Beryl Thyer

Memorial Africa Trust

Burkitt's Lymphoma: Research

Research is necessary in medicine. It leads to a better understanding of disease processes, it may indeed provide the cause of diseases. It may thus lead to more appropriate treatment of diseases. It may even lead to the prevention of diseases. This of course is better than the cure of diseases. Dr Burkitt once remarked that if you want to manage the problem of people falling over cliff-tops, it would be wiser to put a fence along the cliff-top than a fleet of well-equipped ambulances at the foot of it.

Research on infants and children poses specific problems not generally applicable to research in adults. The question of permission is supreme. A child is not usually able to comprehend the issues being investigated and therefore not able to give informed consent and permission for the research project. It requires full explanation to the parent or guardian, and this may be at such a time as these adults are acutely distressed by the child's illness. The issue becomes even more acute when one considers research on the newborn; how do you realistically expect a woman in labour to absorb and understand the issues relating to the research you wish to perform on her newborn?

Much research requires invasive techniques, and we do not like to hurt children; parents don't like that either, and might reasonably refuse permission. It is understandably difficult to explain that one is not experimenting on the child.

There have been unfortunate outcomes for professionals and patients as a result of research entered into for the most rational and laudable reasons. As a result of this, there has developed a strict code of practice as to how research should be approached, especially where children are concerned. Ethics Committees and Institutional Review Boards hear all proposals. Permission to proceed will not be given until every possible avenue of enquiry and doubt has been fully explored, and every professional guideline followed.

This is very correct, and reassuring to medical researchers, and comforting to parents. It can go 'over the top' though, and I invite you to have a look at the following hilarious account from British Medical Journal 2004, which is a perfect illustration of how daft Ethics Committees can get:

When Dr Mopp tried to get into research

Initially, it had all seemed so easy and straightforward. Working in a large children's hospital, I thought it would be useful to survey paediatric nurses and doctors about their knowledge of popular children's television characters. Knowing one's Tweenies from one's Fimbles always helps in communicating with a wary preschool child, and it would be interesting to find out just how much paediatric healthcare professionals knew about these things. Filling out a little questionnaire would be a bit of fun for everyone involved. But fun and research don't always make easy friends, as I was soon to learn.

One of my colleagues wisely suggested that it would make sense to survey a few young hospitalised children as a control group. This sounded like good advice, but that's when the trouble started. In order to be able to ask a few children whether they recognised Tinky Winky or Jake, I was told I had to apply for approval from the ethics committee. In order to obtain this approval, I had to seek statistical advice. The statistician asked me to do a pilot study first to establish how many children would be needed for my project. Having done so, I finally filled out the rather lengthy ethical approval application form. After all this, I was told today that the form has changed as from this month to a new nationwide form.

If you never read this study written up in any journal don't be surprised. Mind you, I will add it to my portfolio as an extremely interesting learning experience in politically correct research.

Markus Hesseling, specialist registrar in paediatrics,

Alder Hey Children's Hospital, Liverpool

This Dr Hesseling by the way - though a senior Paediatrician in the biggest Children's hospital in Europe - is unrelated to Professor Peter Hesseling of Stellenbosch University, of whom you will read much in this site.

So what about research into BL in Cameroon? What is possible and what is impossible?

It would be very fine to know the cause of BL. A great deal is already known, a number of co-factors in the causation are agreed though the inter-relation of them is uncertain. The earliest research was by Denis Burkitt himself, and this you may have already read on this site. His research was non-invasive for his patients; he didn't stick needles in them or perform high-tech tests on samples; or have at his disposal a well-equipped laboratory. He asked himself what are the geographical limits of this disease? His great 'Tumour Tour' defined the area where BL occurs, and where it does not occur. This posed another question to Burkitt; 'why in this area, and not in that area?' Colleagues of Burkitt helped him out with that. Everything Burkitt achieved was due to his power to ask the right questions, and do something about it. His scientific approach was essentially epidemiological; recording his findings for others to interpret. His conclusions have stood the test of time.

Time and science moved on, and left Burkitt 'in the dust' as he himself said. Great discoveries in virology and genetics have superseded Burkitt's beautiful original research. Most of this modern research has been in Europe and the USA, and most of the patients to benefit from it are also from the developed world. Poor old Africa - where BL is the commonest childhood cancer by far - and where 80% of the world's cases of BL are - is being left behind. There are no virology or genetic research facilities in Cameroon. There is no money for them. Therefore further scientific research into the cause of BL in Cameroon is not possible. If it were possible it would require a substantial donation from a grant-making organization at home. By way of introducing a ray of hope, I can say that there is one science-orientated doctor of my recent acquaintance, who is actively seeking funds for BL research in the NW Province of Cameroon in 2006. Watch for updates in this site.

'Clustering'. The majority of BL cases admitted to BBH and MBH come from the area indicated by the pins on the map.

Clusters provoke questions; Why from here? Why not from elsewhere?

Quite apart from the pure science of causation, there is the opportunity for Clinical Research, and this we are conducting in our two centres - BBH and MBH. The underlying philosophy in our clinical research is based on the following facts:

BL is common in our area of activity

BL is lethal if not treated

BL is known to respond rapidly to chemotherapy

Simple chemotherapy has been used successfully since Burkitt's time.

Multiple chemotherapy for BL is very successful in the developed world

Multiple chemotherapy is not available to African cases of BL

Simple chemotherapy should be explored and exploited for maximum benefit

Our overall Director in the Trials we have undertaken in Cameroon is immensely experienced. Professor Peter Hesseling has been treating BL and other childhood cancers for many years. There are people surviving BL whom he has followed up from childhood to marriage, and was then involved in the management of one young man's sub-fertility which was probably the result of chemotherapy he had received in childhood. It was a pleasure and privilege to have been invited to collaborate with Professor Hesseling in his ongoing BL work in sub-Saharan Africa. It was my reward after 5 years of wondering and waiting; years of longing to get on with the treatment of children with BL but not knowing where to begin.

Ad hoc treatment regimes had hitherto been used at Banso Baptist Hospital (BBH); multiple chemo was used when available and if patients could afford it. Statistics as to how well we were doing were non-existent; patients regularly failed to re-attend for further therapy; follow-up and proper surveillance were non-existent. Pathology tests which would confirm the diagnosis were not done. I had previously been on the periphery of a BL Trial in Kumasi, Ghana. Multiple chemotherapy was used there. Their follow-up was not good, the results of their work were not encouraging. I was very happy to have the guidance of Professor Hesseling, and to become the co-ordinator in Cameroon of the BL work in which he was so deeply involved and so widely experienced.

It was now possible - in 2002 - to write down the basic ingredients for our own proposed clinical research:

Hospital Institutional Review Board (IRB) permission required

Treatment Protocol to be written

Patient Documentation books to be designed and made

Training in tissue sampling techniques to be accomplished

A Pathologist for analyzing the samples to be approached

A Research nurse assistant to be appointed

The necessary drugs to be acquired

Proper follow-up arrangements to be made

The development of a BL Registry to be started


Research Assistant Nurse Vera, Kumbo Hospital	Research Assistant Nurse Vivian, Bamenda Hospital

Easy to write down and exciting to contemplate, but not easy to get it all set up. Arranging a meeting with the IRB was very frustrating. Try mustering 12 African colleagues from hither and yon in the NW Province; see if you can settle on a date, let alone a time to meet! It was ages before this was achieved. The proceedings were useful though, for I was made aware of many points that I had not considered.

I had already written a Protocol; it needed revision in the light of the IRB recommendations. It was then accepted. All doctors involved in the research - including myself - had to learn (from Prof Hesseling) how to take samples from the patients' tumours. This is desirable for confirmation of one's clinical diagnosis, and necessary if one is ultimately to present one's results to colleagues around the world. We knew of a properly qualified Pathologist in Bamenda. He was approached and agreed to analyze our specimens.

The IRB pointed out that we would need a specially trained nurse to do much of the pre-treatment management; the explanation to parents; the consent to proceed in the Trial etc. BBH Administration wasted no time in appointing such a nurse. The doctor on BBH Children's ward was happy to enter into a well-managed BL Trial. The Chief Medical Officer and the Hospital Director were supportive of our plans.

The acquiring of the necessary drugs - cyclophosphamide (CPM) and methotrexate (MTX) - was from the beginning a problem. We knew that parents were in general unable to afford even the simple chemotherapy we were planning. From the outset Professor Hesseling received assistance from the Lisa Thaxter Trust, and from the beginning the Beryl Thyer Memorial Africa Fund has been used for this purpose. We were fortunate that the manufacturers of CPM continue to give generous donations of their product, and that the manufacturers of MTX also donated on one occasion. Our joint efforts have resulted in children admitted with BL receiving their anti-cancer drugs free of charge. This a situation we would like to see continuing; so we continue to seek funds; we continue to research; we continue to rescue children; we continue to hope that the people of England - and perhaps beyond - will continue to enable us..

From early in my BL experience, I came to realize that follow-up was vital. A treated child lost to follow-up is also lost to statistical analysis; we are unaware if he is still alive; and if now deceased, we are also unaware whether the death was due to recurrence of the tumour or to some other disease. So it was that from the beginning of our scientific BL work, we have consistently stressed to parents that they must return for further chemo treatments on the dates we give them - even if they believe - as often they do, that since the tumour has now gone, the child is cured, and there is no further need to come to the hospital again. If they are unable to come we try to contact them in any way we can; we will know the child's school - perhaps we can speak to the headmaster. We will know the family's church - perhaps we can contact the Pastor. If all else fails we will go and visit them at home taking a photograph of the child and parent with us. This exercise is both time-consuming and expensive. The cost of home follow-up visits exceeds the cost of chemotherapy. It is my belief however, that if other workers in this field approached follow-up with the tenacity that we do, they would have better results than they do. Contact with treated patients needs to be maintained for one year after cessation of chemotherapy. If the child is well when seen at that time, a cure can be claimed, parents will be grateful, and the visiting team will be full of joy. We have been thus privileged on many occasions in the humble homes of remote bush communities. One-year follow-up figures round off the statistics for each child seen and treated. In this way a Cancer Register is automatically created; a matter of great importance in itself.

Let me quote here again - because it is so true and so poignant - the contribution of Aloysius to the follow-up of Dr Burkitt's cases:

Mr [Aloysius] Kisuule …probably speaks every language in Uganda. We sent him to find all the patients who hadn't reported back to the hospital - about eighty; and we knew this was a quite impossible task…Well, he found seventy-seven of them. We wanted … to find a boy who'd given his address as Msambya Hill, two miles outside Kampala. Aloysius couldn't find the boy there, so he simply sat down in a convenient spot, and whenever anybody passed he'd ask if they had seen a boy with a swollen jaw. After he'd sat there for a week a passer-by remembered the boy, and Aloyisius tracked him down to a place called Kimuli, ninety miles away. This is cancer research… This benefits humanity at large. 'The Long Safari' Bernard Glemser; 1971

Our own survival figures are as good as any in Africa and much better than some. About 70% show immediate and complete response to the treatment, with disappearance of the tumour by day15. Some cases relapse, so that the situation is less good at one year. However, between 50 - 60% of children are rescued from the disease, and can be expected to be long-term survivors. And we are glad!

To read about some of our own experiences in home visits, have a look at:

Burkitt's and The Motorbike

Burkitt's in Bamenda

Burkitt's Lymphoma ~ Domiciliary Visits

These experiences can be found in the 'Burkitt's: Follow up' page of this website.

(Burkitt's: Research)

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Beryl Thyer Memorial Africa Trust, a UK registered charity ~ 1112603