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  • Letter to the Editor
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Reply to SB Mossad

Bone Marrow Transplantation volume 47, page 1380 (2012)Cite this article

Subjects

In his letter above, SB Mossad comments on our recent study on the clinical efficacy and safety of primary antifungal prophylaxis with posaconazole vs itraconazole in allogeneic blood and marrow transplantation.1 The author notes limitations which in his opinion significantly discredit the value of the data presented. We do not agree with Dr Mossad's comments and would like to respectfully reply:

  1. 1)

    It is correct that our study compares patient populations in two consecutive periods of time. The standards of care including protective isolation measures and availability and use of diagnostic tests did not change during the overall time-frame of <4 years for the whole series. We believe that this obvious feature of historical controls does not discredit the value of the data presented.

  2. 2)

    Our study included all consecutive adult recipients of a first allogeneic BMT with no previous history of invasive fungal disease (IFD) who received primary antifungal prophylaxis during the study period. A new transplant unit increasing from 6 to 12 single high-efficiency particulate air (HEPA)-filtered rooms for BMT became available in the summer of 2005, and our decision, to avoid a potential effect of the unit, was not to include any patients transplanted before that date (all these were itraconazole cases). Rather than a proper sample of cases to calculate from a larger group, the analysis includes everyone within the inclusion/exclusion criteria for the established time period. A potential issue might have been that with this design the study could have been underpowered to detect differences (type II error), but that was not the case, probably as a result of the high underlying event rate in itraconazole patients and the marked effect size of the change to posaconazole. We believe that the absence of a formal size calculation in this study does not discredit the value of the data presented.

  3. 3)

    The performance of thorough diagnostic algorithms to manage hematology patients at a high risk of IFD, recommended by many national and international guidelines, has been part of patient management in all recent clinical trials on antifungal management including both posaconazole registration clinical trials,2,3 and is progressively becoming an essential part of clinical practice in most, if not all, centers where the diagnostic tools are available. Beyond the ongoing need to investigate and improve the performance of diagnostic tests for particular groups of patients, we believe that the routine performance of novel diagnostics in our patients, including twice-weekly galactomannan, cannot be identified as a limitation to discredit the value of the data presented.

  4. 4)

    The definition of the primary end point (Methods section, third paragraph) clearly reads that ‘Primary end point of our analysis was the incidence of probable or proven breakthrough IFD as defined according to the 2008 criteria of the European Organization for Research and Treatment of Cancer (EORTC)’.

  5. 5)

    There was a statistical trend (P=0.06) towards most patients receiving reduced intensity conditioning in the posaconazole group, as well as a statistical trend towards a higher use of unrelated donors (39% vs 12.5%, P=0.09) and a significantly higher percentage of in vitro T-cell depletion with alemtuzumab or anti-thymocyte globulin (ATG) (39% vs 0%, P=0.003) in this same group of patients. Despite the intrinsic heterogeneity present in this and any other retrospective cohort comparisons, the populations in our study are fairly balanced in terms of factors for and against the risk of IFD, and we believe that it does not discredit the value of the data presented.

It is correct that our study compares patient populations in two consecutive periods of time. The standards of care including protective isolation measures and availability and use of diagnostic tests did not change during the overall time-frame of <4 years for the whole series. We believe that this obvious feature of historical controls does not discredit the value of the data presented.

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References

  1. Sánchez-Ortega I, Patiño B, Arnan M, Peralta T, Parody R, Gudiol C et al. Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole vs itraconazole in allogeneic blood and marrow transplantation. Bone Marrow Transplant 2011; 46: 733–739.

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  2. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007; 356: 335–347.

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  3. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356: 348–359.

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Authors and Affiliations

  1. Department of Haematology, Catalan Institute of Oncology, Barcelona, Spain

    I Sánchez-Ortega & R F Duarte

  2. Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain

    I Sánchez-Ortega

  3. Clinical Research Unit, Catalan Institute of Oncology, Barcelona, Spain

    M Encuentra

  4. Institut d’Investigaciò Biomedica de Bellvitge (Idibell), Barcelona, Spain

    R F Duarte

Authors
  1. I Sánchez-Ortega
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  2. M Encuentra
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  3. R F Duarte
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Correspondence to R F Duarte.

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Sánchez-Ortega, I., Encuentra, M. & Duarte, R. Reply to SB Mossad. Bone Marrow Transplant 47, 1380 (2012). https://doi.org/10.1038/bmt.2012.35

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