Ural doctors, researchers have created a technological system to help children with cancer. As a result, mortality in the Sverdlovsk region has become one of the lowest in the Russian Federation
Larissa Fechina "I our clinic rightfully ready to call the scientific and practical center"
In Larissa Fechina tenacious doctor look at it — a good radiant eyes. In face, manners shine through stress and anxiety profession, although she hides them for doctoral correctness. Every day, she is forced to look into the eyes of the parents of terminally ill children and inspire professional exploits of his team.
The idea to treat leukemia in infants by reprogramming tumor cells now come to the honored doctor of the Russian Federation, deputy chief physician of the regional children’s hospital number 1 on oncology and hematology (Yekaterinburg) Larissa Fechina in 2003. In 2006, a team of researchers under the leadership of its proposed new method for Russian colleagues. The global medical community valued domestic know-how in 2009. For the treatment of infant leukemia Center of Pediatric Hematology and Oncology in Yekaterinburg has the best results in the world.
— Larissa G., a Center of Pediatric Hematology and Oncology, and enter something terrible: painful to look at these children and their parents … How to work here?
— Job offers for us: people — the first question for me. Of course, the team did not appear immediately. In 1985, I first crossed the threshold of a children’s hospital and was planning to work an infectious disease. In my stock character to get fast and good results to treat the child a week — he was on his feet, and everyone is happy. But I came at a time when the children’s hematology department went all the doctors. At the time, worked here for five or six years old and going. Suffered from a psychological syndrome of burnout, job fatigue: they could no longer see the loss of children, the suffering of the parents.
Here then there was only one trained doctor — Olga Popova, and she was in the hospital with severe viral hepatitis. And three young girls and doctor were to somehow treat dying children, talk to their parents … We were under the hospital window, where lay our mentor, and shouted: "Olga, here’s this baby receives up tomorrow to appoint? .. And that? ‘. So it was, I swear! And not long ago, only 26 years ago.
For three months I came home and cried. I’m from a family physician, medical dynasty. My father was strict: "Can not — go away." But I could not get away from the ruins. And then we were lucky in the early 90’s borders were opened in Russia came to public charity Care-Deutschland (in translation — care). The Germans decided not to help food rations and improve what was the worst in our medicine. Pediatric oncologists country gathered at an international symposium in Minsk. First impression — the imperialists are lying, telling about some unattainable results. We were dying eight out of ten children, and they had a reverse proportion. They said that the success of treatment in high-quality diagnosis, but her at that time in Russia was not. And in a very intensive cancer treatment, but it seemed to us that it will not transfer patients because of the high toxicity.
In autumn 1992 we were visited by the famous German pediatric oncologist Fritz Lampert. Looked at our antediluvian monocular microscope and was surprised: "I can not see!". It was a time of empty shelves in Russia, soap coupons, problems with medications. And the next time a professor came to the king’s gift — a microscope Carl Zeiss. And in May 1993, I, the newly made zavotdeleniem (to me then was not yet thirty), together with a very young colleague was invited to Germany to the University Hospital of Giessen in the four-month study. In the usual children’s hospital, but with cytogenetic and molecular biological laboratories, computer tomography, nuclear medicine departments, which have only recently begun to develop. We see there that our profession in the world is very high and requires a good diagnosis, completely absent in Russia. That is, we realize that we have nothing to treat.
From Germany, I went with the intention to create such laboratories, sending young professionals to study abroad — German organization took care of all the expenses. Then assistance program ended. At the suggestion of Lampert, we held a charity bike ride in Yekaterinburg, collected tens of thousands of German marks. They opened with the money first cytogenetic laboratory. We wanted to develop the technology to move forward. In the darkness is not rushed — in Germany and other countries have seen how and what to do. After studying in Germany, Europe and the United States, many of my colleagues.
Try — SUCCEED
— How do you develop?
— Began cytogenetic studies have become more deeply understand the biology of the tumor. Due to this we have the courage to make decisions and implement protocols — standard for Germany, but unusually intense for a national children’s oncology. Protocol — it finished work on the study of a particular disease. It chronology of world experience of treatment, the analysis of the effectiveness of the previous results, the rationale for the program directly regimens, drug delivery, all the possible complications, participation clinics, and more. Such protocols can only be cooperative: doctors, researchers need to check his watch.
Then, gaining practical experience in treating patients in the well-known international protocols, we saw that in the world there are diseases with a less successful outcome. For example, the treatment of leukemia in children in the first year of life. We managed to create a custom protocol MLL-Baby: the title of the gene that determines the unique biological properties of infant leukemia — Mixed Lineage Leukemia Gene. The poor results of treatment were the result of an incredibly wide variety of gene rearrangements in cooperation with numerous options of its partner genes. We got the first positive experience of treatment and see what the next version of the protocol had to improve it. The protocol has brought us fame both at home and abroad before the infant leukemias are very poorly respond to treatment.
— Where does this matter?
— This is a mistake of the genetic code. The cells within our body divide and differentiate (become more mature) every hundredth of a second. The body inevitably wrong, but the immune system recognizes the cells are normal in a compromised and ruthlessly destroys them. In young children, the immune system is not yet mature, plus there are antecedents of trouble. When the immune system loses control over the processes of cell division and maturation, the conditions for preferential survival of progenitor cells of the tumor clone. And further includes a mechanism for tumor progression. The disease can be detected when the number of tumor cells is 10 to the 12th power. Tumor development occurs rapidly, so that the child, when he is diagnosed, the tumor has a catastrophic volume, about 1 kg of weight, and a huge number of white blood cells — more than 100 000 (normal 6 — 8000). And most importantly, 80% of infants unfavorable adjustment in the MLL gene does not allow high-quality cure leukemia.
For a time, the tumor with chemotherapy can be suppressed, and then it comes back. In the world of doctors tried to increase the intens
ity of chemotherapy — it did not help: the children died of toxic complications, and if survived and achieved remission, not for long. Tried a bone marrow transplant — did not help either. Noticed the biological similarity of acute lymphoblastic leukemia with myeloid. In Europe and the U.S. as part of a large multicenter study of treatment of infant leukemia decided to use drugs that are effective in Myeloid, but it has not brought the desired results.
And in 2003, we had the idea that since these leukemias occur in infants of very primitive cells, and the MLL gene is involved in the differentiation block, this block is necessary to somehow remove. We decided to include a drug therapy that is able to do it. He called ATRA (the initial letters All Trans Retinoic Acid — fully transretinoevaya acid) and is used to treat leukemia older. We added it to standard chemotherapy and received an unexpectedly good result in a child who has not had a chance. We thought it an accident. Tried a few more times — and again turned out. Realized that it seems to be a tool that is directly involved in the reprogramming of tumor cells and sends a different way of differentiation and development. After a few successes with our patients in 2006, we offered our Russian colleagues report. Now that the Russian-Belarusian research MLL-Baby 24 participating clinics. And the medical community valued domestic know-how only in 2009.
— Why are you late?
— We had to make sure that the long-term remission is achieved, and the criterion here — the five-year survival rate. After this period, relapses are rare. When we saw that the children since 2003, continue to be in high-quality long-term remission, feel good, there are no more cancer cells, as no cells with MLL gene rearrangement, and then told it to the country and the world at various conferences, congresses . Including in America in 2007 at the World Congress, organized by the American Society of Hematology. Although none of us at that time was not part of this society, I sent the invitation to speak, and then took a full member of society — for performance.
— Why do you share it with foreign counterparts?
— First in the world to have had successful solutions. Secondly, doctors differ from entrepreneurs that are interested to tell colleagues about what they do. Simply inhumane to delay this information from you. It offers families with sick children, not only in Russia: the letters come from Bulgaria, Germany, Ukraine. Experts from other countries helped us free. And now we take the study physicians, pass this baton. In our profession, all the brothers in spirit, we are in the world a little bit.
— Why you have not issued a patent?
— And what did he give you? That this is our know-how in the world knows. Our requests for speeches and publications with the current results of our protocol is always with great care taken in the international markets. This year we were in Munich at the international conference "Leukemia XIII" in London at the Congress of the European Hematology Association, three works made at the Congress of the United States. In the world recognize our priorities.
CENTER IS NOT REGISTER
— Why it took to create a Center for Hematology and Oncology at Children’s Hospital in?
— By 2006, it became apparent that not all of the technology we will be able to apply. There was not enough of an important section: bone marrow transplantation. To implement this method of treatment, it was necessary to re-equip all. We asked the then Governor of Sverdlovsk Region Eduard Rossel to reconstruct the two boxes to make two sterile rooms for transplantation. He took the decision to build a new large-scale housing. And here to introduce the most advanced thing in the world. Sverdlovsk region of the project has risen to budget money — donations of large companies. We have no desire to hang a crystal chandelier over golden toilet. We chased the adaptability and functionality. The German general contractor Transumed Medizintechnik GMBH always kept a dialogue with us.
In late 2006, we have successfully carried out the first transplant. Now reached the most complicated type of transplants — from disparate but related donors (mom or dad), where a specially modeled mechanisms of suppression of tumor cell donor. Thus, working on the tumor and have an interested donor. Because, unfortunately, in our country there is no national registry of bone marrow donors. We have to look at foreign registers. Colleagues wonder, why in Russia there is no donor registries. First there were only the beginnings — in Chelyabinsk. In Russia, much still on the enthusiasm. There are the first cord blood banks: in Samara, Moscow (Tsarina). We did the first transplant of umbilical cord blood of 10-month-old girl from the north of the Tyumen region, and suitable for her blood found in the Samara bank. I’d love to appear in the bank and the Sverdlovsk region.
— People who come into the team — are scientists, medical practitioners?
— All in one tube — doctors, scientists dash. The development center is based on a very close cooperation of the world of professional teams. Science is coming from the bedside: a child, a tumor which is not yet possible to cure. And there are the first ideas. My job is to make sure that our young people entered into co-operation with colleagues from other countries. We have a year of specialist works and goes to watch the best laboratories in the world. Some team members are part of a group of international experts, they are invited to the expert site of our European partners. Alexander Popov went to Italy for a meeting of the advisory council on flow cytometry. Alexander Druj now in New Zealand, makes a report to the International Congress of Pediatric Oncology. He graduated from the Urals State Medical Academy in 2010, the winner of the contest of young scientists, was awarded the Governor’s Award for the paper "Molecular markers of neuroblastoma metastases to bone marrow." Seems to be a small amount, 100000, it will not do serious science. But the guys realized that the country needed.
In the world today we are not just seen as experts, but are willing to act on the name is the most respected venues. We have attracted international attention. We need to meet: to raise the level of experimental medicine.
— In the Kremlin when awarding grants you mention of the …
— About the research projects in which grants would be for young people. We need funds for sophisticated experimental studies confirming our scientific hypotheses that are clinically already taken place: we saw the results in patients. So does the whole world confirms the clinical effect in the experiment. Then no one has any doubt, why and how it works. And our clinical benefits based on scientific hypotheses. Here Russia swung Now Skolkovo. But science is developing not only in Moscow. I our clinic rightfully ready to call the scientific and practical center. We should be able to develop further.
Time is now seeking funding to carry out very complex molecular studies on cell cultures using high-density microarray. Americans and Europeans support such activities by state grants. And we are still at the level of all the great desire of people who work in the clinic. It would be correct if the government turned its attention to the fundamental designs. We own life-saving technologies treatment of socially significant diseases. Finding effective methods for diagnosis and treatment of such diseases should be a priority for the country’s health.
— It does not happen in the center of the burn that you caught?
— Burnout is no more. First, technology came second r
esult. When you get a good result, it is neither an incomparable delight, you simply carries forward on the wings. The doctor is no longer left alone with the patient and their personal experiences about his condition. Every day, we discuss all the patients in the clinic, all ready to connect. We instantly solve the current problem: this further study, this advice with experts that will look for a donor. But anyway here is not easy. I have none of the 20 young did not go to the West. They’re like, but I’m not. I myself received such offers, for example, from the Japanese.
— Why are they coming back?
— Because here they realize their creative plans, and there will be working on the idea of someone else’s uncle.
"Every time limit and advancing wanted to say, well, everything, it’s time to do something else in life, there was something good that changes the situation. Now I’m not afraid: my business to pick up the team in any situation "
BEST IN THE WORLD
— What are your results in comparison with the world practice?
— On treatment of infant leukemia — is better. Number relapse does not exceed 25 — 30%, and in known clinical groups on the West — from 45% and above. The level of disease-free survival for us — 60%, there is — no more than 40%. This is what we are better thanks to an innovative method of treatment. In the Sverdlovsk region Cancer incidence among children is 15 cases per 100,000 per year, it is comparable to that in the West.
However, we are seeing an increase of cancer incidence from year to year. The health of mothers — a complex issue, plus the so-called "random" genetic rearrangements. Deaths from childhood cancer in the Sverdlovsk region is among the lowest in the Russian Federation — 3.9 people per 100,000 child population through a centralized system of care in the region, this model was created in our recent years.
It is important to physicians in other non-core hospitals in time to suspect the tumor and send a child to us. We are doing everything necessary. The first — establish an accurate diagnosis of the tumor. It uses a range of techniques: modern imaging techniques, computed tomography and magnetic resonance, research in gamma-camera and ultrasonic devices for ultrasound expert level. Next — a detailed study of the biological nature of the tumor. Climbs the tumor site, put morphological diagnosis, conducted molecular biological and immuno-histochemical studies on the presence of genetic abnormalities. We study the chromosomal breakage is searched disorders of the immune system. All this is complicated and costly procedures that are performed under the roof of a hospital. This is the key to success, because at a time is a lot of research to make an accurate diagnosis. And further still need to check how the treatment will be effective. Here, we use a very thin immunological and molecular techniques in order to catch one tumor cell per 100 thousand, a million. Depending on the level of minimal residual disease, we can intensify treatment or reduce it to keep the swelling under control. There are tools and knowledge that will allow you to do.
Upon completion of the treatment time in three months, six months and a year kids come to us for inspection. We are responsible for the outcome of treatment, patients have not lost in space and time. Constantly working day hospital and outpatient care. We work on good European level. But all the time there is something new and very important, which can not be missed. For example, I look with great hope for the development of nuclear medicine in the Urals recently put in Urfa cyclotron.
— What would you want from her?
— Looking for short-lived radioactive isotopes of iodine. They were not taken to transport the Urals no transport company. We were brought in for technetium bone scan, while the half-life metayodbenzilguanidina so small that it is impossible to bring. There are patients who need to conduct research with radioisotopes of iodine to search for metastatic neuroblastoma — the most common childhood cancer, after leukemia. Imagine the absurdity: instead of spending study here, we send them to Moscow.
We unconditional but leave the initiative in our nuclear scientists: there are technologies that are very much in demand childhood cancer centers. I just talked to you about the diagnosis of neuroblastoma isotopes of iodine, and there is treatment to, this method is not applicable in Russia in general, patients are forced to travel to the West. It is necessary to create a nuclear medicine clinic, which would not only isotopes for medical treatment, but also the special conditions for the deployment of the child, parents, recycling of waste. When creating a federal center in Moscow this technology for some reason have not tried. Maybe Yekaterinburg, where the center will be open nuclear medicine, will be on the front lines. In the Urals, the correct trends, they should be actively promoted.
Give kids a chance
— You kids are just out of the region?
— No. But patients come by all means. Terribly unfair: inoregionalam to get here, we must find a charitable organization. Although our base is willing to accept, we have both the desire and ability to help. The question in the notorious state order. Our clinic is needed to provide the federal government orders a high-tech medical care to children from other regions. We have a government order for the Sverdlovsk region, which is co-financed by three-quarters — of federal funds, the quarter — the regional budget.
— How much is the treatment?
— On average, about 10 to 15 thousand dollars. The state allocates one hospitalization 109 thousand rubles for co-financing. A child from another region can not be treated here, on equal terms, because his region is not involved in the process of co-financing. The budgets of a number of areas such money. But then assistance can be provided here, at home. Just need a model in which the clinic is officially could send patients for treatment with us.
— Who can make a difference?
— I personally appealed to the Minister of Health and Social Development Tatyana Golikova.