Evidence map›Paper›PMID 31131436›Full record

ArticleClinical pharmacokinetics2019

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome.

Rick Admiraal, Cornelia M Jol-van der Zijde, Juliana M Furtado Silva, Catherijne A J Knibbe, Arjan C Lankester, Jaap Jan Boelens, Goeff Hale, Aniekan Etuk, Melanie Wilson, Stuart Adams and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Trial
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  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
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  13. Allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency.Hematology. American Society of Hematology. Education Program · 2020
    Review
  14. Article
  15. Treatment of primary immunodeficiency with allogeneic transplant and gene therapy.Hematology. American Society of Hematology. Education Program · 2019
    Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Rick AdmiraalDivision of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-1512-2791
Cornelia M Jol-van der ZijdeDivision of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Juliana M Furtado SilvaBone Marrow Transplantation Department, Great Ormond Street Hospital, London, UK.
Catherijne A J KnibbeDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, University of Leiden, Leiden, The Netherlands.
Arjan C LankesterDivision of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Jaap Jan BoelensPediatric Blood and Marrow Transplantation Program, Prinses Maxima Center, Utrecht, The Netherlands.
Goeff HaleGH Developments, Oxford, UK.
Aniekan EtukDepartment of Haematology, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, UK.
Melanie WilsonDepartment of Haematology, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, UK.
Stuart AdamsDepartment of Haematology, Camelia Botnar Laboratories, Great Ormond Street Hospital, London, UK.
Paul VeysBone Marrow Transplantation Department, Great Ormond Street Hospital, London, UK.
Charlotte van KesterenDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, University of Leiden, Leiden, The Netherlands.
Robbert G M BrediusDivision of Stem Cell Transplantation, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. r.g.m.bredius@lumc.nl.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

BACKGROUND AND

objectiveAlemtuzumab (Campath

methodsA population pharmacokinetic (PK) model for alemtuzumab was developed based on a total of 1146 concentration samples from 206 patients, aged 0.2-19 years, receiving a cumulative intravenous dose of 0.2-1.5 mg/kg, and treated between 2003 and 2015 in two centers.

resultsAlemtuzumab PK were best described using a two-compartment model with a parallel saturable and linear elimination pathway. The linear clearance pathway, central volume of distribution, and intercompartmental distribution increased with body weight. Blood lymphocyte counts, a potential substrate for alemtuzumab, did not impact clearance.

conclusionThe current practice with uniform milligram/kilogram doses leads to highly variable exposures in children due to the non-linear relationship between body weight and alemtuzumab PK. This model may be used for individualized dosing of alemtuzumab.

Indexed as

Models, BiologicalAdolescentAlemtuzumabAntineoplastic Agents, ImmunologicalBody WeightChildChild, PreschoolDose-Response Relationship, DrugFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansInfantMalePrecision MedicineProspective StudiesAlemtuzumabAntineoplastic Agents, Immunological

Identifiers

PMID31131436
PMCPMC6885503

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.