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Thread: Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

  1. #1

    Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

    BACKGROUND:
    Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.

    CASE PRESENTATION:
    We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation.

    CONCLUSION:
    Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s).

    http://www.ncbi.nlm.nih.gov/pmc/arti...3/?tool=pubmed

  2. #2
    Moderator jody's Avatar
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    so you might get healed of sci, but the immune response causes crippleing rheumatic bone inflamation and bone changes. that is a little disheartening to think about, but not surprising.

  3. #3
    While I appreciate the concern, I was taken aback by the claims in this paper. Let me explain why.

    The authors report a single case of spondyloarthropathy in a patient, who also happened to have gotten "allogeneic stem cell therapy". Based on this, the authors conclude "Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons."

    Millions of people have received "allogenic stem cell therapy" in the form of blood transfusions. Peripheral blood contains stem cells and they are usually allogeneic. I am not aware of an epidemic of undifferentiated spondyloarthropathy in patients who have received blood transfusions.

    Hundreds of thousands of people who now received "allogenic stem cell therapy" in the form of umbilical cord blood and bone marrow transplants.
    Again, I am not aware of an epidemic of spondyloarthropathy in these patients who have received this clearly allogeneic stem cell therapy.

    So, here is a single case and the authors claim that it supports their hypothesis that "de novo rheumatic disease can develop after stem cell transplant for a variety of reasons". I therefore went to look at this paper more carefully. I attach a copy of it for people's perusal.

    The paper itself is a bit more reasonable than its abstract. It cites several older papers that reported the development of arthritis in patients who have receive bone marrow transplants, i.e. as listed below.

    4. Wagener P, Schulte D, Link H, Kirchner H, Stoll M, Poliwoda H:
    Musculoskeletal manifestations in patients after bone marrow transplantation. Initial clinical rheumatologic observations. Z Rheumatol 1991, 50:199-203.
    5. Barnabe CCM, LeClercq SA, Fitzgerald AA: The development of inflammatory arthritis and other rheumatic diseases following stem cell transplantation. SemArthritisRheum2008,39:55-60.
    6. Daikeler T, Tyndall A: Autoimmunity following hematopoietic stem-cell transplantation. Best Pract Res Clin Haematol 2007,20:349-360.
    7. Imamura R, Inoue H, Kato K, Kobayashi S, Tsukamoto H, Nagafuji K, Shimoda K, Nakashima H, Otsuka T, Gondo H, Harada M: Development of rheumatoid arthritis following autologous peripheral blood stem cell transplantation. Bone Marrow Transpl 2002,30:527-529.
    8. Koch B, Kranzhofer N, Pfreundschu M, Pees HW, Trumper L: First manifestations of seronegative spondyloarthropathy following autologous stem cell transplantation in HLA-B27-positive patients. Bone Marrow Transplant 2000, 26:673-675.
    9. Daikeler T, Gunaydin I, Kotter I: Transmission of psoriatic arthritis by allogeneic bone marrow transplantation for chronic myelogenous leukemia from an HLA-identical donor. Rheumatology (Oxford) 1999, 38:89-90.
    Yes, indeed, bone marrow transplants may cause arthritis for several reasons that make it very different from other kinds of stem cell transplants. First, bone marrow transplants replace the bone marrow, which of course makes immune cells. Therefore, one would expect bone marrow cells that carry genes for rheumatic arthritis or other conditions, to cause such diseases in the recipients. Second, bone marrow transplants have a very high incidence (>70%) of graft-versus-host-disease (GVHD). This is when the donor cells attack the recipient's body because they are "foreign". Manifestations of GVHD can include musculoskeletal arthritis. Third, many of the patients who have received bone marrow transplants usually have very serious diseases and treatments, including leukemia and chemotherapy and the complications of such diseases and treatment, that can predispose to all types of musculoskeletal ailments, including arthritis. This particular patient happened to have been treated with bone marrow transplants for pre-B lymphocytic leukemia and was in remission.

    Upon further study of this case history, it is not clear that the authors have any evidence whatsoever that supports their hypothesis that this man's spondyloarthritis resulted from his allogeneic stem cell transplant.

    This patient has had a lot of therapy for his leukemia, which the authors claimed was refractory to chemotherapy. The patient received a haploidentical allogeneic bone stem cell transplants (presumably bone marrow) from his father. The donor of the bone marrow, the patient's father, apparently had no psoriasis or arthritis history.

    By the way, to do that, they are likely to have given him myeloablative chemotherapy including radiation therapy, both of which should predispose him to spondyloarthritis. By the way, it is inexcusable that they did not say whether he had any GVHD.

    I find it bizarre that the authors claim that this is an autoimmune disease and then did nothing to test for this possibility. So, what is this person's rheumatic arthritis factors? Did his father's bone marrow engraft? Did his blood type switch to his father's etc.

    In my opinion, this not a good study and really doesn't provide any convincing data that allogeneic stem cell transplants cause arthritis.


    Quote Originally Posted by dr.zapp View Post
    BACKGROUND:
    Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.

    CASE PRESENTATION:
    We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation.

    CONCLUSION:
    Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s).

    http://www.ncbi.nlm.nih.gov/pmc/arti...3/?tool=pubmed

  4. #4
    Thanks for the commentary, Wise! I was a little suspicious about this paper too, and posted it hoping you would comment, since this is not my area of specialty.

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