Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children

Koning, Coco de; Plantinga, Maud; Besseling, Paul J.; Boelens, Jaap Jan; Nierkens, Stefan

doi:10.1016/j.bbmt.2015.08.028

Cited by 79 publications

(77 citation statements)

References 112 publications

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“…However, following allo-SCT, NK cells are among the first lymphocytes to reconstitute and reach normal numbers after 1–4 months, independent of the stem cell source (17, 19, 22, 23). …”

Section: Discussionmentioning

confidence: 99%

“…At each time point, patients were considered to be “with aGVHD” or “without aGVHD” based on clinical findings. The evaluation of aGVHD was performed on a weekly basis applying the modified Keystone and NIH criteria (19, 20). All patients suffering from aGVHD, at least at one sample drawing, were included in the aGVHD group, those without any signs of aGVHD at any sampling time point were included in the group without aGVHD.…”

Section: Methodsmentioning

confidence: 99%

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Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

et al. 2016

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One of the major challenges of allogeneic stem cell transplantation (allo-SCT) is to reduce the risk of graft-versus-host disease (GVHD) while boosting the graft-versus-leukemia (GVL) effect. The reconstitution of natural killer (NK) cells following allo-SCT is of notable interest due to their known capability to induce GVL without GVHD. Here, in this study, we investigate the association between the incidence and severity of acute graft-versus-host disease (aGVHD) and the early reconstitution of NK cell subsets following allo-SCT. We analyzed 342 samples from 107 patients using flow cytometry, with a focus on immature CD56high and mature cytotoxic CD56dim NK cells. Longitudinal analysis of immune reconstitution after allo-SCT showed that the incidence of aGVHD was associated with a delayed expansion of the entire NK cell population, in particular the CD56high subset. Notably, the disturbed reconstitution of the CD56high NK cells also correlated with the severity of aGVHD.

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“…However, following allo-SCT, NK cells are among the first lymphocytes to reconstitute and reach normal numbers after 1–4 months, independent of the stem cell source (17, 19, 22, 23). …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

et al. 2016

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“…E.g., B-and T-cell counts may normalize during the first months after transplantation [47]. A comprehensive summary of data concerning lymphocyte subpopulations following allo-HSCT is presented by de Koning et al [12]. The authors state, however, that available information on the post-HSCT recovery of generic T, B and NK cells is limited by later terms (>1 month post-transplant).…”

Section: Overview Of T Cell Reconstitution Post-hsctmentioning

confidence: 99%

Time course of immune recovery and viral reactivation following hematopoietic stem cell transplantation

Pankratova¹,

Чухловин²

2016

CTT

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SummaryTotal depletion of innate and adaptive immune cell populations occurs after intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) then followed by gradual recovery of immune populations, due to progenitors derived from donor hematopoietic cells which differentiate to myeloid and lymphoid lineages. Time dynamics of immune reconstitution and differential maturation of distinct immune populations is only partially evaluated, especially, at early terms post-transplant. E.g., innate immunity is restored within 1st month after HSCT, due to rapid reconstitution of granulocytes, monocytes, and natural killer (NK) cells. Meanwhile, functional recovery of mature NK-cell subsets and blood monocytes may continue for up to 3 months.Both T-and B-lymphocyte pools are restored much slower than myelomonocytic populations. The available information on their post-HSCT immune recovery is limited, since most studies are performed at later terms (>1 month post-transplant). Absolute numbers of CD8+ T cells return to control values ca. 4 months post-HSCT, however, exhibiting a skewed repertoire of memory T lymphocytes. Recovery and maturation rates of CD4+ T cells largely depend on residual thymus function, especially, in young subjects. Hence, a naïve CD4+ T cell population in pediatric patients predominates over 6 months post-HSCT. In older persons with inactive thymopoiesis the total CD4 cell counts remain low for years after HSCT. Meanwhile, antiviral cellular immunity is active since early terms post-transplant. E.g., cytotoxic CD8+ cells specific for cytomegalovirus (CMV), or Epstein-Barr virus (EBV) rapidly expand in cases of CMV or EBV activation.Despite recovery of absolute B-cell counts by day 30 post-HSCT, their functions, i.e., antigen-specific antibody production, are reduced for months and years after HSCT, due to slow restoration of mature immune cell populations, thus resemling normal evolution of B cell hierarchy in human organism.Reactivation of herpesviruses (mostly, CMV, EBV and Herpes Simplex) is a known feature of immune deficiency. Timing of maximal herpesvirus incidence (2-3 months post-HSCT) corresponds to the period of CD8+ and CD4+ T cell functional deficiency and B cell immaturity, thus reflecting their suboptimal ability to eliminate herpesvirus-affected leukocytes. Individual terms of immune recovery after allo-HSCT depend on the patients' age, source of donor cells, acute GvHD post-HSCT etc. Vaccination response, being a potent in vivo criterion of immune recovery in post-transplant patients, is also dependent on the subjects' age and restored B cell functions. Time dynamics of specific antibody response shows that the patients with latent CMV reactivation may later exhibit a strong humoral immune response, thus making the infection self-limiting.

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“…Infections that occur during the late postengraftment period are associated with the presence and the severity of chronic GVHD, which prevents the normal recovery of cellular and humoral immunity. In addition, functional asplenia persists in patients with GVHD and in those undergoing total-body irradiation (2,3,(10)(11)(12).…”

Section: Principles Of Hsctmentioning

confidence: 99%

Brain Imaging Findings and Neurologic Complications after Allogenic Hematopoietic Stem Cell Transplantation in Children

et al. 2018

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Hematopoietic stem cell transplantation (HSCT) is the only therapy for a subset of patients with malignant and nonmalignant diseases. Central nervous system (CNS) complications continue to be an important cause of morbidity and significantly contribute to mortality after HSCT. These complications include infections, cerebrovascular lesions, therapy-induced diseases, metabolic disturbances, and post-HSCT carcinogenesis. Following HSCT, three phases can be identified on the basis of the patient's immune status: the pre-engraftment period (<30 days after HSCT), the early postengraftment period (30-100 days after HSCT), and the late postengraftment period (>100 days after HSCT). There is a distinct relationship between the patient's degree of immunodeficiency after HSCT and the incidence of various complications that may occur. Early diagnosis of CNS complications is crucial for successful management and a good prognosis, and computed tomography and magnetic resonance imaging play an important role in achieving these goals. The global increase in the use of HSCT requires radiologists to be familiar with CNS complications, their relationship to the patient's immune status, and their imaging appearances. This article describes the clinical background of HSCT; reviews the incidence, causes, and timeline of brain complications in children who underwent allogenic HSCT; and identifies the characteristic imaging findings of these disorders. RSNA, 2018.

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Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children

Cited by 79 publications

References 112 publications

Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

Relation between Acute GVHD and NK Cell Subset Reconstitution Following Allogeneic Stem Cell Transplantation

Time course of immune recovery and viral reactivation following hematopoietic stem cell transplantation

Brain Imaging Findings and Neurologic Complications after Allogenic Hematopoietic Stem Cell Transplantation in Children

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