Multivariate analyses of immune reconstitution in children after allo-SCT: risk-estimation based on age-matched leukocyte sub-populations

Koenig, Melanie; Huenecke, Sabine; Salzmann‐Manrique, Emilia; Esser, Ruth; Quaritsch, R; Steinhilber, Dieter; Radeke, Heinfried H.; Martin, Hans; Bader, Peter; Klingebiel, Thomas; Schwabe, Dirk; Schneider, Gisbert; Lehrnbecher, Thomas; Orth, Andreas; Koehl, Ulrike

doi:10.1038/bmt.2009.204

Cited by 24 publications

(32 citation statements)

References 32 publications

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“…We have previously created uni-and multivariate predictive models for complications after allo-SCT based on larger immune subpopulations. 4,62 These models may be improved by the incorporation of mDCs and pDCs as additional predictors. Ultimately, joint longitudinal and time-toevent models may provide dynamic complication prediction using multiple immune subpopulations.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Relapse-free survival and GVHD severity have been linked to the speed of immune recovery as well as absolute cell counts in peripheral blood (PB) for various major immune subpopulations. 4 DCs are potent APCs that link and mediate the innate and the adaptive immune systems. [5][6][7] Although their importance in the healthy immune system and a variety of diseases is well established, their role in the reconstituting immune system after allo-SCT for leukaemia has not yet been fully elucidated, especially in children.…”

Section: Introductionmentioning

confidence: 99%

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Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation

Elze

Ciocârlie

Heinze

et al. 2014

Bone Marrow Transplant

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DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age-and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/μL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P = 0.035), whereas high pDC/μL PB up to day 60 are associated with higher risk of relapse (P o 0.001). The time-trend of DCs/μL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P o0.001) and pDCs (P = 0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P = 0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation

Elze

Ciocârlie

Heinze

et al. 2014

Bone Marrow Transplant

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“…After infusion, patients received immune monitoring as previously described. 8 Furthermore, a semiquantitative PCR approach, based on the amplification of shorttandem-repeat markers, was used for chimerism analyses. 9 Unless otherwise cited, obtained data are expressed as mean ± s.d.…”

Section: Total Number Of Cellsmentioning

confidence: 99%

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Rettinger

Bönig

Wehner

et al. 2013

Bone Marrow Transplant

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Haploidentical hematopoietic SCT is an established treatment for high-risk leukemia in patients lacking a HLA-identical donor, and is also being evaluated for refractory solid tumors.The therapeutic success of any SCT for malignant disease is limited by relapse. Impending relapse can be treated by DLI, but DLI is of limited value when initiated during overt relapse. 1 Moreover, the high T-cell doses required for DLI pose a risk of severe GVHD, specifically in the haploidentical setting.

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“…A more sophisticated method involved forming an ellipsoid reference domain for the normal values of a combination of three lymphocyte subtypes, and classifying people into high- and low-risk groups. Those in the low-risk group had a higher chance of survival [184].…”

Section: Immunologymentioning

confidence: 93%

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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Multivariate analyses of immune reconstitution in children after allo-SCT: risk-estimation based on age-matched leukocyte sub-populations

Cited by 24 publications

References 32 publications

Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation

Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

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