific subjects. One session was focused on myeloma and provided an excellent update on the current understanding of the disease and its treatment and also discussed experimental therapies. Current combinations of proteasome inhibitors (bortezomib, ixazomib) with dexamethasone and lenalidomide induce high response rates, but poor prognosis patients such as those with del17p remain at risk. All proteasome inhibitors induce upregulation of AKT so inhibitors of ATK signalling could potentially be clinically useful in the future.
All in all, this has been a very useful and informative meeting. As well providing an excellent update on work in my own field, this meeting has been a brilliant opportunity to network with other cancer research scientists as well as broaden my horizons and gain some insight into the broad range of research topics in cancer research. I am very grateful to the BSH for their support which allowed me to attend this conference.
For my medical school elective I undertook a four-week clerkship in Haematology at Emory University, at their affiliated hospital, the Atlanta Veterans Association Medical Center. I was able to do this thanks to the generous bursary awarded to me by the British Society for Haematology. Overall, the placement proved to be a fantastic learning experience, and I now feel in a strong position from which to pursue my intended career in Haematology. I hope to have a career as a clinician scientist, combining patient care with clinical research.
I spent time with both the inpatient and outpatient services, and through these saw patients with many of the most common haematological conditions, both malignant and non-malignant. I learnt about the staging and prognosis of common haematological malignancies, and about the principles of investigation and management of common haematological presentations such as anaemia, thrombocytopaenia and coagulopathy. I took responsibility for my own inpatients, clerking new patients, presenting to the Attending Physician and, with their guidance, formulating a management plan and documenting the consult in the patient’s notes. I then reviewed the patients daily, checking their test results, doing a physical examination and presenting them on the daily ward round.
I was lucky to see an unusual case of a very rare disease, POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes). I was the first person from the Haematology team to clerk this patient, and was closely involved in the investigation and diagnosis of his disease. It proved to be a very interesting case, with a number of useful learning points about the management and investigation of patients with unexplained and refractory symptoms. I therefore volunteered to write up the case with help from the Attending Physician, and we have submitted it for publication in the journal BMJ Case Reports.
In addition to clinical activities, I attended teaching sessions and departmental meetings, including a weekly multidisciplinary ‘tumour board’, radiation oncology case discussions, and grand rounds. I also spent time with the haemato pathologists, learning about basic morphology of normal and abnormal blood and bone marrow, and the interpretation of blood smears, bone marrow aspirates and core biopsies, and lymph node biopsies.
Despite having had very good clinical experience through my main syllabus, the frequently changing rotations meant that this elective was the first time I felt I’d really seen patients through several stages of their medical care. Sadly, this included a number of patients with aggressive and difficult malignancies, and four of our inpatients died during my placement. This was my first experience of patients that I felt I knew well passing on. It was a privilege, and an important learning experience, to have been part of these patients’ end of life care, and to have been involved in discussions with them and their families about this critical point of their medical care.
I was also interested to observe some of the differences between the British and American healthcare systems. I had the opportunity to discuss issues regarding health insurance and payment for treatment with both physicians and patients, an experience that very much reinforced my belief in the National Health Service. Another striking difference was in protocol regarding consent for treatment. Written consent is required for a greater number of minor procedures in the US, and, in the event that the person lacks capacity, it must be obtained from their next-of-kin. In one case that I saw, this was from an estranged ex-wife. This differs from the UK, where if a person lacks capacity, doctors must act in best interests, and no one can provide consent on behalf of another adult. The American physicians were surprised to hear about our system, and felt this was overly paternalistic. However, my impression was that gaining consent from next-of-kin is often inappropriate, and that the practice may reflect a need for physicians to protect themselves against the more litigious nature of American society.
I worked closely with the team’s physician assistant (PA), which was interesting in light of the current drive to recruit American PAs to the UK, in an attempt to address the widespread issues of medical staff shortage. There has been some backlash in the British medical community against this decision, with objections to the fact that PAs do less higher education and training than doctors and are being offered higher salaries than junior doctors. My experience, however, was entirely positive. Our PA was extremely knowledgeable and competent, and, far from threatening the role of the junior doctors, provided invaluable support. Moreover, whilst the junior doctors rotated through the department every couple of months, the PA was a permanent member of staff. She therefore not only provided a valuable source of information and training for each new wave of junior doctors, but also provided the patients with a constant presence throughout their long treatments.
Altogether, the bursary awarded to me by the British Society for Haematology provided me with a fantastic opportunity to gain an in-depth experience of the clinical specialty of Haematology, which is regrettably lacking in the main syllabus of my university course. It also gave me an interesting insight into one of the most technologically and academically advanced and progressive healthcare systems in the world, but one that is very different from the NHS. I feel I have gained a deeper understanding of the American healthcare system, and of its strengths and weaknesses compared to the NHS.
International Meeting on Translational Research in Malignant Lymphoma
I am very grateful to the BSH for sponsoring my attendance at this international meeting that focused on translational research in malignant lymphoma.
I found my oral presentation particularly rewarding in that it stimulated discussion with international experts, raised the possibility of collaboration and focused our plan for publication.
I used the opportunity to update myself on contemporary research findings, clinical trial outcomes and to familiarise myself with new concepts that are likely to affect clinical management in the near future.
The conference was opened by Professor Cavalli, who introduced Lois Staudt to deliver the Henry Kaplan Memorial Lecture entitled ’Therapy of Lymphoma Inspired by Functional and Structural Genomics’. Professor Staudt summarised the key biological differences between Germinal Centre (GC) and Activated B Cell (ABC) Diffuse Large B Cell Lymphoma (DLBCL) that are particularly relevant in the era of B Cell receptor targeted therapies. He emphasised the importance of antigen engagement leading to NFkB activation that is sensitive to BTK inhibition in ABC-DLBCL.
Peter Johnson reported the first analysis of the RATHL Study (Response adapted therapy based on interim FDG-PET scans in advanced Hodgkin’s Lymphoma).
This trial recruited 1214 patients and found that omission of bleomycin in the context of a negative interim PET reduced pulmonary toxicity without compromising progression free survival (PFS) at three years. Escalation of therapy in the context of a positive interim PET achieved a three year PFS of 68% regardless of the regimen used (3 x eBEACOPP or 4 x BEACOPP-14).
Professor Ferreri reported that the addition of Thiotepa and Rituximab to Methotrexate and Cytarabine increased the ORR to 72% and the CR rate to 34% with a trend towards increased PFS, albeit with increased haematological toxicity. Results of the second randomisation to whole brain radiotherapy or autologous stem cell transplantation are awaited.
Lastly, Professor Timmerman presented the updated results of a Phase 1 study of Nivolumab (PD-1 inhibitor) in relapsed / refractory lymphoid malignancy and Classical Hodgkin Lymphoma (cHL). Although the number of patients (heavily pre-treated) enrolled is small, the drug appears to be particularly effective in cHL with 26% patients achieving CR. The main safety consideration is drug-related pneumonitis, affecting >5%.
Prof Dalla-Favera from Columbia University discussed lymphomagenesis, and emphasised the role of genetic lesions that contribute to the evolution of FL and DLBCL and how these may translate into specific therapeutic strategies.
Recurrent somatic mutations in Exportin 1 are found in primary mediastinal B cell lymphoma.
Recurrent somatic mutations underpin the ABC (NFkB pathway), GC (epigenetic pathway) and PMBL (JAK-STAT and immunity) DLBCL and will inform targeted therapies.
I presented my oral abstract (053):
In-Vivo Studies of Kinetics In CLL Provide Definitive Evidence of Lymph-node Re-entry and Suggest that there is a Non-proliferative Subclone.
Professor Hallek asked about the relevance of the finding of a non-proliferative sub-clone in the era of BTK inhibition.
Professor Wiestner emphasised the point that we are the first group to find evidence of lymph-node re-entry and emphasised the importance of replicating this result.
Ibrutinib – Clinical Trials
Peter Thornton presented an update in the results of Resonate Study of Ibrutinib versus Ofatumumab in relapsed/ refractory CLL.
PFS at 12 months – 84% for Ibrutinib versus 18% for Ofatumumab. PFS advantage is independent of genetics, complex karyotype or number of prior therapies.
Steve Treon reported the first prospective trial of Ibrutinib in relapsed/refractory WM. Major responses were highest in the group with mutated MYD88 and wtCXCR4. wtMYD88 and wtCXCR4 was associated with inferior PFS.
Chronic Lymphocytic Leukaemia – Treatment
Overview of experience of Ibrutinib, Idelalisib and ABT-199 presented by Susan O’Brien. Clinical discussion re management of side effects.
Professor Kuppers gave an update on the current understanding of biology of HD including relevance of gene expression and sequencing studies.
Imaging in Hodgkin’s Lymphoma
PET score following 3 cycles of ABVD has greater prognostic significance that pre-treatment PET evaluation in RAPID trial of early HL.
This finding will be further investigated in future trials.
Consolidation with Brentuximab Vedotin post ASCT improved PFS in primary refractory patients compared with historical controls.
Risk of transformation of FL and outcome in the Immunochemotherpay Era: Ancillary Study from PRIMA trial (addition of maintenance Rituximab in patients treated with R-chemo). Risk of HT = 1.5% per year. Patients have a poor response to salvage therapies but ASCT has a role when feasible.
Primary results from Phase III Gadolin Study of Obinotuzumab plus Bendamustine versus Bendamustine alone in Rituximab Refractory NHL. G +B followed by G maintenance improves PFS versus B alone (23 versus 14 months).
Andrew McMillan presented data from the phase II study of R-CODOX-MIVAC for unselected patients with high/intermediate or high risk IPI. 131 patients have been treated and it appears that there may be a PFS advantage over P-CHOP, although further follow up is required.
Current immunotherapies under investigation include engineered antibodies, antibody-drug conjugates, bi-specific antibodies and CAR T cells.
Jack C Dean
I would like to thank the BSH for providing a grant of £300 to cover the cost of
commuting to my six-week elective placement at the Centre for Haematology, Imperial College London. I was fortunate to be able to work in a supportive research group headed by Dr Holger Auner on the fundamental biology of endoplasmic reticulum stress induced in cancer cells by novel small molecule inhibitors. This research has particular relevance to the development of future targeted therapeutic regimes for Multiple Myeloma.
My elective placement provided an excellent opportunity to familiarise myself with a new field of research within Haematology and to learn new techniques in the laboratory. I was able to design simple experiments, and using these techniques, acquire and analyse a small amount of preliminary data, which has provided some novel information. During my time at the centre, I was also able to attend all research group and journal clubs meetings. In addition, I attended symposia delivered by outside speakers.
Overall, my elective placement has improved my confidence in appraising scientific literature, basic laboratory techniques and analysing data. My elective placement has also complemented my most recent clinical placement in Haematology back at my home medical school. I have written a project report for my home medical school. Furthermore, I hope this experience will strengthen my upcoming application to the Academic Foundation Programme.
My student elective was spent at Gizo hospital, on Gizo Island, in the Western Province of the Solomon Islands. The Solomon Islands are an archipelago of around 900 islands in the South Pacific. A former British colony, they gained independence in 1978. There is a democratic system of government and recently the country has been largely peaceful, with the exception of racial tension and violence which broke out in the capital Honiara around 2000. 80% of Solomon islanders participate in a sustenance economy, so while there is little food poverty, the nation is possibly the most resource-poor Pacific nation.
My aims were as follows:
Complete a multi-faceted project on blood transfusion at Gizo hospital which will consist of the following components:
- A case study of the entire process of blood donation and transfusion in Gizo hospital, identifying potential causes of adverse outcomes.
- Audit of outcomes or processes identified in the case study.
- Recommendations of feasible changes which could be made to the service with reference to the WHO Clinical Transfusion Process and Patient Safety document.
Develop my clinical skills and knowledge.
Gain experience of healthcare provision in a developing country.
Contribute to the running of the hospital.
Overall I found the elective a profoundly rich experience, which taught me much about clinical medicine in addition to research and ‘capacity building’ in low income countries. Furthermore, it has placed medicine in its global context and stimulated thoughts about my career.
Although my elective was split between clinical activities and a project on blood transfusion, my report focuses on blood systems, as a short reflection followed by an abbreviation of my formal report.
Gizo has an 80 bed hospital recently built by the Japanese, following the destruction of the previous building by a large tsunami in 2007. There is an operating theatre, dental theatre, emergency room, and outpatient department with space for physiotherapy, diabetes clinic, and eye clinic. There is a lab with an automatic analyser for blood counts and radiology department with ultrasound and X-Ray.
There are three local doctors who carry out minor surgical procedures such as excisions and drainage, in addition to tubal ligations, caesarean sections, and any emergency surgery such as ruptured ectopic pregnancies and appendectomies. Major elective operations are referred to the capital, Honiara.
Blood Donation & Transfusion
When I arrived in Gizo, I began to make enquiries about the local and national blood systems. The pathologists, who are professionals trained in laboratory medicine, take responsibility for blood donation and transfusion. I liaised very closely with the two pathologists at Gizo hospital throughout my time there.
My work on transfusion was heavily informed by conversations I had with various professionals and local people, in and outside the hospital, including doctors, nurses, pathologists, local Red Cross staff, and representatives for the department of health in the capital, Honiara. At times this was frustrating as many professionals were not particularly engaging. There are still gaps in my understanding of the blood system in Honiara as a result of these difficulties.
In Gizo there are no computerised records, and no centralised patient records, nor are there protocols or written standards for donation or transfusion. Furthermore, as the staff initially informed me that Gizo hospital performed only one transfusion per week I did not believe I would be able to collect enough data for a meaningful audit. However, I later discovered that one of the pathologists had begun collecting data on local transfusions, and this information proved invaluable for evaluating the effectiveness and safety of the current system and informing my recommendations.
In my penultimate week the hospital invited me to present my findings, which I followed with a discussion of how their blood system could be expanded. The meeting was well attended by a good cross section of the hospital professions and I was pleased to see that it had stimulated some thought among the staff.
The local Red Cross, who were considering expanding the blood service in Gizo have also asked for a copy of my report, which I hope they will find informative.
Overall I feel I have learned much from the experience of this project, not only in terms of the details of various blood systems, but also regarding the barriers to change that can be encountered. I feel that many of the things I have learned will be transferable not only to other developing nations, but also to the UK.
Thalassemia is the most common genetic disease in Sri Lanka. There are approximately 4,500 patients currently diagnosed, with around 80 patients diagnosed each year. Hemal’s Thalassemia is the only adult thalassaemia unit in Sri Lanka addressing the disease's complexities in adult patients, particularly the psychosocial impact such a diagnosis brings, and the challenges surrounding the treatment.
I spent eight weeks based at the Unit and North Colombo Teaching Hospital (a large government teaching hospital attached to the University of Kelaniya Medical School). This involved working alongside the doctors and staff at the unit, talking to patients about their experiences, attending clinics, assisting with local screening programs, learning about the diagnostic methods (HPLC) with laboratory experience and completing an audit evaluating the frequency of adverse blood transfusion reactions and extended phenotyping of red cell antibodies.
In addition, I also spent time at the hospital blood bank gaining an insight into transfusion medicine, and how it differs between Sri Lanka and the UK. Further, I worked alongside final year medical students and doctors on the acute medical wards, which was an eye-opening experience that further highlighted the differences between the British and Sri Lankan healthcare systems.
A number of learning outcomes were achieved over the two months based at the unit and hospital, which I hope will enrich my future practice as I start as a foundation year one doctor.
Student Elective Learning Outcomes Achieved
1. An insight into thalassaemia and the genotypes types most prevalent in Sri Lanka. It was an opportunity to learn about the challenges in counseling families about the implications of being given a diagnosis, and potential issues surrounding diagnosis of thalassaemia trait.
2. An understanding of the different thalassaemia genotypes and structural variants – particularly the variability in clinical presentation, and the challenges this brings to the management β Thalassemia intermedia and HbE β Thalassemia (for which there is huge variability in clinical phenotype). It highlighted the importance of managing the whole patient and theirs (and their families’) expectations.
3. Clinical skill practice – particularly cannulation and venepuncture. I assisted with a local screening programme run by the unit at a nearby government clothing factory, which involved taking over 150 samples of blood (see photos below) and with taking bloods/ inserting cannulas for patients’ at the unit.
4. Laboratory experience and an understanding of the techniques used in the diagnosis of thalassaemia using HPLC.
5. Completion of an audit looking at the frequency of adverse blood transfusion reactions and the extended phenotyping for red cell alloimmunisation performed at the local blood bank. This was challenging with often patchy documentation and lack of antibody work ups due to limited resources; but was a chance to learn more about red cell allo-immunisation and the differences in transfusion medicine in the Sri Lanka compared to the UK. It was also an opportunity to read through patients’ notes, and gain an understanding of the multidisciplinary approach to patient management.
6. In addition to time spent at the unit, the acute medical wards were an opportunity to further develop my clinical skills, with an emphasis on history (particularly where language barriers existed) and examination. Many patients were happy to be examined, which meant eliciting signs not commonly encountered in the UK (e.g. epitrochlear lymphadenopathy in a patient with suspected haemolytic anaemia and gross splenomegaly in a patient with suspected myelodysplastic syndrome). With patients often presenting at a much later stage, it was an eye opening insight into some of the socio-cultural factors influencing health care in Sri Lanka.
April – May 2015
Photos taken from one of the screening programs attended at a local government clothing print factory with approximately 150 workers screened
It is with pleasure that I write this letter to thank you for kindly awarding me with a £600 Travel Grant to attend the 20th European Hematology Association (Vienna, Austria).
First of all, I would like to emphasise how well organised the conference was and how it met my expectations in terms of scientific talks, networking and career workshops.
On the second day of the conference, I gave my presentation entitled 'The role of 2-oxoglutarate dependent dioxygenases in normal haematopoiesis and acute myeloid leukaemia' that was part of the Molecular pathogenesis of AML session. It went very well and I was asked good questions that worked as great suggestions for my next experiments. I believe that my project truly benefited from this experience, not only because of the questions I was asked but also because of the people I interacted with after my talk.
There were very interesting talks about epigenetics in AML, a hot field in leukaemia research that meets the aim of my project. T Milne (Oxford) presented his work about MLL fusions and how Chip-seq can help find new targets of the MLL complex. M Milsom (Heidelberg) talked about his team’s most recent paper (Nature, 549, April 2015) that links DNA damage and quiescence (the group used a fanconi anemia mouse model for this purpose) and J Zuber (Vienna) that gave an excellent talk about bromodomain protein inhibitors and MLL-AF9 leukemias by using an interesting technique called shRNAmir screening.
A number of molecular/biological/clinical topics were covered: ageing, stem cell niche, new therapies in AML, MDS and ALL amongst others. In particular, I attended a remarkably scientific working group session in which some of the best European groups working in stem cells presented their most recent work and gave some important information about novel approaches to characterise and understand the biology and regulation of hematopoietic stem cells. Amongst these, G de Haan’s work about tracking HSCs via bar coding during the ageing process was very impressive and inspiring.
Overall, I have a very positive feeling about attending this conference. It is already impacting on my research and it will certainly impact on my future career in science. I cannot thank you enough for this opportunity.