Wow... Interesting Case of Leukaemia

The twins who unlocked the secrets of leukaemia

British girls are behind dramatic breakthrough in medicine

By Steve Connor, Science Editor

Published: 18 January 2008

A study of two identical twin girls has led to a new understanding of the causes of childhood leukaemia and could revolutionise the treatment – and possibly prevention – of the potentially lethal disease. The detailed investigation of the two British girls has, for the first time, enabled medical researchers to track down the source of the cancerous stem cells in the blood that can lead to leukaemia in the first few years of life.

Olivia and Isabella Murphy, aged four, from Bromley in Kent, have provided science with an astonishing insight into the nature of leukaemia because of the highly unusual situation where both of them are at risk of the disease but only Olivia developed it.

Scientists believe the findings will enable them to develop better treatments with fewer and less serious side effects. It could also help in the search for the ultimate cause of the condition, which is newly diagnosed in 500 children each year in Britain.

Olivia and Isabella share the same genetic mutation to the blood-forming cells of the bone marrow, which must have occurred during their time in the womb because neither of their parents was found to have the same mutation.

However, only Olivia went on to develop leukaemia because she was unfortunate enough to have suffered a second mutation after birth, which triggered the onset of the cancer.

Scientists believe the mutation in the womb – which occurred in one of the foetuses but was passed to the other via circulating blood cells – caused both girls to be born with pre-cancerous stem cells in their blood, which predisposed them to leukaemia.

However, Olivia suffered the critical second mutation after the twins were born. That led to the development of the full-blown blood cancer which had to be treated with chemotherapy drugs that stunted her growth and led to a serious eye infection.

It was that difference between the two girls that enabled the scientists to locate the pre-cancerous stem cells in both children and then to figure out the sequence of genetic mutations.

Isolating the pre-cancerous stem cells from Olivia and Isabella, who will be five next month, could prove pivotal in the further understanding and treatment of childhood leukaemia, said Professor Mel Greaves of the Institute of Cancer Research in Sutton, Surrey.

"We suspect that these cells can escape conventional chemotherapy and cause relapse during or after treatment. These are the cells that dictate disease course and provide the bull's eye to target with new therapies," he said.

Olivia has successfully undergone treatment for leukaemia and is in remission. However, she is blind in one eye caused by an infection after her time on chemotherapy, which affected her immune system.

Her mother, Sarah, 35, said Olivia's treatment had affected her growth and her hair had become curly, but it had at least cleared many of the pre-cancerous blood cells identified by the research team.

She said she was worried about Isabella."Olivia is almost clear but ... Isabella still has a long way to go. They said the cells might die off naturally but obviously it is something which is hanging over us," Mrs Murphy said.

"It is quite hard but we have always tried to remain positive, although that is easy to say. It would be very hard to have to get through it twice but we are trying not to think about it too much."

Professor Greaves, whose study with Professor Tariq Enver of the Medical Research Council's Weatherall Institute for Molecular Medicine at Oxford University is published in the journal Science, said the genetic mutation found in the pre-cancerous stem cells of the twins was caused by the merging of two genes known as TEL and AML-1.

When the scientists inserted the hybrid TEL-AML-1 gene into human umbilical cord cells and inserted those mutated cells into mice, the mutated cells became self-renewing with the animals' bone marrow, just like they are in children such as Olivia and Isabella.

"This research means we can now test whether the treatment of acute lymphoblastic leukaemia in children can be correlated with either the disappearance or persistence of the leukaemia stem cells," said Professor Enver of Oxford University. "Our next goal is to target both the pre-leukaemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukaemia while avoiding the debilitating and often harmful side effects of current treatments."

Bruce Morland, a childhood cancer specialist at Birmingham Children's Hospital, said the study brought scientists one step closer to the "holy grail" of identifying leukaemic stem cells.

"By determining the characteristics of the leukaemic stem cells it is ultimately the hope of clinicians that therapies can be specifically targeted to the leukaemia, thus sparing the patient from some of the significant side effects of conventional chemotherapy treatment," he said.

Most common childhood cancer

500 new cases of childhood leukaemia in UK per year

1 in 3 of all cancer cases among children is leukaemia

50 percentage of all cases affecting under-five age group

80% survival rate of commonest form (acute lymphoblastic leukaemia)

55% cure rate for acute myeloid leukaemia (which accounts for 1 in 4 cases)

1 in 10 survival rate in the 1960s

0 survival rate pre-1960s

1.4% rise in in childhood lymphoid leukaemia cases in Europe from 1970 to 1999

45.6 per million number of cases among black children in the US during the 1980s and 1990s

27.8 per million number of cases among white children in the same period

50 per million number of cases among Hispanics living in California

~The Independent, UK~

Foreign

Strange how the thing I'm frightened most of is myself. What I'm capable of. And the things I don't understand. And don't know. And in the stillness of the night I lie awake and wonder. If I'm a fool, or if I'm a coward. My gut clenches in fear and my heart pounds. It pounds so hard I wonder if my ribcage would burst open with the pressure.

Fear. It's a foreign vocabulary. This is foreign territory. And I'm a foreigner here.

The insecurities come doubling back. And I'm bent double from the onslaught. Merciless. Unstoppable. Sudden. With no room for weakness. No room to catch a breath. And I know not how to fight back. How to stop this.

Fear. It's a foreign vocabulary. This is foreign territory. And I'm a foreigner here. In a foreign land.

Foreign.

Pacemaker

Thursday, 25.10.2007. 2151 hours.

My aunt is going on the pacemaker tomorrow. She fainted and her heart just stopped beating.

When mami called and I spoke to her, she sounded so different. So weak. So frail. So unlike the woman I so vividly remembered from my youth.

She was so vivacious, so energetic. Always so full of vitality, spirit. She always looked and acted way younger than her 62 years. Even last month, when I spoke to her, she still had that spark. That laughter in her voice.

How different that now she sounded like she was at death's door already, and I felt so lost for words. How to comfort her? How to make her smile? Her husband passed away when I was 18 from kidney failure. Her youngest boy is only a year older than I. She worries about him still. What can I say to make her feel better?

Here is a woman of strength, who still managed to build a substantially successful business and send her 3 children to Australia on a Form 3 education, who became Lion's Club President in a male-dominated small town.

Who stood up for her daughter when she felt her daughter was being put down, and she needed her. Who put up with me when I visited my grandmother alone.

I feel bereft already. Mami always did say I was more like her sister than I was like her. Rooster women, she said. Rooster women were strong. Rooster women were ambitious. Rooster women had fire. Rooster women don't give up.

I sure hope so. I pray to God that's true. She's too young. Not like this anyway. Not like this.

Fertility

the reasons i'm pasting these articles up is because The Independent archives their articles after awhile. and i want this for my own reference :P

but anyway, i remember some people asking about IVF and infertility treatments, so well, so i thought this would be easy reference.

it's so hard to get pregnant sometimes. i remember a former colleague of mine go through hell just to get a baby :( it's sad.

i have mixed feelings about all these new technologies, IVF, ICSI, and now this. i remember doing an attachment at a fertility clinic and seeing a woman who was 36 weeks pregnant coming in for a follow-up scan. 2 more weeks, and the baby would be ready for delivery. but the baby came up with bilateral pleural effusion and its complications (compression on the heart, etc.) the gynae performed a shunt immediately, but the baby died a few days later anyway. yeah, the baby was a result of infertility treatment.

being out of the medical line now, i guess i forget how fragile humanity can sometimes be. and yet, in the medical line, facing death and decay everyday, sometimes you get desensitized to it. just another body. just another death. how does one strike a balance sometimes?

***

A cheap, painless alternative to IVF?

Breakthrough in fertility treatment as first British babies are born using new technique

By Jeremy Laurance, Health Editor

Published: 25 October 2007

A landmark in the development of fertility treatment was announced by doctors yesterday with the birth of the first babies to be conceived using a revolutionary technique that offers a safer, cheaper alternative to IVF.

The twin boy and girl, who were born on 18 October at the Radcliffe Infirmary in Oxford, were conceived using In Vitro Maturation (IVM), a method that dispenses with the use of costly fertility drugs, saving up to £1,500 on the normal price of treatment.

The technique is also safer for the one in three women among those seeking fertility treatment who have polycystic ovaries, a condition that puts them at high risk of dangerous side effects from fertility drugs.

Specialists said the development could make in vitro techniques available to more infertile couples by cutting the cost of treatment. Infertility is estimated to affect one in six couples in the UK but IVF costs around £5,000 a cycle and treatment is restricted on the NHS.

Tim Child, a consultant gynaecologist at the Oxford Fertility Clinic and senior fellow in reproductive medicine at Oxford University, who led the work, said: "I think it is a safer, cheaper alternative to IVF for all women. However, for many women the success rates are currently much lower. Research in the future will address this."

The Oxford Fertility Clinic is the only one in the UK licensed to use the technique: 20 cycles of treatment have been carried out and four other women are currently pregnant, giving a pregnancy rate of 25 per cent. This is expected to improve with further experience. In addition, without the need for drugs, repeating the procedure would be less taxing on the woman. For standard IVF, the Oxford clinic's pregnancy rate is 45 per cent.

The parents of the babies, who have asked to remain anonymous, were delighted, Mr Child said. At birth the boy, born first, weighed 6lb 11oz and the girl weighed 5lb 14oz. "The parents are ecstatic. They have got absolutely stunning twins. They went home on Tuesday to start their new life together. It is wonderful."

In standard IVF, the woman takes fertility drugs for five weeks to stimulate production of her eggs, which are then collected direct from her ovaries under the guidance of ultrasound, before being fertilised in the laboratory. The drugs cost between £600 and £1,500, with charges often higher in London.

The procedure is time consuming and uncomfortable and for the third of women with polycystic ovaries there is a one in 10 risk of severe ovarian hyperstimulation syndrome, a dangerous side-effect that in rare cases can prove fatal.

IVM avoids the use of drugs and instead involves collecting eggs from the ovaries while they are still immature. The eggs are then grown in the laboratory for 24 to 48 hours before being fertilised and replaced in the womb.

Mr Child said: "The main advantage is improved safety for women. Women with polycystic ovaries have a one in 10 chance of severe ovarian hyperstimulation syndrome. IVM completely takes away that risk. IVF is also expensive. With IVM the cost is reduced, meaning it could become a more accessible form of fertility treatment."

The technique was pioneered by the University of McGill in Montreal, Canada, where Mr Child spent two years researching and developing it before joining the University of Oxford in 2004. It has also been used in Seoul, South Korea, and Scandinavia. To date about 400 babies have been born worldwide using IVM compared with around two million by IVF.

At present the Oxford Fertility Clinic is only offering the treatment to women with polycystic ovaries, but in the long term Mr Child said he hoped to offer the procedure to all women. "When we see patients we say these are the options and it is up to them to decide. We are not offering it to women with normal ovaries at present because we don't get enough eggs from them. It depends on the number of resting follicles and with normal ovaries you don't get so many.

"On average we get four eggs from a woman with normal ovaries compared with 16 from one with polycystic ovaries. The procedure involves a process of attrition – two-thirds mature and two-thirds of those fertilise – so you need a decent number to start with."

Research on developing the culture medium in which the eggs are matured in the laboratory could reduce the attrition rate so that fewer eggs are needed. The technique could then become suitable for women with normal ovaries, Mr Child said.

A second drawback of the procedure was that eggs grown in culture had a harder outer shell than those matured in the ovary and were more difficult for sperm to penetrate. The eggs had to be fertilised by ICSI – injecting a single sperm directly into the egg. "We hope to develop the culture medium so the egg doesn't mind being grown in the laboratory and we can use ordinary insemination [mixing eggs and sperm so fertilisation occurs naturally]. But in most IVF clinics, 50 per cent of patients are treated with ICSI anyway," he said.

A spokesman for the Human Fertilisation and Embryology Authority said IVF was expensive for most couples and a minority got treatment on the NHS. But it was too soon to tell whether IVM would replace IVF.

"Anything that reduces the cost of IVF, provided it is safe, means treatment could be available to more people. But this is an emerging technology – it is very early days. The most important thing is that patients get proper information so that they can make a decision on what is best for themselves."

~The Independent, 25 October 2007 14:11~

A revolution in the making - now it's up to the scientists

By Jeremy Laurance, Health Editor

Published: 25 October 2007

Over the past 25 years around two million babies have been born by IVF around the world. Yet the technique has always suffered from a major drawback – it meant dosing the woman with powerful drugs to stimulate her ovaries to produce extra eggs.

No one wants to be pounding their body with powerful drugs. It is uncomfortable, time consuming and costly, as well as dangerous for women with polycystic ovaries – one in three of those in fertility treatment.

If there is a safe way of avoiding the drugs but which achieves the same results, it would be welcomed by thousands of women. It is too soon to declare In-Vitro Maturation (IVM) the answer to their prayers. But it is a significant step in the right direction.

Avoiding the use of powerful drugs would bring a second important benefit – reducing the cost of treatment by at least 20 per cent off the average price of £5,000 per cycle. Cost is a major barrier for thousands of infertile couples denied treatment on the NHS – they cannot afford to go private and lose the chance to have a family.

The major shortcoming with IVM is its low success rate. A 25 per cent pregnancy rate will not be enough to attract most couples, although on a total of just 20 cycles it is a near-meaningless figure. Compared with IVF success rates of 45 per cent and more, it is a powerful disincentive, even if the risks are lower. But these are early days. When IVF first became widely available in the 1980s, live birth rates were around 14 per cent. They have grown from there and the expectation is that IVM success rates will grow similarly.

Specialists were cautious yesterday about IVM's prospects, saying much more evidence of its safety was needed. As part of its horizon-scanning work, the Human Fertilisation and Embryology Authority has been scrutinising the research in Montreal and Seoul, the two centres that have pioneered the technique, since early 2006.

Its advisory group concluded there was no evidence to suggest it was dangerous and no evidence that it increased the risk of birth abnormalities – a concern because of the use of immature eggs. But it warned that the oldest children conceived by the technique were little more than toddlers and long-term experience was lacking.

The HFEA granted a licence to perform IVM to the Oxford Fertility Clinic in January this year, the first and only licence it has so far issued, on the grounds that Tim Child, the consultant, had spent two years researching the technique in Montreal. He had demonstrated he was skilled in maturing the eggs in the laboratory.

The test now is whether he can refine the technique to improve the success rate – and whether other clinics can follow his lead. Researchers in Leeds are understood to be interested in the method. If he and they succeed, they could usher in a revolution in fertility treatment.

~The Independent, 25 October 2007 17:12~

LoL. Things I miss :P

{"I will tolerate no phones ringing. If you have your cell phone, please, give yourselves a cheap thrill and set it to vibrate."
-- beginning her first lecture.

"Some of you may have heard from less-than-pleased ex-students of mine that Professor Stanley is obsessed with sex. *pause for effect* This is true."
-- introduction to her first lecture (Tumour Biology of all things. But she did describe the reproduction of her lab mice in excruciating projectile-vomit-causing detail.)

"Hypertrophy is a response to excessive or prolonged demand, such as in the pregnant uterus - they don't call it labour for nothing."

"Semen is a most dangerous substance. Always avoid it at all costs. Research has shown that it gives you the biggest tumour of all - pregnancy."
-- explaining how squamous metaplasia is caused in the uterus.

"Some of these names are very old - we've used them since pussy was a cat."
-- introducing the terms 'melanoma' and 'seminoma'."

"Normal tissue is ordered and structured, like the dancers in Strictly Come Dancing. Cancerous tissue, then, is like the Strictly Come Dancing afterparty."
-- quite self-explanatory really.

"Bitter experience has taught me that 80% of this lecture theatre will not know what 'faecal' means, and that I must use language appropriate to your generation - this, ladies and gentlemen, is shit."

And they say med school lecturers are boring.}

-excerpt from Angry Medic. :P HAHAHAHAHAHA!!! that's from Cambridge, btw.

sometimes i miss what i studied. O&G docs are chockful of dirty jokes, especially.

i said this once, i shall say it again: Nothing is sacred in the medical profession!