Hematopoietic Cell Transplantation

2017 ◽  
Author(s):  
Fred Appelbaum
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
The United States ◽  
Hematopoietic Cell ◽  
Clinical Staging ◽  
Infection Prophylaxis ◽  
Hematopoietic Stem ◽  
Allogeneic Hct

Hematopoietic cell transplantation (HCT) can replace abnormal nonmalignant hematopoietic stem cells with cells from a healthy donor, making transplantation a potential cure for a variety of nonmalignant and malignant diseases. This review discusses the indications for HCT, source of stem cells, preparative regimen, engraftment, complications, late effects and long-term survivorship, and treatment of post-transplantation relapse. Figures show the estimated total numbers of allogeneic and autologous HCTs performed in the United States, the major histocompatibility loci on chromosome 6, an approximation of the relative intensities of various preparative regimens, the typical patterns of myeloid recovery after HCT, the description  and timing of major syndromes complicating allogeneic HCT, and erythema and desquamation associated with cutaneous acute graft versus host  disease (GVHD). Tables list estimated 3-year survival rates following HCT, probability of finding a donor for HCT, clinical staging and grading of acute GVHD, National Institutes of Health global severity score of chronic GVHD, typical approach to infection prophylaxis in allogeneic transplant recipients, and summary of Centers for Disease Control and Prevention HCT vaccine guidelines. Key words: Hematopoietic cell transplantation; HCT; Allogeneic HCT; Hematopoietic stem cell transplantation; HSCT; Diseases of the lymphohematopoietic system; Autologous HCT; Hematopoietic stem cells

scholarly journals Depletion of murine fetal hematopoietic stem cells with c-Kit receptor and CD47 blockade improves neonatal engraftment

2018 ◽  
Vol 2 (24) ◽  
pp. 3602-3607 ◽  
Author(s):  
Russell G. Witt ◽  
Bowen Wang ◽  
Quoc-Hung Nguyen ◽  
Carlo Eikani ◽  
Aras N. Mattis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Hematopoietic Stem ◽  
Kit Receptor ◽  
Key Points ◽  
Immunocompetent Mice

Key Points Fetal injection of antibodies against the c-Kit receptor and CD47 effectively depletes host HSCs in immunocompetent mice. In utero depletion of host HSCs increases long-term engraftment after neonatal hematopoietic cell transplantation.

scholarly journals In utero depletion of fetal hematopoietic stem cells improves engraftment after neonatal transplantation in mice

Blood ◽  
2014 ◽  
Vol 124 (6) ◽  
pp. 973-980 ◽  
Author(s):  
S. Christopher Derderian ◽  
P. Priya Togarrati ◽  
Charmin King ◽  
Patriss W. Moradi ◽  
Damien Reynaud ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
In Utero ◽  
Hematopoietic Cell ◽  
Hematopoietic Stem ◽  
Kit Receptor ◽  
Key Points

Key Points In utero injection of an antibody against the c-Kit receptor can effectively deplete host HSCs in mice. In utero depletion of host HSCs leads to significantly increased engraftment after neonatal congenic hematopoietic cell transplantation.

scholarly journals Mesenchymal stromal cells in hematopoietic cell transplantation

2020 ◽  
Vol 4 (22) ◽  
pp. 5877-5887
Author(s):  
Andre J. Burnham ◽  
Lisa P. Daley-Bauer ◽  
Edwin M. Horwitz
Keyword(s):  
Cell Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hematopoietic Cell Transplantation ◽  
The United States ◽  
Hematopoietic Cell ◽  
Immunomodulatory Activity ◽  
Critical Determinant ◽  
Hematopoietic Stem

Abstract Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow–derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.

Phenotype, Function, and Regulation of Migrating Hematopoietic Stem Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2680-2680
Author(s):  
Amy J. Wagers ◽  
Susan S. Prohaska ◽  
Emmanuelle Passegue ◽  
Jessica Price ◽  
Irving L. Weissman
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Cell Transplantation ◽  
Molecular Mechanisms ◽  
Hematopoietic Cell Transplantation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Cycle Regulators ◽  
Hematopoietic Stem

Abstract Hematopoiesis in adult animals is maintained by a small population of clonogenic, multipotent hematopoietic stem cells (HSC), which maintain throughout life the capacity to self-renew and to differentiate to give rise to progeny cells that ultimately generate all lineages of mature blood cells. In adult mice and humans, the majority of HSC are found in the bone marrow (BM); however, HSC are also constitutively present at low levels in the circulation. The frequency of HSC in the blood can be significantly increased through the use of “mobilizing” agents, including cytotoxic drugs and/or cytokines, which often act both to drive HSC proliferation and to induce HSC migration from the BM into the bloodstream. Yet despite the increasingly common clinical exploitation of HSC in bone marrow and mobilized peripheral blood progenitor cell transplantation, both the evolutionary rationale and the molecular mechanisms that underlie the remarkable migratory capacity of HSC remain largely unknown. Therefore, to begin to elucidate the mechanisms and regulators of these events, we have used parabiotic and transplantation models to characterize normal blood-borne HSC. Our data clearly demonstrate that HSC are constitutively present in the blood of untreated mice and maintain a cell surface phenotype in the blood highly similar to their BM counterparts. Blood-borne HSC in normal mice can engraft both irradiated and non-irradiated BM niches, and subsequently are phenotypically and functionally indistinguishable from endogenous, host-type cells. These data suggest that BM homing of transplanted HSC in irradiated recipients and HSC mobilization in cytokine-treated animals likely makes use of pre-existing pathways that support the constitutive recirculation of these cells in normal animals. Finally, to extend these data and begin to uncover factors likely to play a role in stimulating HSC migration in both normal and mobilized mice, we have employed cDNA microarray technology to compare global gene expression profiles of normal and pre-migratory BM HSC, and have thus identified multiple candidate genes, including cell cycle regulators, signaling molecules, and transcription factors, that may be involved in HSC expansion or in HSC retention in and/or egress from the BM. Taken together, these findings provide significant insight into the dynamic nature and function of HSC, and may ultimately suggest novel and improved strategies for clinical hematopoietic cell transplantation.

scholarly journals Neighborhood-Poverty and Pediatric Allogeneic Hematopoietic Cell Transplantation Outcomes: A CIBMTR Analysis

Blood ◽  
2020 ◽  
Author(s):  
Kira Bona ◽  
Ruta Brazauskas ◽  
Naya He ◽  
Leslie Elaine Lehmann ◽  
Hisham Abdel-Azim ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Malignant Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
The United States ◽  
Hematopoietic Cell ◽  
Poverty Level ◽  
Neighborhood Poverty ◽  
Allogeneic Hct ◽  
Increased Risk

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States, yet their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood-poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We assembled two pediatric cohorts who received a first, allogeneic HCT from 2006-2015 at age ≤18 years; including 2053 children with malignant disease and 1696 children with non-malignant disease. Neighborhood-poverty exposure was defined a priori per U.S. Census definition as living in a high-poverty ZIP code (>=20% of persons below 100% Federal Poverty Level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS) defined as time from HCT until death from any cause. Secondary outcomes included relapse and transplant-related mortality (TRM) in malignant disease, acute and chronic GVHD, and infection in the first 100 days post-HCT. Among children transplanted for non-malignant disease, neighborhood-poverty was not associated with any HCT outcome. Among children transplanted for malignant disease, neighborhood-poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplant outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared to those with private insurance. These data suggest opportunities for future investigation of household-level poverty exposures on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

Longitudinal Assessment of Hematopoietic Abnormalities After Autologous Hematopoietic Cell Transplantation for Lymphoma

2005 ◽  
Vol 23 (27) ◽  
pp. 6699-6711 ◽  
Author(s):  
Ravi Bhatia ◽  
Khristine Van Heijzen ◽  
Ann Palmer ◽  
Asako Komiya ◽  
Marilyn L. Slovak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Hodgkin's Lymphoma ◽  
Autologous Hct ◽  
Prospective Longitudinal ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Autologous hematopoietic cell transplantation (HCT) is being increasingly used as an effective treatment strategy for patients with relapsed or refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL) but is associated with therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) as a major cause of nonrelapse mortality. The phenomenon of hematopoietic reconstitution after autologous HCT and the role of proliferative stress in the pathogenesis of t-MDS/AML are poorly understood. Patients and Methods Using a prospective longitudinal study design, we evaluated the nature and timing of alterations in hematopoietic progenitors and telomere length after HCT in patients undergoing autologous HCT at City of Hope Cancer Center (Duarte, CA). Results A significant reduction in primitive and committed progenitors was observed before HCT compared with healthy controls. Further profound and persistent reduction in primitive progenitors but only transient reduction in committed progenitors were seen after HCT. Primitive progenitor frequency in pre-HCT marrow and peripheral-blood stem cells predicted for primitive progenitor recovery after HCT. Shortening of telomere length was observed in marrow cells early after HCT, with subsequent restoration to pre-HCT levels. Patients within this cohort who developed t-MDS/AML had reduced recovery of committed progenitors and poorer telomere recovery, possibly indicating a functional defect in primitive hematopoietic cells. Conclusion Our studies suggest that hematopoietic regeneration after HCT is associated with increased proliferation and differentiation of primitive progenitors. Increased proliferative stress on stem cells bearing genotoxic damage could contribute to the pathogenesis of t-MDS/AML. Extended follow-up of a larger number of patients is required to confirm whether alterations in progenitor and telomere recovery predict for increased risk of t-MDS/AML.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

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