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Infections

A new time-dependent approach for assessment of the impact of invasive aspergillosis shows effect on short- but not on long-term survival of patients with AML or high-risk MDS

Bone Marrow Transplantation volume 52, pages 883–888 (2017)Cite this article

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Abstract

Invasive aspergillosis (IA) has been reported to yield high mortality rates. Patients with an unfavourable prognostic haematological disease not only have a higher probability of developing IA but are also more likely to die due to causes directly related to the underlying disease. This complexity of risk mechanisms confounds the causal interpretation of IA occurrence and mortality. Full consideration of the changing patient characteristics over time is necessary to obtain reliable estimates of the correlation of IA with mortality. We studied the effect of IA on mortality in 167 consecutive patients starting with remission–induction therapy for AML or of whom most patients continued to haematopoietic stem cell transplantation (HSCT). No standard antifungal prophylaxis was administered in the period before HSCT. Survival analyses were performed to determine risk estimates of IA for different phases of treatment before and after HSCT. Time-dependent adjustment for confounding variables was performed using Cox proportional hazards models. In 55 of 167 enroled patients, IA was diagnosed. Before HSCT, adjusted hazard ratios and 95% confidence intervals on mortality after the diagnosis of IA were 3.5 (1.7–7.5), 2.0 (0.69–5.9), 2.3 (0.79–6.8) and 0.80 (0.49–1.4) within 30 days, between 30 and 60 days, between 60 and 90 days or more than 90 days, respectively. A similar pattern was observed after HSCT. The occurrence of IA did not significantly influence the decision to follow through with HSCT. The results provide new insights in short- and long-term survival of patients diagnosed with IA. A significantly increased mortality risk was only observed in the first month after diagnosis of IA. No unfavourable association with mortality was observed in the later course of treatment. The occurrence of IA did not affect the probability of attaining HSCT in our population.

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Acknowledgements

We thank Professor Dr LG Visser for reading and critical appraisal of the pre-final version of the manuscript.

Author contributions

RP and MB initiated the study and were involved in the design. RP and PB contributed to the data collection. SC contributed to the study design and statistical analysis. All authors were actively involved in manuscript preparation and have read and approved the final manuscript.

The study, in preliminary form, was presented at the Trends in Medical Mycology Congress in Lisbon, Portugal, October 2015 (abstract number P290), and awarded with a ‘Young Investigator Award’ for author RJ van de Peppel.

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Authors and Affiliations

  1. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

    R J van de Peppel & M G J de Boer

  2. Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands

    P A von dem Borne

  3. Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

    S le Cessie

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  1. R J van de Peppel
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  2. P A von dem Borne
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  3. S le Cessie
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  4. M G J de Boer
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Correspondence to R J van de Peppel.

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van de Peppel, R., von dem Borne, P., le Cessie, S. et al. A new time-dependent approach for assessment of the impact of invasive aspergillosis shows effect on short- but not on long-term survival of patients with AML or high-risk MDS. Bone Marrow Transplant 52, 883–888 (2017). https://doi.org/10.1038/bmt.2017.71

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