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Biology of Blood and Marrow... Feb 2016Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The... (Review)
Review
Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The occurrence of complications and mortality after allo-HCT is, however, still high and is strongly associated with immune reconstitution (IR). Therefore, detailed information on IR through immunomonitoring is crucial to improve survival chances after HCT. To date, information about the reconstituting immune system after allo-HCT in pediatric patients is mostly derived from routine standard-of-care measurements. More profound knowledge on IR may provide tools to better predict and modulate adverse reactions and, subsequently, improve survival chances. Here, we provide an overview of IR (eg, immune cell subsets and circulating chemokines/cytokines) after allo-HCT in children, taking into account different cell sources and serotherapy, and discuss strategies to enhance immunomonitoring. We conclude that available IR data after allo-HCT contain limited information on immune cell families (mostly only generic T, B, and NK cells), which would improve with more detailed information on reconstituting cell subsets or effector cell functionality at earlier time points (<1 month). In addition, secretome data (eg, multiplex cytokine/chemokine profiles) could add to the understanding of IR mechanisms and cell functionality and may even provide (early) biomarkers for individual disease outcome, such as viral reactivity, graft-versus-host disease, or graft-versus-leukemia. The present data and suggestions for more detailed, standardized, and harmonized immunomonitoring in future (pediatric) allo-HCT studies will pave the path to "precision transplantation:" an individualized HCT approach (including conditioning), based on detailed information on IR and biomarkers, aiming to reduce transplantation related mortality and relapse, and subsequently improve survival chances.
Topics: Biomarkers; Child; Child, Preschool; Hematopoietic Stem Cell Transplantation; Humans; Immunization, Passive; Risk Factors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 26341398
DOI: 10.1016/j.bbmt.2015.08.028 -
Leukemia Oct 2006Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who... (Review)
Review
Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease (GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells.
Topics: Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 16871276
DOI: 10.1038/sj.leu.2404335 -
Frontiers in Immunology 2019B cell reconstitution after hematopoietic stem cell transplantation (HSCT) is variable and influenced by different patient, donor, and treatment related factors. In this... (Review)
Review
B cell reconstitution after hematopoietic stem cell transplantation (HSCT) is variable and influenced by different patient, donor, and treatment related factors. In this review we describe B cell reconstitution after pediatric allogeneic HST, including the kinetics of reconstitution of the different B cell subsets and the development of the B cell repertoire, and discuss the influencing factors. Observational studies show important roles for stem cell source, conditioning regimen, and graft vs. host disease in B cell reconstitution. In addition, B cell recovery can play an important role in post-transplant infections and vaccine responses to encapsulated bacteria, such as pneumococcus. A substantial number of patients experience impaired B cell function and/or dependency on Ig substitution after allogeneic HSCT. The underlying mechanisms are largely unresolved. The integrated aspects of B cell recovery after HSCT, especially BCR repertoire reconstitution, are awaiting further investigation using modern techniques in order to gain more insight into B cell reconstitution and to develop strategies to improve humoral immunity after allogeneic HSCT.
Topics: Age Factors; B-Lymphocytes; Child, Preschool; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immune Reconstitution; Infant; Infections; Transplantation Conditioning; Transplantation, Homologous; Vaccination; Vaccines
PubMed: 31031769
DOI: 10.3389/fimmu.2019.00782 -
Acta Haematologica 2020AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell... (Review)
Review
AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in myeloma. This application has evolved significantly over the past three decades. This review provides a comprehensive assessment of eligibility criteria, stem cell collection, and mobilization strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies as well as long-term outcome with respect to survival, hematologic response and relapse as well as organ responses following stem cell transplantation. Continued efforts to refine patient selection and management, and incorporate novel anti-plasma cell agents in combination or sequentially to further improve outcomes in AL amyloidosis are also discussed.
Topics: Combined Modality Therapy; Disease Management; Hematopoietic Stem Cell Mobilization; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Myeloablative Agonists; Organ Specificity; Peripheral Blood Stem Cell Transplantation; Postoperative Care; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome
PubMed: 32248194
DOI: 10.1159/000506498 -
Hematology. American Society of... Dec 2021Excellent outcomes in hematopoietic cell transplantation (HCT) from HLA-identical siblings, improvements in conditioning regimens, novel graft-versus-host disease...
Excellent outcomes in hematopoietic cell transplantation (HCT) from HLA-identical siblings, improvements in conditioning regimens, novel graft-versus-host disease prophylaxis, and the availability of alternative donors have all contributed to the increased applicability and acceptability of HCT for sickle cell disease (SCD). In young children with symptomatic SCD with an available HLA-identical related donor, HCT should be carefully considered. HCT from alternative donors is typically undertaken only in patients with severe symptoms, causing or likely to cause organ damage, and in the context of clinical trials. Patients undergoing HCT for SCD require careful counseling and preparation. They require careful monitoring of unique organ toxicities and complications during HCT. Patients must be prospectively followed for a prolonged time to determine the long-term outcomes and late effects of HCT for SCD. Thus, there is a need for a universal, longitudinal clinical registry to follow patients after HCT for SCD in conjunction with individuals who do not receive HCT to compare outcomes. Antibody-based conditioning and ex-vivo umbilical cord blood expansion are likely to improve the availability and acceptability of HCT. In addition, new disease-modifying drugs and the emerging option of the autologous transplantation of gene-modified hematopoietic progenitor cells are likely to expand the available therapeutic options and make decision-making by patients, physicians, and caregivers even more complicated. Future efforts must also focus on determining the impact of socioeconomic status on access to and outcomes of HCT and the long-term impact of HCT on patients, families, and society.
Topics: Anemia, Sickle Cell; Clinical Decision-Making; Donor Selection; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning
PubMed: 34889368
DOI: 10.1182/hematology.2021000251 -
Molecular Therapy : the Journal of the... May 2018
Topics: Bone Marrow Transplantation; Stem Cells; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous
PubMed: 29685383
DOI: 10.1016/j.ymthe.2018.04.011 -
Journal of Global Oncology Dec 2018Use of haploidentical (haplo) donors for hematopoietic cell transplantation (HCT) has significantly increased in the last decade. The major advantage with this strategy... (Review)
Review
Use of haploidentical (haplo) donors for hematopoietic cell transplantation (HCT) has significantly increased in the last decade. The major advantage with this strategy is universal availability and faster acquisition of the donor, along with affordability and provision of immunotherapy in post-transplantation period. Historically, haplo-HCT was associated with compromised outcomes because of high rates of graft-versus-host disease and graft failure, but after the development of a post-transplantation high-dose cyclophosphamide strategy, which results in selective T-cell depletion, these issues have been addressed to a large extent. Nevertheless, graft failure, high treatment-related mortality due to graft-versus-host disease, infections, delayed immune reconstitution, and disease relapse remain significant concerns. As the experience with haplo-HCTs grows, the clinical outcomes are becoming more at par with those seen with fully matched unrelated donor allogeneic HCTs.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning; Transplantation, Haploidentical
PubMed: 30521413
DOI: 10.1200/JGO.18.00130 -
Frontiers in Immunology 2020Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow... (Review)
Review
Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow failure syndromes, and primary immunodeficiencies. Early establishment of donor-derived innate and adaptive immunity following HCT is associated with improved overall survival, lower risk of infections and decreased incidence of graft failure. Immune reconstitution (IR) is impacted by numerous clinical variables including primary disease, donor characteristics, conditioning regimen, and graft versus host disease (GVHD). Recent advancements in HCT have been directed at reducing toxicity of conditioning therapy, expanding donor availability through use of alternative donor sources, and addressing morbidity from GVHD with novel graft manipulation. These novel transplant approaches impact the kinetics of immune recovery, which influence post-transplant outcomes. Here we review immune reconstitution in pediatric patients undergoing HCT for non-malignant disorders. We explore the transplant-associated factors that influence immunologic recovery and the disease-specific associations between IR and transplant outcomes.
Topics: Age Factors; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hemoglobinopathies; Humans; Immune Reconstitution; Primary Immunodeficiency Diseases; Risk Factors; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 33013851
DOI: 10.3389/fimmu.2020.01988 -
Seminars in Oncology Nursing May 2009To review the literature related to nonmyeloablative stem cell transplantation (SCT), and the unique characteristics and patient population to which it applies. (Review)
Review
OBJECTIVE
To review the literature related to nonmyeloablative stem cell transplantation (SCT), and the unique characteristics and patient population to which it applies.
DATA SOURCES
Research studies, research and clinical reviews, clinical experience.
CONCLUSION
Nonmyeloablative SCT has demonstrated effective and safe application in a heterogeneous population not otherwise eligible for an allogeneic transplantation. Although many principles are based on those of conventional myeloablative transplantation, the engraftment kinetics, patient selection, and regimen-related complications are distinct.
IMPLICATIONS FOR NURSING PRACTICE
Nurses must be knowledgeable about nonmyeloablative SCT, including the provision of individualized care for a heterogeneous population. This can include non-traditional transplant indications, elderly cancer patients, and those with comorbidities.
Topics: Bone Marrow Purging; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Oncology Nursing; Patient Selection; Safety; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 19411015
DOI: 10.1016/j.soncn.2009.03.006 -
Tidsskrift For Den Norske Laegeforening... Mar 2023Allogeneic stem cell transplantation is the only curative treatment for several malignant and non-malignant haematological diseases, and is associated with a risk of...
BACKGROUND
Allogeneic stem cell transplantation is the only curative treatment for several malignant and non-malignant haematological diseases, and is associated with a risk of serious complications. In recent years, several changes have been introduced with the aim of reducing treatment-related complications. This retrospective study reviews quality indicators for patients who underwent transplantation in the period 2015-21.
MATERIAL AND METHOD
The study included 589 adult patients who were treated with allogeneic stem cell transplantation for the first time at Oslo University Hospital in the period May 2015 to May 2021. Three two-year periods are compared using descriptive methods.
RESULTS
In the period 2015-2021, the number of first-time transplant patients per year increased from 85 to 113. One-year survival increased from 68 % in the first two-year period to 74 % in the second period and 82 % in the last period. Both acute and chronic GVHD were reduced, and one-year GVHD-free and relapse-free survival increased from 42 % to 60 % during the study period.
INTERPRETATION
Since 2015, the number of transplants has increased, while survival has improved and the risk of complications is lower.
Topics: Humans; Adult; Graft vs Host Disease; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Recurrence; Transplantation Conditioning; Treatment Outcome
PubMed: 36919291
DOI: 10.4045/tidsskr.22.0521