Successful engraftment of blood derived normal hemopoietic stem cells in chronic myelogenous leukemia. Studies suggest that PBSCT has a better outcome in terms of the number of hematopoietic stem cell (CD34+ cells) yield. Evidence for stem cells in the peripheral blood of mice.
These stem cells are found in the bone marrow, bloodstream, or umbilical cord blood (see Question 1). In 1986 and 1987, similar reports of successful PBSCTs were documented by research groups at the University of Nebraska Medical Center,18 the Hospital Haut Leveque in Bordeaux, France,19 and the Royal Adelaide Hospital in Adelaide, Australia.20 In all of those initial PBSCT cases, stem cells were collected by multiple apheresis procedures at steady state without hematopoietic growth factor mobilization treatment. The significantly greater number of T cells contained in PB stem-cell allografts together with a 3-fold greater percentage of natural killer cells are believed to be associated with a more pronounced GVL effect, although clinical GVL data of various randomized trials, as mentioned previously, are not conclusive. The clinical outcome of stem-cell transplantation is in part determined by the cellular composition of the stem-cell graft. Search for other works by this author on: Deoxyribonucleic acid synthesizing cells in peripheral blood of normal human beings. Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. In the early 1970s, a first attempt at M. D. Anderson Cancer Center of collecting colony-forming stem cells by continuous-flow apheresis was successful,10 thus laying the foundation for clinical PBSCT as an equivalent to BMT, albeit apheresis-derived stem cell yield was still significantly inferior to that of multiple BM aspirations. The unexpected initial finding of similar acute GVHD rates after allogeneic BMT and PBSCT prompted the design of randomized prospective clinical trials. In the 1950s, the discovery of dividing, nonleukemic DNA-synthesizing cells in peripheral blood (PB) suggested the existence of a small number of circulating cells of “multipotential character.”1 Indirect evidence of the migration of stem cells via PB was first demonstrated in so-called shielding experiments, in which, after lethal total body irradiation, stem cells from shielded hematopoietic tissue areas entered the circulating blood and subsequently repopulated the irradiated BM (Figure 1B).2 Postradiation parabiosis experiments,3 followed later by cross-circulation experiments in large animals,4 provided clear evidence that circulating stem cells were capable of reconstituting an entire lymphohematopoietic system after myeloablative treatment (Figure 1C). The logical next step was to harvest white blood cells and, among them, putative stem cells to reconstitute lymphohematopoietic function in myeloablated BM (Figure 1D). There was trilineage engraftment without GVHD. However, there were no significant differences in overall survival or leukemia-free survival between the BMT and PBSCT groups at the 3-year follow-up. wrote the manuscript; and E.F. provided archival material and documentation. Eventually, molecular evidence revealed that donor-derived multipotent stem cells transplanted into a conditioned recipient could permanently generate an entire lymphohematopoietic system. The allogeneic transplantation setting, therefore, provided definite clinical proof that hematopoietic progenitor cells mobilized into PB and harvested by apheresis can generate a complete and sustained lymphohematopoietic system. IBMTR Statistical Center of the International Bone Marrow Transplant Registry, Medical College of Wisconsin, Milwaukee WI, USA; EBMT, Kiel, Germany. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. When it is time to transplant the cells, doctors infuse them into the bloodstream. By mobilizing preferential T helper 2-inducing dendritic cells, the cytokines IL-4 and IL-10 are produced, which are less inflammatory and, therefore, are associated with diminished GVHD-inducing ability.55, Cell subsets that are implicated in the GVL effect include CD4+ and CD8+ T cells, and natural killer cells.
Four years later, another single-case report on allogeneic stem-cell transplantation was published by researchers at Nottingham University Hospital in the United Kingdom.41 This time, G-CSF–mobilized stem cells were transplanted into an HLA-identical sibling. Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Limited potential of circulating haemopoietic stem cells. Stem cells are cells that give rise to the blood cellsred blood cells that carry oxygen, white blood cells that help the body to fight infections, and platelets that help make the blood clot. The benefit of greater survival rates was observed primarily in patients with more advanced malignancy. At the time of this writing, patient outcome results have not been released. Data were presented showing that, compared with BM allografts, the 50-fold greater number of CD14+ monocytes and monocyte progenitors contained in G-CSF–mobilized PB stem-cell allografts had a suppressive effect on donor T cells.54 G-CSF mobilization treatment was also found to have an immunomodulatory effect on the graft. These cells are harvested by a type of filtration and then preserved, usually by freezing, and finally given to the recipient after he or she has received intensive treatment. Recombinant human granulocyte colony-stimulating factor can mobilize sufficient amounts of peripheral blood stem cells in healthy volunteers for allogeneic transplantation. Contribution: M.K. The total amount of mononuclear cells transfused was 5.8 × 1010/kg recipient body weight. Data from the NMDP show an overall rate of 0.6% serious adverse events attributed to stem-cell mobilization treatment and collection.30. Stem cell migration between BM and PB. For a detailed review of the historical events leading to the clinical introduction of UCB transplantation, and major follow-up studies, we refer to Eliane Gluckman's paper published in 2009.46. Clinical findings of an EBMT-initiated prospective randomized trial51 that involved 350 patients with standard-risk leukemia turned out to have a somewhat different outcome: the incidence of grades II-IV acute GVHD was found to be significantly greater in patients who underwent PBSCT. 3102 Investigators. The same blood-forming cells that are found in bone marrow are also found in the circulating (peripheral) blood. For PBSCT to be accepted as a mainstream treatment modality, strategies to temporarily increase PB stem-cell concentration had to be developed. According to the Center for International Blood and Marrow Transplant Research database, 98% of autologous stem-cell transplantations performed between 2002 and 2006 in patients who were older than 20 years were blood-derived. In 2001, a randomized multicenter trial50 on 172 patients that involved the Fred Hutchinson Cancer Research Center and the University of Washington Hospital in Seattle, the City of Hope Medical Center in Duarte, CA, and Stanford University Hospital in California came to the following conclusions: Recovery of neutrophils and platelets was faster in patients who underwent PBSCT. In addition, there was a hesitance to expose healthy stem-cell donors to cytokine treatment for stem cell mobilization. Healthy donors were initially excluded from donating G-CSF–mobilized hematopoietic stem cells primarily because of concerns about triggering lymphohematopoietic malignancies in genetically predisposed healthy sibling donors.
It has been 25 years since peripheral blood stem cell transplantation (PBSCT) was introduced as a transplant modality. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle.
One may speculate that each individual white blood cell transfusion did not contain a sufficient amount of hematopoietic progenitor cells to enable engraftment. If you are considering donating bone marrow instead of PBSCs check out the possible risks of donating bone marrow. However, in pediatric patients BM and umbilical cord blood (UCB) are the predominant unrelated stem-cell sources. Whereas the molecular cloning and clinical development of G-CSF initially focused on ameliorating the side effects of chemotherapy-induced cytopenia, it soon became obvious that G-CSF also expanded the circulating hematopoietic stem-cell pool by mobilizing CD34+38− hematopoietic progenitor cells from extravascular BM sites to PB.22 In 1988, 2 stem-cell mobilization studies in patients at the Dana-Farber Cancer Institute in Boston, MA,23 and at Royal Melbourne Hospital in Australia24 were published. Follow-up studies showed a mobilization advantage of G-CSF over GM-CSF,25 and today G-CSF is considered the gold standard of stem-cell mobilization treatment. This anniversary, therefore, marks the first clinical evidence that circulating hematopoietic stem cells can completely and permanently regenerate a lymphohematopoietic system after myeloablative treatment. In 1989, the first attempt to transplant nonmobilized, T-cell–depleted PB stem cells into a HLA-identical sibling at the University of Nebraska Medical Center in Omaha was made.40 There was early and exclusively donor-derived hematopoietic engraftment. Even more fundamental and beyond transplant aspects, the capability of hematopoietic blood stem cells to regenerate and maintain equal cellular concentration throughout all marrow spaces in the human body attributes to them a homeostatic function that had until then never been shown before in a clinical setting (Figure 1A).
Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, using similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-specific antibodies. To test various clinical outcome parameters such as survival probability, engraftment characteristics, acute and chronic GVHD, relapse, and immunereconstitution in a more GVHD-prone transplantation setting, a phase 3, randomized, multicenter, prospective comparative study of G-CSF–mobilized PBSCT versus BMT with the use of HLA-compatible unrelated donors was designed. According to the NMDP and its Be the Match Registry, 76% of adult unrelated donors, that is > 3100, donated G-CSF–mobilized PB stem cells. Stem cell migration occurs via circulating blood. Stem-cell collection data on 1488 G-CSF mobilized donors reported to the International Bone Marrow Transplant Registry and European Group for Blood and Marrow Transplantation (EBMT) revealed a comparable safety profile to BM harvesting.28 A 2008 conference report on clinical and ethical issues of using hematopoietic growth factors in healthy stem-cell donors29 gave a state-of-the-art insight into the safety of G-CSF mobilization treatment, and came to the following conclusions: Severe but rare side effects of G-CSF mobilization treatment, including splenic rupture and sickle cell crisis, have been reported.
In 1998, the results of the first multicenter trial of the EBMT on 70 patients confirmed those early observations of similar incidence rates of moderate to severe acute GVHD and transplantation-related mortality between patients who underwent PBSCT and patients who underwent BMT.47 Randomized trials, either multicenter48 or single center,49 followed.
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