Immune reconstitution following stem cell transplantation

Brink, Marcel R.M. van den; Velardi, Enrico; Perales, Miguel-Ángel

doi:10.1182/asheducation-2015.1.215

Cited by 79 publications

(61 citation statements)

References 72 publications

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“…A diverse graft may aid restoration of an advantageous thymic microenvironment in the host and enhance proper T cell selection and output. This effect possibly may be reinforced at later time points after transplantation when immunosuppression is tapered and/or discontinued in patients without GVHD, a condition that can impair immune reconstitution [3]. Regarding the impact of graft source in the analyses, another potential explanation (ie, confounding factor) for higher TREC numbers in patients receiving bone marrow compared with those receiving PBSC could be a younger recipient age in the former group.…”

Section: Discussionmentioning

confidence: 99%

“…Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for a broad spectrum of diseases, predominantly high-risk hematologic malignancies [1]. Pretransplantation conditioning regimens and subsequent immunosuppressive protocols constitute risk factors for long-term humoral and cellular immunodeficiency, contributing to morbidity and mortality by post-transplantation infection, disease relapse, or secondary malignancy [2,3]. To quantitatively and qualitatively restore immune competence, T cell and B cell reconstitution from primary lymphoid organs in the host are pivotal.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Törlén

Gaballa

Remberger

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning regimen and post-transplantation immunosuppression are risk factors for prolonged immunodeficiency. Nevertheless, the effects of different immunosuppressive protocols on lymphocyte output and replicative capacity have not been investigated. Here we assessed T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate versus tacrolimus/sirolimus; n = 200).Results showed that medians of TREC, KREC, and TL were not significantly different between the prophylaxis groups at any assessment time point during follow-up (24 months), but the kinetics of TREC, KREC, and TL were significantly influenced by other transplantation-related factors. Older recipient age, the use of antithymocyte globulin before graft infusion, and use of peripheral blood stem cell grafts were associated with lower TREC levels, whereas acute GVHD transiently affected KREC levels. Patients with lymphocyte excision circle levels above the median at 6 months post-transplantation had reduced transplantation-related mortality and superior 5-year overall survival (P < .05). We noticed significant T cell telomere shortening in the patient population as a whole during follow-up. Our results suggest that lymphocyte reconstitution after transplantation is not altered by different immunosuppressive protocols. This study has been registered at ClinicalTrials.gov (identifier: NCT00993343).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Törlén

Gaballa

Remberger

et al. 2019

Biology of Blood and Marrow Transplantation

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“…There are some markers for monitorization of immune reconstitution after HSCT: . Measurement of the functions (ELISPOT, intracellular cytokine measurement with flow cytometry tetramerous measurement) methods can be used (15).…”

Section: Recovery Of Adaptive Immunitymentioning

confidence: 99%

“…In currents studies, some methods showed promising results for the strengthening of immune recovery after HSCT including IL-7, keratinocyte growth factor, growth hormone, T lymphocyte precursor cultures being given to the recipient, and sex hormone ablation techniques (15).…”

Section: Recovery Of Adaptive Immunitymentioning

confidence: 99%

When Does Immune Recovery Occur After Stem Cell Transplantation?

Kadayıfçı¹

2019

J Pediatr Inf

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Hematopoietik kök hücre nakli 1950'li yıllardan bugüne kadar pek çok hastalığın tedavisinde giderek artan oranda kullanılmakta, bu tedavi yöntemiyle ilgili artçıl sorunların ve immün düzelmenin yönetilmesi konusu ise günümüzdeki araştırmaların temel odağını oluşturmaktadır. Nakil sonrası immün düzelme ise kullanılan kök hücre kaynağına, yapılan immün baskılayıcı müdahalelere, gelişen artçıl sorunlara, farklı zamanlarda iyileşme gösterebilen hücre alt tiplerine göre nakilden hemen sonra başlayıp, beş yıla kadar da uzayabilmektedir.

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“…37, 38 Early immune recovery following HCT has been studied by quantifying white cell subsets. Early immune recovery proceeds in the following order: NK cells, B cells, CD8 T cells first, followed later by CD4 T cells, plasma cells and dendritic cells.…”

Section: Section 2 Immune Reconstitution In the Laboratorymentioning

confidence: 99%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Immune Dysregulation and Pathobiology Working Group Report

Gea-Banacloche

Komanduri

Carpenter

et al. 2017

Biology of Blood and Marrow Transplantation

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Immune reconstitution following hematopoietic stem cell transplantation (HCT) beyond one year is not completely understood. Many transplant recipients who are free of graft versus host disease (GVHD) and not receiving any immunosuppression more than a year after transplant seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, two large registry studies over the last two decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD. Research on this topic is particularly challenging for several reasons. First, there are not enough long term follow-up clinics able to measure even basic immune parameters late after HCT. Second, the correlation between laboratory measurements of immune function and infections is not well known. Third, accurate documentation of infectious episodes is notoriously difficult. Finally, it is unclear what measures can be implemented to improve the immune response in a clinically relevant way. A combination of long-term multicenter prospective studies that collect detailed infectious data and store samples as well as a national or multi-national registry of clinically significant infections (e.g., vaccine-preventable severe infections, opportunistic infections) could begin to address our knowledge gaps. Obtaining samples for laboratory evaluation of the immune system should be both calendar driven and eventdriven. Attention to detail and standardization of practices regarding prophylaxis, diagnosis and definitions of infections would be of paramount importance to obtain clean, reliable data. Laboratory studies should specifically address the neogenesis, maturation and exhaustion of the adaptive immune system and in particular how these are influenced by persistent alloreactivity, inflammation and viral infection. Ideally, some of these long-term prospective studies would collect information on long-term changes in the gut microbiome and their influence on immunity. Regarding enhancement of immune function, prospective measurement of the response to vaccines late after HCT in a variety of clinical settings should be undertaken to better understand the benefit as well as the limitations of immunizations. The role of intravenous immunoglobulin is still not well defined, and studies to address it should be encouraged.

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Immune reconstitution following stem cell transplantation

Cited by 79 publications

References 72 publications

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

When Does Immune Recovery Occur After Stem Cell Transplantation?

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Immune Dysregulation and Pathobiology Working Group Report

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