Bone marrow transplantation for HIV patients. Two patients became HIV-free after bone marrow transplantation. How is a bone marrow transplant done?

One of the reports about the successful cure of a patient from HIV came from doctors from the USA, who spoke about their results at the International AIDS Society Conference to Kuala Lumpur. Timothy Henrich and Daniel Kuritzkes from two Boston clinics spoke about two of their patients in whom no traces of HIV were found in the blood after bone marrow transplantation, despite the fact that one of them did not receive antiviral therapy for fifteen weeks after the operation, and the other - within seven. In both cases, transplantation was prescribed to patients due to developing Hodgkin lymphoma, a type of cancer of the lymphatic system.

If in the future the message of Boston doctors is confirmed, it will be a very serious success, because today it is extremely difficult to rid a person of the HIV infection that has settled in him.

The virus has a habit of hiding in a person's DNA so that it becomes completely elusive. Antiretroviral therapy (ART) used today helps rid the patient of viruses in the blood, but as soon as treatment is stopped, HIV viruses reappear and begin to multiply rapidly.

Both patients in question had been HIV positive for approximately 30 years. Both developed Hodgkin's lymphoma (or lymphogranulomatosis), and to such an extent that neither chemotherapy nor other treatments no longer helped and the only way to save them was a bone marrow transplant. Both operations were successful, and after them, viruses were not detected in the blood of one of the patients for four years, and for two years in the other. Even after their ART therapy was stopped.

This result indirectly confirms the opinion of many experts that the bone marrow, where blood cells are born, is the main refuge for AIDS viruses.

True, the doctors themselves emphasize that it is too early to talk about treating HIV infection in this way. “We have not proven that our patients are cured,” says Timothy Henrich. “This requires much longer observations. The only thing we can say with certainty is that as a result of transplantation, the virus does not return to the bloodstream for a year or two after we stop treatment, and that the chances of it returning are extremely low.”

“We showed,” he adds, “that the number of viruses in the blood of these patients decreased by 1,000-10,000 times. However, the virus may still be present in the brain or digestive tract."

In fact, the message from Boston doctors cannot be considered the first of its kind. It was preceded by an article in the magazine Blood, in 2010, about Timothy Brown, a patient at the Charite clinic at the Medical University of Berlin. The man suffered from acute myeloid leukemia, a cancer in which abnormal white blood cells develop abnormally quickly. He was also HIV-infected and also underwent a bone marrow transplant, after which no HIV viruses were detected in his blood. True, there was one peculiarity - the donor had one very rare gene mutation that protected him from AIDS viruses. Therefore, all the assurances of doctors that it was bone marrow transplantation that cured the patient from harmful viruses did not inspire complete trust.

But even if it is 100% proven that a bone marrow transplant can certainly rid a person of HIV infection, it is unlikely that this will become a standard method.

In all cases, the transplant was prescribed to treat cancer, not HIV infection. It is also prescribed for cancer as a last resort. This is not only very expensive, but also very dangerous - in 20% of cases, patients do not survive such an operation. In addition, before the operation it is necessary to weaken the patient's immune system as much as possible in order to avoid the risk of transplant rejection, which is also very risky. In the Boston report, by the way, there is a message about a third patient, also HIV-positive and also forced to undergo a bone marrow transplant: he died of cancer.

Bone marrow is a special human organ responsible for hematopoiesis, and more precisely, for the reproduction of red blood cells, immune cells and, to some extent, even neurons. Bone marrow is a kind of liquid substance located in the cavities of the large bones of the skeleton, consisting mainly of stroma - cells of unformed connective tissue and stem cells.

Stem cells are special cells of the body from which the human embryo is formed. During embryonic development, these cells divide very actively, and then acquire specialization, turning, for reasons only known to them, into certain tissues and organs.

In an adult, there are remnants of these cells located in the bone marrow, which have lost the ability to reproduce, but can still reproduce any tissue in the body, patching up the gaps formed due to the massive death of cells for various reasons. These cells contain the secret of eternal youth, and, possibly, eternal life, however, they are not fully understood.

Experiments on mass stem injections for the purpose of rejuvenation failed due to the massive incidence of cancer among people undergoing the procedure. But transplanting stem cells into sick people whose bodies have been damaged by anti-cancer therapy in order to restore immunity, blood or other tissues shows excellent results.

The stroma is a kind of foundation (and from Greek it is translated as litter) for stem cells; it is capable of phagocytosis - eating pathogenic or foreign cells.

The stroma consists of two types of cells:

  • Osteoblasts are cells that separate the bone marrow and blood and are the support of the bone marrow.
  • Resorblasts are giant cells with a huge number of nuclei, amounting to 12 pieces, which remove bone tissue, destroying mineral components.

Simply put, the former build bones, and the latter destroy them. This continuous process ensures constant renewal of the skeleton.

Also in the bone marrow there are special hematopoietic cells - a type of stem cells capable of reproducing blood cells according to the number of their sprouts, of which there are 5 in a mature state, each of which reproduces a certain type of blood cell.

Human bone marrow is divided into two types: red and yellow. Red is responsible for hematopoiesis, and yellow no longer produces anything and replaces red as a person grows older.

It is the red bone marrow that is of interest for transplantology and is located in the spongy substance of flat bones, the middle of tubular bones, and also contains the spinal cord, but this organ is inviolable.

Image caption The HIV virus hides in a certain type of tissue, creating inaccessible
tanks

American doctors managed to stop taking antiviral drugs in two patients with HIV through a bone marrow transplant.

One of the patients has been off antiretroviral drugs for four months and has no signs of the virus returning.

A group of doctors at Brigham and Women's Hospital in Boston published a report on their findings in the proceedings of the International HIV Society conference.

However, doctors warn that it is too early to talk about a complete cure, and that the virus could return at any minute.

Complete elimination of the causative agents of this terrible disease is difficult, since the virus hides inside human DNA molecules, creating “reservoirs” that are inaccessible to drugs.

Antiviral drugs stop the virus from spreading, but if they are stopped, the virus usually returns.

Disappearance of the virus?

The two patients, whose names have not been disclosed, became infected with the HIV virus about 30 years ago.

Both developed cancer - lymphoma, which required bone marrow transplants.

The bone marrow is the organ that produces new blood cells and is also considered the main reservoir for the HIV virus.

After a bone marrow transplant, the presence of the HIV virus was not detected in the blood of one of the patients for two years, and for another - for four years.

Both patients stopped taking antiviral drugs earlier this year.

For one of them, 15 weeks have passed since then, for the other - seven, but no signs of the virus returning have yet been found.

Dr. Timothy Heinrich said the results were encouraging for the researchers. However, he is cautious.

“We have demonstrated not a cure, but the absence of signs of the virus for a long period,” he said.

Doctors believe that the transplanted bone marrow was protected from infection by a course of antiviral drugs. Meanwhile, the new bone tissue destroyed the old tissue in which the virus took refuge.

However, Dr. Henrich believes that the virus may be hiding in brain tissue or in the digestive tract.

"If the virus does return, this would mean that these areas are reservoirs of the virus, and that methods of controlling the virus in these areas of the body will need to be reconsidered," the researcher said.

Berlin patient

Timothy Brown, known as the "Berlin Patient", is believed to be the first person to be completely cured of HIV infection. He underwent a bone marrow transplant from a donor who had rare resistance to the HIV virus.

Two patients in the United States received transplants from conventional donors.

ANALYSIS

It is too early to call this a cure for HIV. And even if this method turned out to be such a cure, it is not suitable for everyone.

It is extremely expensive and often leads to immune incompatibility. The risk of death during the first few years after transplantation is 15-20%.

This occurs when new immune cells produced by the transplanted bone marrow begin to attack the entire body, mistaking it for a foreign body.

For two patients in this study, their usual course of antiretroviral drugs was replaced with drugs that suppress the immune system.

Transplantation was only possible for these patients because they developed cancer of the lymphatic system.

The real value of this research lies in the deeper understanding of the nature of the HIV virus and its behavior in the body.

Previously, it was also reported that a baby born in Mississippi, USA, had been completely cured. The girl was given antiviral drugs immediately after birth and it is believed that the virus was eliminated in her blood before it could create reservoirs.

Dr Michael Brady, medical director of the Terence Higgins Foundation, said it was too early to know whether the HIV virus had been eradicated from these patients.

"However, this case suggests that what happened to Timothy Brown, the Berlin patient, was not an exceptional phenomenon. Bone marrow transplantation is a complex and expensive procedure that carries significant risks," he said.

For most people with HIV, such a transplant would be riskier than continuing to take antiviral drugs that block the spread of the virus, he said.

The head of the HIV Research Foundation, Kevin Frost, believes that the results obtained by American researchers provide important new data that could change our understanding of HIV and gene therapy.

"These new observations could lead researchers to new approaches to treatment, and even to the complete eradication of the HIV virus," the scientist said.

Amplatz Children's Hospital. Photo from archdaily.com

A 12-year-old American man who was trying to be cured of HIV and leukemia with a bone marrow transplant died as a result of graft-versus-host disease, Medical Daily reports. The death of Eric Blue occurred on July 5, but this became known only now.

On April 23, 2013, at Amplatz Children's Hospital at the University of Minnesota (Minneapolis), the boy underwent an operation similar to that which cured Timothy Brown of HIV and leukemia - the so-called “Berlin Patient”, currently considered the only documented case of complete recovery from HIV infection. American Brown, who lives in Berlin, underwent a stem cell transplant taken from a donor who had a genetic mutation that gave him natural immunity to HIV in 2007. After the transplant, Brown was in complete remission and was able to stop antiretroviral therapy and To this day he is completely free of signs of both diseases.

In addition, at the conference of the International AIDS Society, held from June 28 to July 3, 2013 in Kuala Lumpur (Malaysia), a group of researchers from Brigham and Women's Hospital (Boston, USA) spoke about the successful treatment of HIV and lymphoma using bone transplantation brains in two men who had previously lived with the virus in their blood for about three decades.At the same time, the authors of the report emphasized that there can be no talk of a complete cure yet.

Eric Blue received cord blood cells from a donor with natural immunity to HIV. The ultimate goal of the procedure was to completely replace Eric's immune system cells with donor ones. To achieve this, the boy's own immune system was suppressed using chemotherapy.

At first everything went well, laboratory tests showed that Eric's blood was free of both HIV and leukemia, even when he stopped taking his medications. However, in June, the boy developed graft-versus-host disease, when the donor's immune cells attack the recipient's body. This reaction develops in 60-80 percent of cases of unrelated donation.

“In Eric’s case, we knew it was a big risk and success was not at all guaranteed,” said transplant specialist Michael Vernaris. “Nevertheless, we will continue, based on the experience gained, to try to introduce a new method of HIV therapy.”

Comments (10)

    20.07.2013 13:54

    Kostya

    We need to put this technology on stream and cure all HIV-infected people, and let the pharmaceutical suckers with their ineffective drugs suck

    20.07.2013 15:49

    Welder

    Quote 1, title:
    “A bone marrow transplant did not save a boy with HIV and leukemia”
    Quote 2, text:
    "Eric Blue received umbilical cord blood cells"

    On the medical portal, do you differentiate between “Bone Marrow” and “Umbilical Cord Blood” donor materials?

    20.07.2013 23:48

    Lemmy666

    “In other words: they used the boy as a laboratory mouse.”
    What is better - a 20-40% success rate or zero?

    21.07.2013 19:08

    Laura

    To the welder. Bone marrow is transplanted, roughly speaking, it is simply a blood transfusion. And umbilical cord blood contains many stem cells that populate the patient’s empty bone marrow and begin to mature and multiply there. This is sketchy.

    21.07.2013 20:52

    A vampire

    Bone marrow is a spongy substance of bone tissue, umbilical cord (placental) blood is blood obtained during natural childbirth in the delivery room or after a cesarean section in the operating room.
    Hematopoietic stem cells are isolated from both bone marrow and umbilical cord blood, which are subsequently used for transplantation; however, cord blood generally contains fewer stem cells than bone marrow.

    22.07.2013 00:47

    Lemmy666

    Vladimir Ramenskii, what's the point? After all, the task was to transplant cells from a person with immunity from HIV, but the relatives probably did not have it

    22.07.2013 07:47

    Welder

    For Vladimir Ramenskii

    As for the experimental mouse: the boy had nothing to lose. The operation that was performed on Timothy Brown and this boy is used only as a last resort when chemotherapy and ART do not provide the desired effect. Please note that both patients were treated for TWO fatal diseases at once. The first one worked well; he had good compatibility; from a small bank of donors with the CCR5 delta12 mutation, they were able to find several compatible samples for him and select the most suitable one.

    29.07.2013 21:34

    Violet

    My neighbors have a little daughter, she’s only 2 years old. So small and active all the time, as long as I remember. And then one day her mother comes and asks for help with money for treatment. The baby was diagnosed with leukemia, chemotherapy was given, but she needed a bone marrow transplant, and this operation was expensive. They found a clinic in Turkey, where they promised to help them, and the prices there were lower than European ones. Upon their arrival, we went to visit the baby, they said that the operation went well and now the child is gradually recovering, and she no longer looked so yellow. Alina said that the doctors at the Memorial clinic are very courteous and take care of each patient. They didn’t take an extra penny, the amount they initially agreed on was what they paid. Now the main thing is that this whole nightmare leaves their lives and never returns.