Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia

Florine N J Frakking; Nannette Brouwer; Marianne D van de Wetering; Ilona Kleine Budde; Paul F W Strengers; Alwin D Huitema; Inga Laursen; Gunnar Houen; Huib N Caron; Koert M Dolman; Taco W Kuijpers

doi:10.1016/j.ejca.2008.11.036

Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia

Florine N J Frakking^*, Nannette Brouwer, Marianne D van de Wetering, Ilona Kleine Budde, Paul F W Strengers, Alwin D Huitema, Inga Laursen, Gunnar Houen, Huib N Caron, Koert M Dolman, Taco W Kuijpers

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0-12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1-4 weeks). Four patients participated multiple times. Target levels of 1.0 microg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06 microg/ml (range: 0.66-2.05 microg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25 kg, was 36.4h (range: 23.7-66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective.

Original language	English
Pages (from-to)	505-12
Number of pages	8
Journal	European Journal of Cancer
Volume	45
Issue number	4
DOIs	https://doi.org/10.1016/j.ejca.2008.11.036
Publication status	Published - Mar 2009

Keywords

Antineoplastic Agents/adverse effects
Child
Child, Preschool
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Infant
Infant, Newborn
Male
Mannose-Binding Lectin/adverse effects
Neutropenia/blood
Patient Selection
Prospective Studies

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10.1016/j.ejca.2008.11.036

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Frakking, F. N. J., Brouwer, N., van de Wetering, M. D., Budde, I. K., Strengers, P. F. W., Huitema, A. D., Laursen, I., Houen, G., Caron, H. N., Dolman, K. M., & Kuijpers, T. W. (2009). Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia. European Journal of Cancer, 45(4), 505-12. https://doi.org/10.1016/j.ejca.2008.11.036

@article{3a22bf46958c4790a2e033c40a5f0ddd,

title = "Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia",

abstract = "Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0-12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1-4 weeks). Four patients participated multiple times. Target levels of 1.0 microg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06 microg/ml (range: 0.66-2.05 microg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25 kg, was 36.4h (range: 23.7-66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective.",

keywords = "Antineoplastic Agents/adverse effects, Child, Child, Preschool, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Infant, Infant, Newborn, Male, Mannose-Binding Lectin/adverse effects, Neutropenia/blood, Patient Selection, Prospective Studies",

author = "Frakking, {Florine N J} and Nannette Brouwer and {van de Wetering}, {Marianne D} and Budde, {Ilona Kleine} and Strengers, {Paul F W} and Huitema, {Alwin D} and Inga Laursen and Gunnar Houen and Caron, {Huib N} and Dolman, {Koert M} and Kuijpers, {Taco W}",

year = "2009",

month = mar,

doi = "10.1016/j.ejca.2008.11.036",

language = "English",

volume = "45",

pages = "505--12",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

number = "4",

}

Frakking, FNJ, Brouwer, N, van de Wetering, MD, Budde, IK, Strengers, PFW, Huitema, AD, Laursen, I, Houen, G, Caron, HN, Dolman, KM & Kuijpers, TW 2009, 'Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia', European Journal of Cancer, vol. 45, no. 4, pp. 505-12. https://doi.org/10.1016/j.ejca.2008.11.036

TY - JOUR

T1 - Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia

AU - Frakking, Florine N J

AU - Brouwer, Nannette

AU - van de Wetering, Marianne D

AU - Budde, Ilona Kleine

AU - Strengers, Paul F W

AU - Huitema, Alwin D

AU - Laursen, Inga

AU - Houen, Gunnar

AU - Caron, Huib N

AU - Dolman, Koert M

AU - Kuijpers, Taco W

PY - 2009/3

Y1 - 2009/3

N2 - Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0-12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1-4 weeks). Four patients participated multiple times. Target levels of 1.0 microg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06 microg/ml (range: 0.66-2.05 microg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25 kg, was 36.4h (range: 23.7-66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective.

AB - Mannose-binding lectin (MBL)-deficient children with cancer may benefit from substitution of the innate immune protein MBL during chemotherapy-induced neutropaenia. We determined the safety and pharmacokinetics of MBL substitution in a phase II study in MBL-deficient children. Twelve MBL-deficient children with cancer (aged 0-12 years) received infusions of plasma-derived MBL once, or twice weekly during a chemotherapy-induced neutropaenic episode (range: 1-4 weeks). Four patients participated multiple times. Target levels of 1.0 microg/ml were considered therapeutic. In total, 65 MBL infusions were given. No MBL-related adverse reactions were observed, and the observed trough level was 1.06 microg/ml (range: 0.66-2.05 microg/ml). Pharmacokinetics were not related to age after correction for body weight. The half-life of MBL, for a child of 25 kg, was 36.4h (range: 23.7-66.6h). No anti-MBL antibodies were measured 4 weeks after each MBL course. Substitution therapy with MBL-SSI twice weekly was safe and resulted in trough levels considered protective.

KW - Antineoplastic Agents/adverse effects

KW - Child

KW - Child, Preschool

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Mannose-Binding Lectin/adverse effects

KW - Neutropenia/blood

KW - Patient Selection

KW - Prospective Studies

U2 - 10.1016/j.ejca.2008.11.036

DO - 10.1016/j.ejca.2008.11.036

M3 - Article

C2 - 19121580

SN - 0959-8049

VL - 45

SP - 505

EP - 512

JO - European Journal of Cancer

JF - European Journal of Cancer

IS - 4

ER -

Safety and pharmacokinetics of plasma-derived mannose-binding lectin (MBL) substitution in children with chemotherapy-induced neutropaenia

Abstract

Keywords

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