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Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients.

Methods

This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined.

Results

No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups.

Conclusions

Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.

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Abbreviations

ALL:

Acute lymphoblastic leukaemia

ALT:

Alanine aminotransferase

AML:

Acute myeloid leukaemia

AST:

Aspartate aminotransferase

BID:

Bis in die, twice a day

CA:

Carboplatin

CsA:

Cyclosporine A

ETO:

Etoposide

FLU:

Fludarabine

GvHD:

Graft-versus-host disease

HSCT:

Haematopoietic stem cell transplantation

JMML:

Juvenile myelomonocytic leukaemia

MAC:

Myeloablative conditioning regimen

MDS:

Myelodysplastic syndromes

MFD:

Matched family donor

mg kg BW−1 :

Milligram per kilogram bodyweight

MTX:

Methotrexate

MUD:

Matched unrelated donor

n :

Sample size

NHL:

Non-Hodgkin’s lymphoma

QD:

Quaque die, once a day

RIC:

Reduced-intensity conditioning regimen

SD:

Standard deviation

TBI:

Total body irradiation

TID:

Ter in die; three times daily

TLI:

Total lymphoid irradiation

TT:

Thiotepa

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Acknowledgements

The authors received financial support from the Stefan-Morsch-Stiftung, Birkenfeld, Germany.

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Authors and Affiliations

  1. Department I – General Paediatrics, Haematology/Oncology, Children’s Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany

    Michaela Döring, Karin Melanie Cabanillas Stanchi, Manon Queudeville, Judith Feucht, Patrick Schlegel, Peter Lang & Rupert Handgretinger

  2. Ludwig-Maximilians-University München, Dr. von Hauner’sches Kinderspital, Paediatric Haematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337, Munich, Germany

    Franziska Blaeschke & Tobias Feuchtinger

  3. Department of Paediatrics Haematology and Oncology, University Hospital Hamburg-Eppendorf, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Ingo Müller

  4. Division of Infectious Diseases, Department of Internal Medicine II, University Medical Centre Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Germany

    Werner J. Heinz

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  1. Michaela Döring
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  2. Karin Melanie Cabanillas Stanchi
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  3. Manon Queudeville
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  4. Judith Feucht
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  9. Ingo Müller
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Correspondence to Michaela Döring.

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Conflict of interest

WJH received research grants from Merck and Pfizer; serves on the speakers’ bureaus of Alexion, Astellas, Bristol-Myers Squibb, Chugai Pharma, Gilead, Janssen, MSD/Merck, and Pfizer; and received travel grants from Alexion, Astellas, MSD/Merck, Novartis, and Pfizer. All other authors declare that they have no conflicts of interest.

This retrospective analysis was performed in accordance with the declaration of Helsinki and under the waiver for retrospective anonymized studies in accordance with the institutional ethics regulations. Data were collected retrospectively, entered in a standardized case report form and anonymized. Informed consent was obtained from all individual participants included in the study or their legal representatives.

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Döring, M., Cabanillas Stanchi, K.M., Queudeville, M. et al. Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation. J Cancer Res Clin Oncol 143, 1281–1292 (2017). https://doi.org/10.1007/s00432-017-2369-7

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