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Post-Transplant Events

A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT

Bone Marrow Transplantation volume 43, pages 553–561 (2009)Cite this article

Abstract

We compared the efficacy and safety of empirical plus PCR-based vs empirical liposomal amphotericin B treatment after Allo-SCT. Allo-SCT recipients were randomized to receive either PCR-based preemptive therapy (group A; n=198) or empirical antifungal therapy (group B; n=211) with liposomal amphotericin B. In group A, therapy was started after one positive PCR result or after 120 h of febrile neutropenia refractory to broad-spectrum antibacterial therapy. In group B, liposomal amphotericin B was started after 120 h of refractory febrile neutropenia. Demographic and clinical characteristics were well balanced. A total of 112 (57.1%) patients in group A and 76 (36.7%) patients in group B received antifungal therapy (P<0.0001). Twelve patients in group A and 16 patients in group B developed proven invasive fungal infection (IFI). Survival curves showed better survival until day 30 when close PCR monitoring was performed (mortality 1.5 vs 6.3%; P=0.015), but there was no difference at day 100. At day 100, no difference was observed in the incidence of IFI (primary end point) and survival between the two arms. Further studies are required to assess the benefit of using PCR in patients after SCT.

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Acknowledgements

This study was supported by unrestricted grants from Gilead Sciences GmbH, Martinsried, Germany, and Swedish Orphan AB (Gilead Inc.). Christoph Müller-Löbnitz, Forchheim, Germany, helped to prepare the manuscript. We thank Lothar Kanz, Tuebingen, Germany, for his support for this study and Marius Horger (Tuebingen) for reviewing radiological examinations.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Internal Medicine II, Eberhard-Karls-University, Tuebingen, Germany

    H Hebart, N Stenger & T Mayer

  2. Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    L Klingspor

  3. Children's University Hospital III, Frankfurt a. Main, Germany

    T Klingebiel

  4. Department of Internal Medicine II, Bayerische Julius-Maximilians Universität, Wuerzburg, Germany

    J Loeffler & H Einsele

  5. Department of Transplantation Surgery, Karolinska, University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    J Tollemar

  6. Hematology Center, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

    P Ljungman

  7. Department of Bone Marrow Transplantation, Internal Medicine V, North Hospital, Nuernberg, Germany

    H Wandt & K Schaefer-Eckart

  8. Division of Pediatric Hematology, Medical University of Graz, Graz, Austria

    H J Dornbusch

  9. Institute for Medical Information Processing, Eberhard-Karls-University, Tuebingen, Germany

    C Meisner & C Engel

  10. Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden

    O Ringden

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  1. H Hebart
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  2. L Klingspor
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Correspondence to H Hebart.

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Conflict of interest

Hermann Einsele declares that he has received research support for performing this study from Gilead. All decisions regarding the study, including the premature termination, were made independently by the investigators and were not influenced by the sponsor. Per Ljungman declares that he has no conflict of interest during the design of the study. Later, he had been the chair of the DSMB for the AmBiload study sponsored by Gilead. All other authors declare no conflicts of interest.

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Hebart, H., Klingspor, L., Klingebiel, T. et al. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant 43, 553–561 (2009). https://doi.org/10.1038/bmt.2008.355

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