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Medicine Science

Drug-Free Organ Transplants From Unrelated Donors 83

Posted by Soulskill
from the just-say-no dept.
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 elrous0 (869638) * on Thursday March 08, 2012 @05:29PM (#39294531)

    My cousin/sister needed a transplant and it was a bear finding a donor. And even then she had to take all kinds of anti-rejection drugs with really nasty side effects.

    • by Anonymous Coward

      My cousin/sister needed a transplant and it was a bear finding a donor.

      Your sister is also your cousin?

      • by kimvette (919543) on Thursday March 08, 2012 @05:40PM (#39294705) Homepage Journal

        It's his half sister, birthed by his aunt. Interestingly, his cousin is also his wife. They like to keep it in the family, you see.

        • by Hadlock (143607) on Thursday March 08, 2012 @07:15PM (#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.

          • by Anonymous Coward

            As a liver transplant recipient, I would never discourage ANYONE from volunteering to be a donor. But I would caution you about being a voluntary live donor of anything. In our support group here, one of the live kidney donors talked about the insurance companies that now deny him coverage because of his "preexisting condition".

            Utter bullshit if you ask me, but that's our healthcare system for you.

        • by Kyont (145761)

          Naw, that's just an old colloquial Kentucky term for "wife".

    • by betso.net (950024)
      Even if the results would have been published a year ago, exposure to options like this are preserved only to people participating in studies until the therapy is approved and established. This takes some 3-5 years at least. Also keep in mind that newer things are by far not always better. Btw., here is another interesting article regarding this topic showing that there is a lot of space to work in this direction: http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2012.03992.x/abstract [wiley.com]
      • My brother got a hematopoietic stem cells (HSCs) transplant a couple days ago. They wiped out his then existing immune system with chemo rather than radiation and chemo as in the article; them implanted the stem cells. Right now his WBC is zero where normal is 4,500-10,0000. Anyways getting a bone marrow transplant is a pretty harrowing experience in itself. While the new immune system may not be rejecting the transplanted kidney, there is also the whole rest of the body that may be rejected by the new immu

    • by sjames (1099)

      I had no idea they had bears doing that now. And we thought H1Bs were a problem.

    • by dalias (1978986)
      Yes the incest jokes are mildly amusing, but for those of you unaware, "cousin sister" is Indian English for "female cousin".
  • I wasn't aware that after a transplant the recipient was put on a lifelong immunosupression treatment. I thought either the organ is rejected or it is accepted and that's it.

    • by Nittle (1356899) on Thursday March 08, 2012 @05:54PM (#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.
    • by HAKdragon (193605)

      As somebody who had a kidney transplant, I really wish that was the case. I also wish that the immunosuppressants were less expensive (even with insurance).

      • by swilde23 (874551)
        I'm a liver transplant (2.5 years now) and I can second all of this. Though my doctors finally allowing me to take generic Prograf has made a huge dent in my monthly drug costs. Also, I'm extremely grateful that I don't have to take Prednisone (as many of the kidney transplant patients do for the the rest of their lives).
    • I had a kidney transplant close to 6 years ago. I have 3 immunosuppresive meds, 2 of which are fairly targeted, one is good old prednisone. And then 3 more to counteract the effects of these meds.

      I missed a pre-treatment (too complicated to get into) by about a year that would have let me (without much worry) leave off at least one medication, as I see it, for my situation. This pre-treatment has been available in Europe for quite some time (I'm USA). I have the benefit of being a life sciences resea
      • According to my Son's transplant surgeon, there are better outcomes on the standard protocol of steroids throughout life than the pre-treatment protocol.

    • by 91degrees (207121)
      This is one of the reasons why face and hand transplants are a little controversial. The drugs have side effects - mainly the hugely weakened immune system - so when it's about quality of life rather than the difference between life and death it's a lot harder to argue for the operation.
    • I wasn't aware that after a transplant the recipient was put on a lifelong immunosupression treatment. I thought either the organ is rejected or it is accepted and that's it.

      Common mis-conception, exacerbated by transplant seekers who are desperately seeking to avoid their own death and gloss over how much their post-transplant life is going to suck when pleading for donors.

  • by geekoid (135745) <dadinportland AT yahoo DOT com> on Thursday March 08, 2012 @05:34PM (#39294613) Homepage Journal

    cause I don't want to die.... ever.

    • by barc0001 (173002) on Thursday March 08, 2012 @05:43PM (#39294755)

      Hopefully future breakthroughs will be able to use organs from other sources or even artificial organs instead of relying on human donors. After all, we don't want to get into a situation like that Larry Niven short story where the demand for organs to extend peoples lives got so strong they started using convicted criminals as spare parts. And then to satisfy further demand, redefined what constituted a capital crime. Like jaywalking and littering...

      • by mdenham (747985)

        That's actually a pretty good description of the state of the world in his Known Space stuff prior to the Man-Kzin wars. (Though it doesn't help that the world's population is, if memory serves, somewhere around 18 billion at that point as well. It's looking like that particular guess for the population in the 2200s was high by a factor of 2 or more.)

      • by Anonymous Coward on Thursday March 08, 2012 @06:00PM (#39294985)
        Yeah, what a nightmare. Imaging if the prison industry got so big that the government started putting all sorts of people in prison for non-violet crimes. Eventually so much money would be involved that politicians would start trying to outdo each other at being tough on crime and start a never ending cycle of increasing penalties. They might even take away a judge's power to decide what penalty someone faces by creating mandating sentences. Imagine if say 1% of the US population was in prison. 1 out of 100 adults! Science fiction is scary.
    • cause I don't want to die.... ever.

      Wait until you've lived with sensory deprivation (failing eyesight, hearing, taste, smell, numbness in the extremities), relative dementia (declining ability to learn, remember, reason), reduced mobility, loss of fine motor skills, and chronic pain for a few decades. Also factor in that most of your old friends are suffering similarly, or dead, and if your children are typical, they've left you in the dust long ago.

      It comes on slowly, starting around age 20-30, and generally picks up steam around 50-70, ge

  • by Eponymous Hero (2090636) on Thursday March 08, 2012 @05:39PM (#39294687)
    in other news, the sale of claw-foot bathtubs and bagged ice has seen a dramatic increase
  • It remains unclear whether the secret to Ildstad’s recipe is the facilitating cells or the timing of a certain chemotherapy drug, called cyclophosphamide, that is used to prevent graft rejection and GvHD. “The facilitating cell adds an extra level of complexity that might not be necessary,” Tisdale says. The question is difficult to answer — all of the study subjects received the facilitating cells.

    Moreover, much about the cells themselves and the method used to isolate them remain shrouded in a veil of secrecy — Ildstad is seeking a way to commercialize the approach through a company she founded called Regenerex, based in Louisville. “It’s difficult to assess something that doesn’t provide the key methodology,” says Megan Sykes, director of the Columbia Center for Translational Immunology at Columbia University in New York. “Nobody is quite sure what these cells are.”

    So the good news is that this will likely be funded right through the trials phase. The bad news is that it'll come out the other end wrapped in IP restrictions and not widely available to the public as a standard procedure.

    • Re: (Score:3, Informative)

      by Anonymous Coward
      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 hemat
      • by Guppy (12314)

        since most of the subjects have been children with Sickle Cell and other types of anemia).

        Huh. Now that makes a lot of sense as far as recruiting goes. I was wondering how they found people willing to undergo the risk of an partial-match bone-marrow transplant (and how to justify it to an ERB) in addition to their solid organ transplant.

    • So the good news is that this will likely be funded right through the trials phase. The bad news is that it'll come out the other end wrapped in IP restrictions and not widely available to the public as a standard procedure.

      If there wasn't the potential for obscene profits, nobody would have put up the obscene funding required to do the research.

  • summary is wrong. (Score:4, Informative)

    by Medievalist (16032) on Thursday March 08, 2012 @06:25PM (#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 Dyinobal (1427207)
      Yep even if the headline is miss leading this is a big deal. Assuming these people remain rejection free.
    • by sjames (1099) on Thursday March 08, 2012 @06:35PM (#39295383) Homepage

      By drug free, they are referring to not requiring life-long treatment with immune suppressants. That's a REALLY big deal.

      • By drug free, they are referring to not requiring life-long treatment with immune suppressants. That's a REALLY big deal.

        And a really bad deal for Big Pharma profits, so I'm not expecting this to become ubiqutious anytime soon. No drug dealer likes losing their lifetime customers.

      • You got "insightful" for agreeing with me, and I didn't even get "informative" for quoting the relevant part of the summary. /. moderation gets more idiosyncratic every day!

  • by Binestar (28861) on Thursday March 08, 2012 @06:29PM (#39295327) Homepage

    My Daughter had a bone marrow transplant at the age of 18 months old and has been off immunosuppressants since 30 months of age. (She is currently 7 years of age with no rejection issues and no medications at all -- 100% cured, mild chimerism)

    I guess I thought that was common? Her donor was unrelated, but had a 10/10 match on HLA. That might be the magic. This study lists it working for a HLA mismatched recipient.

    Of course, I only have the knowledge you get when your daughter is going through the transplant process, not all the unrelated stuff that doesn't pertain to her actual condition.

    • by macaran (766186)
      I'm not sure this is actually true, but I believe bone marrow regenerates. So she probably doesn't have any of the donors bone marrow in her anymore. The suppression drugs are more for people who have actual organs transplanted, which will always have cells that are not from your body inside you.
      • by Binestar (28861)
        Oh, she still has the bone marrow in her. That is the point of the transplant. She had a condition called "Kostman's Syndrome" which to put short, meant her bone marrow had a genetic defect that she was unable to produce the white blood cells that fight bacteria. Not only is her bone marrow someone else's, if she were to take a DNA test on her blood she would show up as male, as the donor was a male. WIthout the donor's marrow, hers would go back to not producing neutrophils.
        • by macaran (766186)
          That's pretty awesome binestar! I'm glad modern medicine worked out for your family!
        • by TheLink (130905)
          The thing I'm wondering about this new treatment is why wouldn't immune cells from the donated marrow start attacking the host?
          • by epp_b (944299)
            From the abstract:

            We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells

            IMNAD, but I don't think blood stem cells for transplant are normally engineered before infusion, so that's what's new about this particular procedure.

    • by Guppy (12314)

      I guess I thought that was common? Her donor was unrelated, but had a 10/10 match on HLA. That might be the magic. This study lists it working for a HLA mismatched recipient.

      None of the 8 trial participants was a perfect match, ranging from 5/6 down to 1/6 (the article I have access to only lists the */6 system) with 4 organs coming from unrelated donors (the failed transplant case was actually a 3/6 related donor). Also, your daughter's very young age at transplant was a plus.

    • Marrow is a little different. It is less about avoiding rejection of the marrow and more about preventing the new immune system from attacking the patient's other tissues and organs (induced auto-immune disease). If she was take off, then that means the marrow was not producing GvHD.

      • by Riskable (19437)

        I'm not sure what the age cutoff is but pre-toddlers haven't developed their immune systems to the point where they would reject organs. There are limitations of course but having an ignorant immune system has its advantages.

        • by Binestar (28861)
          Interestingly enough, after her transplant she needed to have her titers checked to see where she was on her vaccination schedule. There were a few vaccinations she needed to get that she had already had, but due to the transplant she was now immune to Chicken Pox, having never received the vaccine nor had Chicken Pox, it was determined she inherited the immunity through the donor.
  • (I think the term comes from the word "bootleggers").

    Anyway, I wonder if young healthy people will start disappearing off the street. Maybe people will try to GET incurable chronic diseases (like HIV or Hepatitis) and have the fact that they are so infected indicated by a prominent tattoo (to ward off the organleggers. (The scarlet "H"?) Then of course, people will get the tattoos even if they don't have the disease I guess). Finally, maybe the death penalty will be enacted for even the most trivial of c

    • by dalias (1978986)
      This all sounds pretty far-fetched, considering that we're probably at most a decade or two away from making organ transplants completely obsolete (replaced by growing the patient's own replacement organ with their own DNA or slightly modified to correct for the genetic disease that caused the original organ to fail).
    • Anyway, I wonder if young healthy people will start disappearing off the street.

      I've heard stories from decades ago that imply that this has been happening in places like India for a long time. Fortunately there are only a handful of Indians wealthy enough to do this, and with a potential donor pool of over 1B, you've got far better odds of winning a $10M lottery with a single $1 ticket.

  • Funny.. I was just re-watching SGU and while encountering The season 2 episode "Hope", one of the secondary characters goes into end-stage renal failure. As part of his treatment, the medic on board describes how they found a kidney transplant procedure in which The Ancients used a bone marrow transplant beforehand to help prevent the donated organ from being rejected.

    Without having read the article, I'm going to guess that this was considered possibly feasible long before and the SGU writers picked up on

  • I had a stem cell transplant, SCT, (commonly referred to as a bone marrow transplant) 10 years ago to treat a bone marrow failure disease called Myelodysplasia (MDS). My older brother was the donor with a 5 out of 6 HLA match. About 3 months post transplant I started to experience GVHD (affecting liver, skin, eyes, lungs) which was controlled using a combination of immunosuppressants, cyclosporine and prednisone (a steroid). GVHD tends to have a more pronounced effect on the large, high surface area orga
  • As a 43-year-old male who has had a matched unrelated donor transplant (MUD) for acute mylogenous leukemia (AML, subtype M6) at age 35, I can tell you that having total body irradiation (TBI) and ablative chemotherapy is no walk in the park, and my chances of acquiring seconary cancers later in life is dramatically increased. So, for those requiring solid organ transplant, this approach is perhaps a win relative to the toxicity and other effects of lifelong immuneosuppression, I suspect it is far from a pa
  • Clinical Perspective (Score:4, Informative)

    by UltraOne (79272) on Friday March 09, 2012 @02:21PM (#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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