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U of M begins nation's first clinical trial using T-reg cells from cord blood in leukemia treatment
By Dross at 2007-09-06 21:00

University of Minnesota researchers have initiated a ground breaking clinical trial to determine the optimal dose and safety of T regulatory cells (T-regs) to decrease the risk of immune reactions common in patients undergoing blood and marrow transplantation.

Ultimately, the researchers hope the experimental cellular therapy will improve overall survival rates for blood cancer patients as well as offer a potential new paradigm for treating autoimmune diseases.

“Toward our quest of making transplants even safer for adults and children with leukemiaterm, lymphomaterm, multiple myeloma, and other blood and marrow disorders, we are exploring the possibility of using T-regs to enhance the rate of blood and marrow recovery and reduce the risks of graft-versus-host disease, a complication that affects more than 60 percent of patients,” said Claudio Brunstein, M.D., principal investigator of the study.

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CD25 expression on donor CD4+ or CD8+ T cells is associated with an increased risk for graft-versus-host disease
By Dross at 2007-04-02 23:59

Graft-versus-host disease (GVHD) occurs in an unpredictable fashion after 30% to 50% of matched-related transplantations. The presence of increased frequencies of CD4( )CD25( ) regulatory T cells in donor grafts has been shown to ameliorate GVHD after allogeneic transplantation in murine models. To determine whether a similar relationship exists in humans, we quantitated the coexpression of CD25 on CD4( ) and CD8( ) T cells within 60 donor grafts infused into matched siblings and examined GVHD incidence in the respective recipients. Recipients in whom GVHD developed received donor grafts containing significantly higher frequencies of CD4( ) T cells coexpressing CD25 than those who did not (median, 9.26% vs 2.22%; P =.004). Frequencies of donor graft CD8( ) T cells coexpressing CD25 were also higher (0.65% vs 0.14%; P =.002). Furthermore, transplant recipients who received grafts containing fewer CD4( )CD25( ) and CD8( )CD25( ) T cells were less likely to acquire acute GVHD, even though these donor-recipient pairs were similar to others with respect to relevant clinical variables. These data suggest that the coexpression of CD4 and CD25 may be insufficient to identify regulatory T cells in humans and that increased frequencies and numbers of CD25( ) T cells in donor grafts is associated with GVHD in transplant recipients.

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Functional assessment and specific depletion of alloreactive human T cells using flow cytometry.
By Dross at 2007-04-02 23:57

Human T-cell alloreactivity plays an important role in many disease processes, including the rejection of solid organ grafts and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. To develop a better understanding of the T cells involved in alloreactivity in humans, we developed a cytokine flow cytometry (CFC) assay that enabled us to characterize the phenotypic and functional characteristic of T cells responding to allogeneic stimuli. Using this approach, we determined that most T-cell alloreactivity resided within the CD4( ) T-cell subset, as assessed by activation marker expression and the production of effector cytokines (eg, tumor necrosis factor alpha [TNF]alpha) implicated in human GVHD. Following prolonged stimulation in vitro using either allogeneic stimulator cells or viral antigens, we found that coexpression of activation markers within the CD4( ) T-cell subset occurred exclusively within a subpopulation of T cells that significantly increased their surface expression of CD4. We then developed a simple sorting strategy that exploited these phenotypic characteristics to specifically deplete alloreactive T cells while retaining broad specificity for other stimuli, including viral antigens and third-party alloantigens. This approach also was applied to specifically enrich or deplete human virus-specific T cells.

read more | 2155 reads

H. Lee Moffitt Researchers Discover Potential Targets to Reduce Risk of Stem Cell Transplants
By Dross at 2007-02-21 00:58

Inhibiting one gene -- even temporarily -- can improve cure rates for blood cancer patients who receive stem cell transplants. This strategy may also help patients with genetic and autoimmune diseases who are also treated with stem cell transplants. Researchers at H. Lee Moffitt Comprehensive Cancer Center in Tampa, led by William Kerr Ph.D., and funded by The Leukemiaterm & Lymphomaterm Society, have discovered that the SHIP gene plays a critical role in graft vs. host disease (GvHD), in which a donor's immune cells (the "graft") attack a stem cell transplant patient's healthy tissue (the "host") as well as cancer cells. By using genetically engineered mice, the researchers have shown that inactivating the SHIP gene for just one week protects transplant recipients from acute GvHD. This protection is seen even when the graft contains extra immune cells to help the graft "take" or when the graft cells are completely mismatched to the recipient. The findings will be published in the March 1st issue of the "Journal of Immunology."

read more | 1931 reads

Study Indicates Increased Second Solid Cancers After Stem Cell Transplantation
By HCat at 2007-02-10 00:45

    A statistical review of case files from 926 patients in British Columbia, Canada was conducted by Genevieve Gallagher, MD and Donna Forrest, MD. The patients had received allogeneic hematopoietic stem cell transplantations (allo-HSCT) mainly from bone marrow (87%) and peripheral blood (12%).
Allogeneic means taken from different individuals but the same species.

    Patients had received allo-HSCT treatment for a variety of diagnosis, mainly (95%) including AML, ALL, CML, MS, lymphoproliferative disorder, and multiple myeloma. Risk factors that were analyzed in the study included Donor/recipient sex combination, graft-versus-host-disease (GvHD), and age. The analysis looked for patients who developed a second solid malignancy after transplantation, and then correlated risk factors that would indicate an increased chance of developing a second solid malignancy.

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New drug therapy to combat GVHD in stem-cell patients shows significant reduction in deaths
By Dross at 2007-01-24 07:26


Gastrointestinal graft-vs.-host disease is a common and potentially deadly side effect for patients who undergo an allogeneic stem-cell transplant to treat certain blood cancers. Now, new research from Fred Hutchinson Cancer Research Center shows that adding a widely used topical corticosteroid to the standard treatment for GVHD kept the disease in remission and significantly reduces deaths one year after therapy.


A reformulation of beclomethasone dipropionate (BDP) into two different pills specifically releasing the drug into the stomach and mid-small intestine prevented relapse of gastrointestinal GVHD and allowed those patients to be on a shorter treatment course of high-dose prednisone. Mortality was reduced by 46 percent a year following the start of treatment in a multi-center Phase III clinical trial, according to findings published today in the online edition of the journal Blood.

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Bone Marrow Transplantation - Abstract of article: Regulating regulatory T cells
By Dross at 2006-12-21 00:06

Understanding Regulatory T Cell operation in Bone Marrow Transplants is integral to understanding Graft vs Host disease and is important in helping you find a BMT center and trial that takes this into account. Begin in your understanding by reading this article.

[via Bone Marrow Transplantation - Abstract of article: Regulating regulatory T cells]:

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

read more | 2138 reads

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