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Medicine Science

Drug-Free Organ Transplants From Unrelated Donors 83

ananyo writes "Researchers have for the first time managed to give patients a complete bone marrow transplant from an unrelated donor. The recipients were also able to accept kidneys from the same donors without the need for immunosuppressive drugs. Normally, such transplants would trigger graft-versus-host disease (GvHD) — an often deadly complication that occurs when immune cells from an unrelated donor attack the transplant recipient's tissue. The researchers report that five of eight people who underwent the treatment were able to stop all immunosuppressive therapy within a year after their kidney and stem-cell transplants, four of which came from unrelated donors (abstract)."
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Drug-Free Organ Transplants From Unrelated Donors

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  • by Nittle ( 1356899 ) on Thursday March 08, 2012 @06:54PM (#39294905)
    My father-in-law lived more than 20 years after a liver transplant and required medication to prevent rejection. I believe the initial anti-rejection drug changed a few years after the implant, but he still was required to take daily medication.
  • summary is wrong. (Score:4, Informative)

    by Medievalist ( 16032 ) on Thursday March 08, 2012 @07:25PM (#39295281)

    Eight recipients of human leukocyte antigen (HLA) mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil.

    That's directly from the abstract linked above. How 'bout that "drug free" headline there, eh?

    The real news is that a couple of these people were successfully weaned off immunosupressants. And only one of the patients died from the treatment I think (corrections appreciated).

  • by Hadlock ( 143607 ) on Thursday March 08, 2012 @08:15PM (#39295729) Homepage Journal

    I'm going to hang this off of your post because it's near the top of the thread:
      It's fast, easy and FREE to register as a marrow donor. They ask for an optional $100 donation to cover the cost of the test, but it's not required. The registry test involves swabbing the inside of your mouth, at home. It takes about 40 seconds (4 swabs @ 10 seconds each). It's completely painless and there are no needles or doctors involved.
      Join the Marrow Registry - [marrow.org]http://marrow.org/Join/Join_the_Registry.aspx [marrow.org]

    Obviously, registering to become a donor is an important and serious decision to make, but they're short on donors of people not of white/European descent. There's a high likelihood chance you'll never be asked to donate, but there's a 1 in 300,000 chance that you could save a life.

  • Re:The Fine Print... (Score:3, Informative)

    by Anonymous Coward on Thursday March 08, 2012 @11:05PM (#39296991)
    If you're curious, facilitator cells are CD4+, CD8+, and make up only a small fraction of the total number of T-cells. (CD4+ are "helper", CD8+ are "killer", and having both on one cell was thought to be impossible.) The processing includes ferromagnetically extracting 85% of the harvested bone marrow cells (collected over four donations per donor, often a parent since 3/6 HLA matches are acceptable, which is a major improvement over traditional technique), retaining the facilitator, progenitor, and hematopoetic stem cells (CD34+), while removing the alpha-beta B & T cells (which contribute to graph vs host), then verifying everything is within acceptable limits by flow cytometry. The facilitator cells also have something done to them, but I'd imagine fewer than ten people in the world know exactly what.

    From there, the recipient takes some chemotherapy drugs to reduce (but not eliminate, an important difference!) their own bone marrow. The goal is mixed chimerism, where both the donor's and recipient's bone marrow work together without killing each other so you have two populations of blood cells. The first advantage is that, if the graph fails, the recipient still has their original immune system. The second is, as the summary states, they don't have to be on immunosupressants for the rest of their life (which is hoped to be long, since most of the subjects have been children with Sickle Cell and other types of anemia).

    The researchers are highly secretive about the processing. They know that this discovery is likely to make someone rich, and perhaps Nobel-worthy if it is as successful as they hope (so they absolutely want to be the first to do it, even if the lack of collaboration makes things slower). Bone marrow transplant currently is the only cure for a great many disease, but has ~50% five-year mortality, whereas this technique seems to be much safer. I personally find such secrecy in research to be highly distasteful, so I distanced myself from the project and outright left when non-disclosure agreements were mentioned. It is absolutely groundbreaking though.
  • by dalias ( 1978986 ) on Friday March 09, 2012 @04:17AM (#39298495)
    Yes the incest jokes are mildly amusing, but for those of you unaware, "cousin sister" is Indian English for "female cousin".
  • Clinical Perspective (Score:4, Informative)

    by UltraOne ( 79272 ) on Friday March 09, 2012 @03:21PM (#39303999) Homepage

    I am a pediatric blood & marrow transplant physician. I have read the article abstract, but I don't subscribe to Science Translational Medicine, so I won't be able to read the article until my hospital library orders & acquires the article. These comments are based only on the abstract.

    The Slashdot summary is misleading about what is novel in research. Unrelated donor bone marrow transplants (or hematopoietic stem cell transplants (HSCT), which are a superset) have been done routinely since the 1990's.

    Allogeneic (meaning the stem cell source is another person, rather than the patient himself/herself) HSCT patients take immunosupressive medications to try to prevent (or to treat) graft versus host disease (GVHD). If the patient does not develop GVHD, they are usually weaned off the immunosuppressive medications by 6 months after transplant. Patients who do develop GVHD can require years (sometimes 5-10 years) of immunosuppression. In contrast, patients who receive common solid organ transplants (heart, liver, kidney) are usually on immunosuppressive medications for life, although the immunosuppression is typically stronger for the first few months after transplant. The article reports on patients who received simultaneous kidney and HSC transplants from the same donor. Some of these patients could be weaned off of immunosuppression. Although this type of simultaneous transplant is not common, it has been reported before, as well as the finding that patients could come off immunosuppression.

    What is novel is the ability to perform unrelated donor transplants using donors who were not good HLA matches (the matching system that is used for HSCT) and not have the recipients develop GVHD. This was accomplished by manipulating the stem cell product after it had been collected from the donor, but before it was infused into the recipient. The majority of HSCT done today are done with unmanipulated stem cell products (I'm not counting processing that often needs to be done when the donor and recipient don't have the same red cell type - which is controlled by a different genetic system than HLA). However, some forms of stem cell product manipulation (T-cell negative selection and CD34+ cell positive selection) have been around for a few decades. They can be successfully used to decrease the risk of GVHD, but at the price of increasing the risk of graft rejection, relapse (for leukemias) and infection. In the end, almost all studies of those methods show that the overall survival or disease-free survival is unchanged.

    This article describes a more sophisticated form of stem cell manipulation, in which the graft is enriched in hematopoietic stem cells and tolerogenic graft facilitating cells. There have been past reports of other sophisticated stem cell manipulations giving good results in a study, but these techniques require elaborate facilities to perform, and often when they have been replicated by groups other than the original group, the patient outcomes have not been as good as those in the original report.

    So my bottom line is that this result is exciting, but needs at minimum validation in a multicenter study before it starts to look like a game changer.

    To address some of the other comments:

    1) The concern about graft-versus-leukemia effects is a valid one and it will need to be studied. However, that is not an issue when doing a transplant for a non-malignant disease, so it would be a definite win for those patients. For leukemias, the GVL effect is strongest in CML, then AML, and weakest in ALL (kids don't get CLL, so I don't know much about that disease). Ultimately it would take clinical trials to determine if the benefit from less GVHD outweighs increased relapse risk (if any) from decreased GVL.

    2) The article uses reduced-intensity radiation / chemotherapy, which isn't exactly a picnic, but it is less toxic than standard-dose (10-14 Gy) total body irradiation and 120 mg/kg cyclophosphamide (or 4 day busulfan and 120-200 mg/kg cyclophosphamide).

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