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Bone Marrow Transplant
New Technology Enhances and Expands “Homing”and Therapeutic Potential of Cord Blood Stem Cells in Bone Marrow Transplants
By Dross at 2008-06-07 01:17

Rush University Medical Center researchers present pre-clinical data at international symposium June 6-7

A CD26 Inhibitor increases the efficiency and responsiveness of umbilical cord blood for bone marrow transplants and may improve care for blood cancer patients according to research from Rush University Medical Center being presented at the 6th Annual International Umbilical Cord Blood Transplantation Symposium, June 6-7 in Los Angeles.

Kent W. Christopherson II, PhD, assistant professor of medicine and researcher in the Sections of Hematology and Stem Cell Transplantation at Rush, is researching a CD26 Inhibitor, a small molecule enzyme inhibitor that enhances directional homing of stem cells to the bone marrow by increasing the responsiveness of donor stem cells to a natural homing signal. Homing is the process by which the donor stem cells find their way to the bone marrow. It is the first and essential step in stem cell transplantation.

Cord blood is increasingly being used by transplant centers as an alternative source of stem cells for the treatment of blood cancers, including myeloma, lymphomaterm and leukemiaterm. The cells, which are collected from the umbilical cord after the baby is delivered and separated from the cord, are most commonly used for bone marrow transplantation when a donor from a patient’s family or an unrelated donor does not produce an appropriate bone marrow match.

The current drawback to the usage of cord blood cells is that due to the limited volume and cell number, there are generally only enough cells available from a single cord blood collection for children or very small adults. Cord blood cells also usually take longer to engraft, leaving the patient at a high risk for infection longer than donor matched transplanted marrow or peripheral blood stem cells. The goal of Christopherson’s research is to increase the transplant efficiency of umbilical cord blood and ultimately make transplant safer and available to all patients who require this treatment.

In his discussion on “Strategies to Improve Homing,” Christopherson states that results from his and other laboratories suggest “the beneficial effects of the CD26 Inhibitor usage and the potential of this technology to change hematopoietic stem cell transplantation.”

Christopherson will co-chair the session and review some of his Leukemia & Lymphoma Society funded work at the symposium in a session entitled “Basic Science and Clinical Studies Addressing Obstacles to Successful Umbilical Cord Blood Transplants (UCBT)”.  He will be joined by Dr. Patrick Zweidler-McKay of the University if Texas MD Anderson Cancer Center. Zweidler-McKay will discuss his team’s work in the same session on Engraftin™, a human recombinant enzyme technology that increases the efficiency of engraftment and reduces graft failure in transplantation of cord blood derived stem cells.

Research results in animal models by Christopherson and Zweider-McKay show that both Engraftin and CD26 Inhibitor can enhance homing and rate of engraftment, which will result in reduced patient morbidity and mortality in bone marrow transplants. American Stem Cell, Inc., the developer of both technologies, plans to begin human trials in the next few months.

There are over 250,000 new cancer patients per year who require or would benefit from stem cell transplantation and as many as 20% are unable to find a blood or marrow match.

1108 reads

Lung Function Predicts Mortality After Stem Cell Transplant
By Dross at 2007-12-29 00:26

Pulmonary function tests are often performed before hematopoietic stem cell transplantation to screen for underlying respiratory problems. Recent research has suggested that pretransplant pulmonary function tests—particularly a measurement combining FEV1 and the diffusing capacity of carbon dioxide (DLCO)—can predict posttransplant respiratory failure and mortality.1

Jason Chien, MD, and colleagues retrospectively studied the pretransplant pulmonary function and arterial blood gasses of 2,852 cancer patients who received allogeneic stem cell transplants during a 12-year period. FEV1, FVC, total lung capacity, DLCO, and alveolar-arterial oxygen tension difference (PaO2) were measured. Patients in the nonmyeloablative group received 2Gy total body irradiation. Those in the myeloablative group received either total-body-irradiation-based or non-total-body-irradiation-based regimens. According to Dr. Chien, an Assistant Professor of Pulmonary and Critical Care Medicine at the Fred Hutchinson Cancer Center, “Assessment of pretransplant pulmonary function tests is very important, given their relationship with mortality risk. We would like to see every transplant center in the world screen their patients with pretransplant pulmonary function tests.”

read more | 3941 reads

For women, Pathenogenesis is now a reality
By Dross at 2007-12-22 22:10

New Rochelle, NY, December 19, 2007—In a groundbreaking experiment published in Cloning & Stem Cells, scientists from International Stem Cell (ISC) Corp. derived four unique embryonic stem cell lines that open the door for the creation of therapeutic cells that will not provoke an immune reaction in large segments of the population. The stem cell lines are “HLA-homozygous,” meaning that they have only the genetic profile of the mother, but duplicated. Every egg from a woman has one copy of the information needed to raise a woman. Humans need two copies, and the second is usually provided by the father, including either an X or a Y. A group of researchers has simply copied the half that already existed in the egg, and created a new cell with the potential to grow into bllod cells, nerve, or any other needed cell type. This is different to cloning, which would be an exact replica of the mother. The lines could serve to create a stem cell bank as a renewable source of transplantable cells for use in cell therapy to replace damaged tissues or to treat genetic and degenerative diseases. 

read more | 3950 reads

Cancer-resistant mouse could make BMT a fountain of youth
By Dross at 2007-11-28 21:09

LEXINGTON, Ky. (November 27, 2007) − A mouse resistant to cancer, even highly-aggressive types, has been created by researchers at the University of Kentucky. The breakthrough stems from a discovery by UK College of Medicine professor of radiation medicine Vivek Rangnekar and a team of researchers who found a tumor-suppressor gene called "Par-4" in the prostate.

The researchers discovered that the Par-4 gene kills cancer cells, but not normal cells. There are very few molecules that specifically fight against cancer cells, giving it a potentially therapeutic application.

read more | 1706 reads

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.

read more | 2430 reads

MGH researchers confirm that bone marrow restores fertility in female mice
By Dross at 2007-08-01 08:24

A new study from Massachusetts General Hospital (MGH) researchers confirms that female mice that receive bone marrow transplantation after fertility-destroying chemotherapyterm can go on to have successful pregnancies throughout their normal reproductive life. The report in the August 1 Journal of Clinical Oncology verifies that donor marrow can restore fertility in female mice through an as-yet unidentified mechanism. While donor-derived egg cells or oocytes were observed in the ovaries of marrow recipients, all pups born were from the recipients’ own eggs.

“Consistent with our past work, cells derived from the donor bone marrow are getting into the ovaries and developing into immature oocytes,” says Jonathan Tilly, PhD, director of the Vincent Center for Reproductive Biology ( at MGH, the study’s senior author. “Although these oocytes derived from marrow cells don’t appear competent, at least thus far, to make fertilizable eggs, marrow does contribute something that allows a resumption of fertility in female mice sterilized by chemotherapy.”

read more | 1798 reads

Research shows cord blood comparable to matched bone marrow
By Dross at 2007-06-10 02:55

University of Minnesota researchers report that umbilical cord blood transplants may offer blood cancer patients better outcomes than bone marrow transplants, according to an analysis of outcome data performed at the Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee.

This is the first study that directly compares matched bone marrow, which is currently considered the preferred graft, with matched and mismatched umbilical cord blood. There is considerable controversy in the medical community about which source of blood stem cells (cord blood or marrow) should be considered the “gold standard” for treatment of childhood leukemiaterm.

read more | 6961 reads

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 | 2124 reads

Bone Marrow Transplantation - Abstract of article: Comparison of long-term outcomes after allogeneic hematopoietic stem cell tra
By admin at 2006-12-11 05:52

Bone Marrow Transplantation (2006) 38, 799–805. doi:10.1038/sj.bmt.1705531; published online 30 October 2006 Bone Marrow Transplantation - Abstract of article: Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors]:Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77plusminus5% for the MSD and 67plusminus11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

read more | 1734 reads

Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG)
By Anonymous at 2006-12-01 02:08

We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144). Grade II-IV acute graft-versus-host disease (GvHD) occurred in six patients (35%).

read more | 1 comment | 2052 reads

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