scholarly journals Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry

2020 ◽  
Vol 26 (5) ◽  
pp. 1021-1024
Author(s):  
Fernando Barroso Duarte ◽  
Anna Thawanny Gadelha Moura ◽  
Vaneuza Araújo Moreira Funke ◽  
Virgílio Antônio Rensi Colturato ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Transplant ◽  
Latin American ◽  
Allogeneic Transplantation ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Transplant Registry

scholarly journals Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 752
Author(s):  
Fernando A. Oliveira ◽  
Mariana P. Nucci ◽  
Javier B. Mamani ◽  
Arielly H. Alves ◽  
Gabriel N. A. Rego ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Bone Marrow Transplant ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Icp Ms ◽  
Old Mice

This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical–chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 104 SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11–120 days), achieving a peak of intensity at 30 days, which remained stable around 108 photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation.

scholarly journals DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Stefania Trino ◽  
Pietro Zoppoli ◽  
Angelo Michele Carella ◽  
Ilaria Laurenzana ◽  
Alessandro Weisz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Allogeneic Transplantation ◽  
Hematopoietic Stem

scholarly journals G-CSF-Primed Bone Marrow As a Source of Hematopoietic Stem Cells for Allogeneic Transplantation in Malignant and Non-Malignant Hematological Disorders

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2481-2481
Author(s):  
Eucario León-Rodríguez ◽  
Patricia Guzmán-Uribe ◽  
Marcela Deffis Court ◽  
Sandra Ileana Perez-Alvarez ◽  
Monica M Rivera Franco
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Hematopoietic Stem Cells ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematopoietic Stem ◽  
Hematological Disorders

Abstract Introduction: To date, worldwide, the main source of stem cells is peripheral blood (PBSCs). However, its use has been associated with a higher incidence of graft versus host disease (GVHD) when compared with the use of bone marrow. It has been demonstrated that the fast engraftment using G-CSF-primed bone marrow as a source of stem cells, compares to that seen with PBSCs, and it is also associated with a decreased incidence of GVHD. Objective: To describe the results obtained from allogeneic, G-CSF-primed bone marrow transplantations, at INCMNSZ, from November 1998 to March 2013. Material and methods: A retrospective analysis was performed in patients who underwent allogeneic, G-CSF-primed bone marrow transplantation. Clinical characteristics, frequency of GVHD, and survival, were conducted, using the Statistical Software Package SPSS v21.0. Results: Forty-nine patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, from November 1998 to March 2013, were included. Patients (male, 63%) had a median age of 29 years (range 16-59). The patients had a following range of underlying diseases: aplastic anemia (n=15, 30.6%), myelodysplastic syndrome (n=12, 24.5%), chronic myeloid leukemia (CML, n=9, 18.4%), acute lymphoblastic leukemia (LLA, n=7, 14.3%), acute myeloid leukemia (AML, n=3, 6.1%), or others (n=3, 6.1%). Patients achieved a bilineage engraftment with a median time of 20 days (range, 11-40) for absolute neutrophil count and 15 days (range, 5-45) for platelets. Acute GVHD was observed in 4 patients (8.2%), reported as grade I and II; and 14 patients (28.6%) experienced a limited form of chronic GVHD. Nine out of 49 (18.3%) patients relapsed: CML (n=5), AML (n=1), AA (n=1), ALL (n=1), others (n=1). All patients with relapsed CML were treated with donor lymphocyte infusions, but only 2 responded. Treatment related mortality (TRM) was 8.16%, including infectious complications in 2 patients, cGVHD in one patient, and veno-oclussive disease (VOD) in one patient. Overall mortality was 26.5%; the majority of deaths (69.2%) were caused by progressive and relapsing disease. With a follow up of 43 months (0-149), the median overall survival (OS) has not been reached; however, the estimated 10-year OS is 69%. Conclusion: According to our data, it seems that G-CSF-primed bone marrow is a better source of hematopoietic stem cells for allogeneic transplantation in malignant and non-malignant hematological disorders, when compared with PBSCs, due to the similar engraftment time, and a decreased incidence and severity of acute and chronic GVHD. Nevertheless, this strategy does not appear to be valid as an approach for diseases were graft versus tumor effect (GVT) is important to eradicate the malignancy, such as in CML. Disclosures No relevant conflicts of interest to declare.

Outcome of Bone Marrow Transplantation for Myelofibrosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 170-170 ◽  
Author(s):  
Karen Ballen ◽  
Kathleen A. Sobocinski ◽  
Mei-Jie Zhang ◽  
Mukta Arora ◽  
Mary M. Horowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Survival Rates ◽  
Allogeneic Transplantation ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Karnofsky Performance Score ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Sibling Donor

Abstract Myelofibrosis is a myeloproliferative disorder characterized by splenomegaly, bone marrow fibrosis and immature white and red blood cells. Allogeneic transplantation is the only curative therapy. In this study, we analyzed the outcomes of 320 patients receiving allogeneic hematopoietic stem cell transplants for myelofibrosis between 1989 and 2002, using the databases of the Center for International Bone Marrow Transplant Research (CIBMTR), a research affiliation of the International Bone Marrow Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP). This is the largest report of transplantation for myelofibrosis. Patients received a variety of conditioning and graft versus host disease prophylaxis regimens. Most patients received ablative conditioning with either TBI (n=117) or Busulfan (n=150) and cyclophosphamide. Bone marrow was the graft source in 208 patients. 170 transplants were from an HLA-identical sibling donor, 117 from an unrelated donor (MUD), and 33 from an alternative related donor. Median ages at transplant were 45 (<1–73), 47 (1–69) and 40 (<1–65) years, respectively. Median follow up times for survivors were 41 (3–136), 48 (4–124) and 32 (7–118) months, respectively. Both early and long-term survival rates were higher after HLA-identical sibling transplantation. 100-day mortality was 22% after sibling transplants, 42% after MUD transplants, and 27% after alternative family donor transplants. Corresponding 5 year overall survival rates were 39%, 31% and 31%. In multivariate analysis of 215 adult recipients of myeloablative transplants, having an HLA-identical sibling donor, Karnofsky performance score greater than or equal to 90%, younger age, more recent date of transplantation, and absence of blasts in peripheral blood prior to transplantation correlated with better survival. Among 18 patients with all of these favorable factors, the five-year probability of survival was 81%. In conclusion, 1) allogeneic transplantation cures approximately 1/3 of patients with myelofibrosis; 2) young patients with HLA-matched sibling donors have superior survival; 3) results have improved over the last decade. Future research directions will focus on the use of nonmyeloablative conditioning regimens for myelofibrosis.

Donor-Derived Hematopoietic Stem Cells Repair the Bone Marrow Sinusoids Following Bone Marrow Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1714-1714
Author(s):  
William B. Slayton ◽  
Xiao-Miao Li ◽  
Steven M. Guthrie ◽  
Marda L. Jorgensen ◽  
John R. Wingard ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Y Chromosome ◽  
Marrow Transplant ◽  
Green Fluorescence ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Megakaryocyte Progenitors

Abstract Marrow sinusoidal capillaries provide a niche for megakaryocyte progenitors and possibly hematopoietic stem cells. We sought to determine the fate of host sinusoidal capillaries during marrow transplant. We transplanted whole bone marrow, 2000 sorted Linneg Sca-1pos c-kitpos (SKL) hematopoietic stem and progenitor cells, or single SKL cells (along with rescue marrow) from male mice expressing green fluorescent protein into lethally irradiated female C57/BL6 hosts. We used green fluorescence and the presence of the Y-chromosome to identify donor-derived cells. Sinusoidal engraftment was studied from day 5 up to 1 year post-transplant and in secondary transplants. We identified numerous donor-derived cells based on green fluorescence or presence of the Y chromosome lining the sinusoids, but it was unclear whether these cells were vascular or hematopoietic. Furthermore, we were unable to demonstrate expression of von Willebrand factor, CD31 and MECA-32 using immunohistochemistry in healthy sinusoids. We used two methods to definitively identify donor-derived endothelial cells. First, we identified these cells based on location, characteristic shape and nuclei on H&E stained sections. Serial high power fields were photographed and then the same sections were stained with X and Y FISH probes. Second, we identified donor endothelial cells based on uptake of intravenously injected Ac-LDL which was endocytosed predominantly by sinusoidal endothelial cells four hours after injection. Flushed femoral bone marrow was treated with dispase and collagenase, and disaggregated cells were lineage depleted with a standard lineage cocktail containing Mac-1 antibody. Cytospins were photographed, Ac-LDL staining cells identified, and the same cytospins were stained with X and Y FISH probes. We counted numerous donor-derived endothelial cells whether 2X106 whole bone marrow (n=6 ), 2X104 SKL cells (n=6), or single SKL cells (n=2) were transplanted. These donor-derived endothelial cells were functional based on their ability to uptake DiI AcLDL. These cells appeared adjacent to mature, donor-derived megakaryocytes, suggesting function as a niche for megakaryocyte progenitors. Furthermore, donor-derived endothelial cells were present at levels similar to hematopoietic engraftment in every animal analyzed, suggesting robust levels of repair. Single cell transplants were assessed at seven and nine months, and in secondary transplants, establishing that these cells self-renew. To determine the mechanism whereby HSC’s repair the bone marrow sinusoids, we measured the expression of stromal derived factor-1 (SDF-1) at various time points during the first two weeks post-transplant by semi-quantitative RT-PCR, ELISA, and immunohistochemistry. SDF-1 expression peaked 3 days post-transplant and was expressed primarily by damaged blood vessels. The temporal and spatial pattern of engraftment matched expression patterns of SDF-1. This study demonstrates repair of host sinusoids by donor-derived endothelial cells following transplant, with levels of reconstitution similar to that of the hematopoietic system. This repair may be mediated by expression of SDF-1 by damaged marrow vasculature. Repair of sinusoidal capillaries may be a primary role of the HSC during transplant that is necessary for successful hematopoietic engraftment.

scholarly journals 2203

2017 ◽  
Vol 1 (S1) ◽  
pp. 32-32
Author(s):  
Joseph Anderson ◽  
Kyle Hendrix ◽  
Julie Beegle ◽  
Jan A. Nolta ◽  
Mehrdad Abedi
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Genomic Dna ◽  
Marrow Transplant ◽  
Hiv Treatment ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
The Stability ◽  
Anti Hiv

OBJECTIVES/SPECIFIC AIMS: To date, only 1 documented case of an individual cured of HIV has been reported. He received an allogeneic bone marrow transplant with cells harboring an HIV-resistant genotype. To mimic this result, we have initiated a Phase I to evaluate the safety of an autologous stem cell gene therapy bone marrow transplant in HIV-related lymphoma patients. METHODS/STUDY POPULATION: The first cohort of patients will receive a 1:1 ratio of unmanipulated CD34 hematopoietic stem cells (HSC) and lentivector modified CD34 HSC expressing a combination of HIV-resistant genes and a selectable marker for cell sorting prior to transplantation. Safety of the HIV-resistant stem cells will be assessed by evaluating engraftment, expression of the anti-HIV genes, and the stability and sequence of the vector. RESULTS/ANTICIPATED RESULTS: One patient has been enrolled and transplanted with the HIV-resistant stem cells. After 1 and 2 months post-transplant, patient blood samples were received, processed for genomic DNA, analyzed by quantitative PCR (qPCR), and displayed successful engraftment of 16 and 12 vector copies per 100 cells, respectively. Expression of all anti-HIV genes was confirmed by qPCR. PCR on genomic DNA confirmed the correct sizes and sequences of the integrated vector and confirmed the successful engraftment of our gene modified cells. Currently, we are enrolling more patients into the trial. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, this therapy has the potential to change HIV treatment.

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