Bone marrow transplantation annually 3 thousand Russians. What is HLA-typing, why you need a bone marrow transplant, how dangerous it is and why it is so important the national register of bone marrow donors, told Mednovosti scientists of the Russian national research medical University named after N. And. Pirogov – winner of the national prize “Complicity” on the development of voluntary donorship of blood and its components.
In the Public chamber of the Russian Federation summed up the results of the VIII all-Russian award “Complicity” for contribution to development of donorship of blood. According to the Director of the National Fund of healthcare development, Deputy head of the coordination centre for blood donation at the public chamber Elena Stefanyuk, this year there were over 350 entries from 52 regions of Russia. Just awarded over 100 awards for achievements in the development of voluntary donorship of blood and its components. Among the winners and the prizes to the winners, and a creative children’s competition — institutions of blood Service and non-commercial organizations and initiative groups, representatives of business, government, media, blood donors, creative people of different professions and ages from more than 40 regions of Russia.
For the first time in the history of the Award one organization, the Russian national research medical University them. N. And. Pirogov – won in four categories. For the best project aimed at increasing the proportion of regular donors and the development of responsible donorship, the best scenario possible to replicate successful practices – the quest “Drop of life”,” video “does Not need to be a superhero to save lives,” and issues #Donart donation in the University and beyond.
And the University recently held a mass donor event, during which more than half of the participants were HLA-typing was included in the register of potential bone marrow donors. About the new direction the University donation campaign, and why it is so important HLA-typing and the national register of bone marrow donors, told Mednovosti Vice-rector on scientific work of the Russian national research medical University named after N. And. Pirogova d.b.N. Denis Rebrikov and head of Medical Department, head of donor movement University, Tigran Muradyan.
Transplantation “immune system”
Denis Vladimirovich, why the need for bone marrow transplantation?
Is a method of treatment of cancer of blood in which blood cells fail to carry out their functions and begin to multiply uncontrollably. The output from this situation one need to destroy such “asocial” cell. It’s possible, but then you have to actually destroy the entire immune system, because its form is also blood cells. The human body becomes vulnerable to many viruses and bacteria, and may die from infectious diseases. But if you do not restart the hematopoietic system, he will die from cancer. Therefore, today bone marrow transplantation is the only solution for many such patients. The biological material for transplantation is a blood stem cells from a donor.
What is a transplant?
Transplants are of two types: related and unrelated. Related material is taken from parents, siblings or even children (once they reach 18 years of age). The main disadvantage related transplantation is that only about half of important to transplant the genes of the histocompatibility of the donor and recipient are the same, and the second part – alien. And this from a medical point of view is a problem because when you transplant it is important that the body is not rejected by the recipient.
Consider this example: if transplanted to, say, a kidney, then she should fit the composition of the surface protein receptors, which the body operates a system of recognition of “friend or foe”. If these protein-receptor grafted on will not be similar to their own proteins of the recipient, the system “friend or foe” will consider new on the alien and starts the process of rejection. In this case, the immune system will attack the transplanted organ is exactly the same as, for example, bacteria that the body needs to expel. Therefore, prior to transplantation and checked these surface proteins-receptors, they are called genes histocompatibility complex or abbreviated as HLA. But if for organ transplants such as kidney, allowed a partial HLA match with the patient, in the case of bone marrow transplant and a match must be almost perfect.
In fact it is a transplant patient a new immune system, and if it proves to be unsuitable, the inside of the body will arise, figuratively speaking, cognitive dissonance. New immune system will perceive the recipient’s body as foreign, it will attack all the organs and tissues of a new host, develop lethal systemic inflammation, and the recipient will die. That’s why in the case of bone marrow transplantation requires careful selection of material. And for that living-related transplantation is not ideal, because in this case the bone marrow is a priori alien half. Of course, it’s better than nothing, but still the percentage of complications in the recipient is very high.
Therefore, the correct approach to the selection of material is in an unrelated transplant is selected from a huge database of donor matching perfectly. Of course, it happens that even in a large database of donors could not find a complete match, but only to 90-95%. But modern medicine offers a good method of immunosuppression that reduce the rate of complications.
For this, and a Register of potential donors?
– Of course. As practice shows, in most cases, you can find the perfect donor of about one million donor Register. And if the country has Register a million donors of bone marrow, any bone marrow transplant we can find for almost any recipient. Registers potential bone marrow donors have long existed in developed countries: USA, Europe. A particularly large registry in Germany: about 7 million people and growing. It is clear that such a gigantic register you can easily find the right particular recipient of the donors, send them suggestions, and it is likely that someone from the candidates agree to undergo the procedure of bone marrow.
In Russia, in the absence of the Register, the situation is as follows: Funds, collect donations, have to spend very large sums for the donor search abroad, and the fence of his transplant.
Plus self-Register in the fact that it will unite the people of our countries – closer genetically than the peoples of Europe. If the Germans are relatively close resident of Central Russia on the genetics, the genetics of the peoples of the Urals is quite different, and the probability of finding in the German registry for a suitable donor for, say, Uyghur, Tuvan or much less. From this point of view need in the country to create its register taking into account the genetic diversity of the population of Russia to the donor with the desired genotype can be find faster.
What is the procedure of collecting bone marrow and how it’s dangerous for the donor?
Modern medicine offers different ways of donating bone marrow. First the donor is under anesthesia, we take the bone marrow directly from the bone (usually from the pelvic) by means of puncture. Second – minimally invasive: material for transplantation taken from a vein, as in a regular blood donation, but before that, the donor receives a drug that “throws” the bone marrow cells into the bloodstream. During the procedure, needed cells a special machine sorts the directly from the blood flowing through it, and the rest of the blood is returned to the donor back.
In contrast to all other types of transplantation, bone marrow transplantation for the donor almost safe, because it gets a very small part of the bone marrow and the remaining cells is sufficient for life and quick recovery. The recipient’s new marrow is formed from a material that was transplanted into him, and he has a chance for a cure.
What is the technology of typing?
Genotyping – genotyping for HLA – today is carried out using a special high-throughput sequencing is very powerful device – sequencer, is able to simultaneously analyze the material, from 100 to 1000, determining the DNA sequence of each donor. A technological breakthrough in the field of determining human genotype occurred about 10 years ago, when the sequencers of second generation machines to determine the DNA sequence performance thousands of times more than the previous generation phones. It is not only about the devices themselves, but also reagents.
The more powerful a device, the cheaper is the cost of the unit of information. Because DNA is simply the carrier of information. If you write a complete sequence of the human genome on a simple flash drive, it takes about 3Gb. But this is the final assembled version of the genome, the raw information for analysis, received from a sequencer, it takes about 100 GB. Interestingly, even from the final 3 GB of a fully assembled genome of useful information just 2% – that is, all individual “instruction” about how we are organized, is the file size of 60 MB! This demonstrates the tremendous efficiency of the record information, which came up with the living systems in evolution. We have not yet approached such efficiency. Perhaps why not as long as I can “collect” such a complex system as man.
And what are the problems with the creation of the national Register?
– In Russia already there were attempts of creation of such Registers, but they all stayed on the number in the tens of thousands of samples in the database, then “did not grow”. The total number of potential donors in all these registers – about 70 thousand, and this is very small for normal operation of the system. It seems appropriate to integrate all existing registers in the unified Federal register, adding it to the number at least 500 thousand, and the best – a million potential bone marrow donors. With this number begins the fast, efficient work to find matching donors.
Recently, active development of this direction have joined the “Rusfond”. Thanks to the advent of new-generation sequencing that enables to reduce the cost and speed up the procedure of genotyping, a set of genotypes was greatly accelerated. If before the genotyping of one sample cost about 20 thousand rubles, today is about 7 thousand rubles. The high cost of such studies is, in particular, in the reagents. “Rusfond” cooperating with a Russian biotech companies –”DNA-Technology” in the direction of the creation of our Russian reagentic, allowing to carry out such a study for less money – about 4 thousand roubles.
At current prices the register size in million potential donors would cost 5-7 billion rubles. For many hundreds and even thousands of lives saved per year. Compare: the construction of the stadium “arena” in St. Petersburg cost about 50 billion rubles and that the country appeared full, functional registry with a good probability to find a donor for everyone in need of patients need only a tenth of these costs!
Now if this system will work if the “Rusfond” will begin to fill the base with new genotypes, probably this will connect and state. Moreover, now creating such a registry was very possible, in particular, and on price indices. Overall, the entire process of creating a full Registry (from one million samples) may take 2-3 years, if you buy the sequencers and debug an effective system of recruiting donors.
That is, the second problem – the donors?
Yes, volunteers who agree to enter the Register is not less of a problem than the price of genotyping. People are afraid to become bone marrow donors. Rnsmu. N. And. Pirogov, in particular, our donor movement cooperates in this respect with the “Rusfond”. It turned out that among medical students, a high percentage of those who agree to enter the Register: almost every donor donated blood for HLA–typing. “Rusfond” together with the National register of bone marrow donors name Vasi has Periodicalupdater typing during our fall Week of the donor. And was very pleased with the result, because the week to replenish the Register for nearly a thousand samples is a very good result.
Collected typing samples will be frozen and wait for the moment when in the laboratory, they will be able to perform. The laboratory can process several hundred samples a week. But most importantly, these samples are received, and in any case they will be included in the Register.
Donor import substitution
Tigran gagikovich, what is the participation of the University in the establishment of a National register?
– Medical students – this is the most healthy and important category of donors. Donor movement in our University there is a long time, and this year we have started to collect biological material for HLA typing. In one week we have 886 signed the agreement and handed over the blood sample for inclusion in the Register. This is a very good indicators. Naturally, there was a lot of work: we talked to potential donors about what are the contraindications for donation, as it happens. To one side is not to scare, but on the other hand, that the donor understand that he will once find the right patient who needs a transplant of his stem cells.
Two months before the event, we began to discuss it in social networks. We have students that underwent bone marrow transplantation, but we didn’t know about it. They in return told me how it was. One student in early childhood found a match in the Israeli register. And when the students learn that among them there are people who are saved by bone marrow transplantation, begin to better understand the importance of the idea. We have a student who had become a donor of stem cells. Found it at the Russian Register. And she told the students. I say students, but it is much broader than this, and interns, and graduate students, and staff (tipping is people under the age of 45).
If such a process will be established in other universities, not just medical, with the help of young people, I think we’ll make a great Register, where they will be efficient donors. We are ready to share the experience, ready to go to universities with our technology, tell us how we could combine these two actions at a high enough level.