Immune reconstitution following hematopoietic stem cell transplantation using different stem cell sources

Elfeky, Reem; Lazareva, Arina; Qasim, Waseem; Veys, Paul

doi:10.1080/1744666x.2019.1612746

Cited by 36 publications

(37 citation statements)

References 145 publications

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“…Peripheral blood (PB), bone marrow (BM), or umbilical cord blood (UCB) stem cells can be utilized for HCT from either related (RD) or unrelated donors (URD). These donor sources vary in cellular composition with PB grafts having 10-fold higher T and B cells than BM grafts and single UCB grafts having 10-100-fold fewer nucleated cells compared to BM (1,4,5). The differences in graft composition impact donor IR and infectious complications following HCT.…”

Section: Stem Cell Sourcementioning

confidence: 99%

“…Recovery of immunity after HCT is influenced by various clinical factors, including primary diagnosis, donor type, stem cell source, graft manipulation, conditioning regimen (i.e., intensity of conditioning, use of irradiation, serotherapy), and pharmacologic prophylaxis, development and treatment of graft-versus-host disease (GVHD) (1,2). After HCT, establishment of donor immunity is variable and occurs in phases.…”

Section: Introductionmentioning

confidence: 99%

“…Allogeneic hematopoietic cell transplant (HCT) is a key therapeutic approach for many non-malignant hematopoietic diseases in pediatric patients, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. Effective reconstitution of donor-derived innate and adaptive immune cell number and function following HCT is critical for promoting donor cell engraftment, restoring protection against infections, and improving overall survival ( 1 , 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Bhatt

Bednarski

2020

Front. Immunol.

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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 donorderived 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.

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Section: Stem Cell Sourcementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Bhatt

Bednarski

2020

Front. Immunol.

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“…Among the graft-related variables that can influence immune reconstitution are the graft source and composition, degree of HLA-match and the cell dose (10)(11)(12). Transplantation with matched related bone marrow (BM) or peripheral blood (PB) (stem) cells is considered the standard for allo-HCT, but also matched unrelated donors (MUD) (mis)matched unrelated cord blood (CB), a haplo-identical or a mismatched family donor can be considered as alternative graft sources.…”

Section: Introductionmentioning

confidence: 99%

Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization

2020

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Hematopoietic cell transplantation (HCT) is often a last resort, but potentially curative treatment option for children suffering from hematological malignancies and a variety of non-malignant disorders, such as bone marrow failure, inborn metabolic disease or immune deficiencies. Although efficacy and safety of the HCT procedure has increased significantly over the last decades, the majority of the patients still suffer from severe acute toxicity, viral reactivation, acute or chronic graft-versus-host disease (GvHD) and/or, in case of malignant disease, relapses. Factors influencing HCT outcomes are numerous and versatile. For example, there is variation in the selected graft sources, type of infused cell subsets, cell doses, and the protocols used for conditioning, as well as immune suppression and treatment of adverse events. Moreover, recent pharmacokinetic studies show that medications used in the conditioning regimen (e.g., busulphan, fludarabine, anti-thymocyte globulin) should be dosed patient-specific to achieve optimal exposure in every individual patient. Due to this multitude of variables and site-specific policies/preferences, harmonization between HCT centers is still difficult to achieve. Literature shows that adequate immune recovery post-HCT limits both relapse and non-relapse mortality (death due to viral reactivations and GvHD). Monitoring immune parameters post-HCT may facilitate a timely prediction of outcome. The use of standardized assays to measure immune parameters would facilitate a fast comparison between different strategies tested in different centers or between different clinical trials. We here discuss immune cell markers that may contribute to clinical decision making and may be worth to standardize in multicenter collaborations for future trials.

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“…Umbilical cord blood (UCB) has proven to be an important alternative to adult sources of haematopoietic stem cells (HSC) for allogeneic transplantation, particularly for paediatric patients and for those with no suitable HLA-matched donor [1]. The use of UCB can provide outcomes equivalent to those for adult bone marrow (BM) and peripheral blood HSC for a number of indications, but the main drawbacks have been limiting cell content and higher rates of graft failure and non-relapse mortality associated with slower engraftment [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Immune reconstitution following umbilical cord blood transplantation: IRES, a study of UK paediatric patients

Girdlestone

Raymond

Shaw

et al. 2020

eJHaem

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To obtain a qualitative as well as quantitative view immune reconstitution following umbilical cord blood (UCB) transplantation of paediatric patients, we utilised a broad panel of flow cytometry markers to monitor the phenotypes of lymphoid and myeloid cells at 1‐12 months post‐transplant. Samples were received from 46 patients with a median age of 3.3 years and survival was 76% at 1 year. Monocytes were at similar or higher median levels than in adult controls at all times tested, with a high CD16+ proportion in the first 3 months. NK cells were also within adult ranges, with a CD56++ high proportion in the first 6 months. B cell recovery was seen from 2 months in most patients and T cells from 3 months, both were delayed with anti‐thymocyte globulin (ATG) treatment. CD4:CD8 ratios were high in the first 6 months, and the proportion of T cells with recent thymic emigrant and naïve phenotypes rose from 3 months. NK and plasmacytoid dendritic cell numbers remained at reduced levels in patients not surviving to 1 year. Our results can serve as a useful reference for detailed monitoring of immune reconstitution in paediatric recipients of UCB.

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Immune reconstitution following hematopoietic stem cell transplantation using different stem cell sources

Cited by 36 publications

References 145 publications

Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization

Immune reconstitution following umbilical cord blood transplantation: IRES, a study of UK paediatric patients

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