The Impact of Early Viral Infections and Graft‐Versus‐Host Disease on Immune Reconstitution Following Paediatric Stem Cell Transplantation

Olkinuora, Helena; Willebrand, E von; Kantele, Jussi M.; Vainio, Olli; Talvensaari, Kimmo; Saarinen-Pihkala, UM; Siitonen, Sanna; Vettenranta, Kim

doi:10.1111/j.1365-3083.2011.02530.x

Cited by 37 publications

(33 citation statements)

References 48 publications

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“…It is important to note however that, in addition to age and TCD, the presence of GVHD also significantly hampers immune reconstitution via direct effects on the thymus [57,58,59], as well as the immunosuppressive drugs required for treatment of GVHD [60,61,62,63,64]. Although TCD impacts immune reconstitution leading to higher infection related deaths, GVHD in conventional grafts similarly leads to increased mortality.…”

Section: Impact Of T-cell Depletion On Engraftment and Immune Recomentioning

confidence: 99%

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Hobbs

Perales

2015

JCM

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Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion.

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Section: Impact Of T-cell Depletion On Engraftment and Immune Recomentioning

confidence: 99%

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Hobbs

Perales

2015

JCM

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“…However, this has rarely been performed. 10 Little is known about post-transplant reconstitution kinetics of human peripheral blood CD19…”

Section: Introductionmentioning

confidence: 99%

Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT

Mensen

Jöhrens

Anagnostopoulos

et al. 2014

Blood

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Key Points• Donor T-cell infiltration of the bone marrow is associated with impaired B-cell immunity after allogeneic HSCT.• Quantification of k-deleting recombination excision circles as a biomarker for bone marrow B-cell output in different clinical episodes.B-cell immune dysfunction contributes to the risk of severe infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed B-cell regeneration is found in patients with systemic graft-versus-host disease (GVHD) and is often accompanied by bone marrow (BM) suppression. Little is known about human BM GVHD. We analyzed the reconstitution kinetics of B-cell subsets in adult leukemic patients within 6 months after allo-HSCT. B-cell deficiency already existed before transplant and was aggravated after transplant. Onset of B-cell reconstitution characterized by transitional B-cell recovery occurred either early (months 2-3) or late (from month 6 on) and correlated highly positively with reverse transcription-polymerase chain reaction quantified numbers of k-deleting recombination excision circles (KRECs). Delayed recovery was associated with systemic acute GVHD and full-intensity conditioning therapy. Histological analysis of BM trephines revealed increased T-cell infiltration in late recovering patients, which was associated with reduced numbers of osteoblasts. Functionally, late recovering patients displayed less pneumococcal polysaccharide-specific immunoglobin M-producing B cells on ex vivo B-cell activation than early recovering patients. Our results provide evidence for acute BM GVHD in allo-HSCT patients with infiltrating donor T cells and osteoblast destruction. This is associated with delayed B-cell reconstitution and impaired antibody response. Herein, KREC appears suitable to monitor BM B-cell output after transplant. (Blood. 2014;124(6):963-972)

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“…The PD target for linezolid is a maximised ratio of AUC:MIC [191]. To our knowledge there are no published population PK studies of linezolid in children, only a non-compartmental PK analysis [79].…”

Section: Infectious Diseasesmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

Barker

Germovsek²,

Hoare³

et al. 2014

Advanced Drug Delivery Reviews

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Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose–concentration–effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.

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The Impact of Early Viral Infections and Graft‐Versus‐Host Disease on Immune Reconstitution Following Paediatric Stem Cell Transplantation

Cited by 37 publications

References 48 publications

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

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