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Clinical Trial
. 2023 Jan;37(1):72-78.
doi: 10.1038/s41375-022-01768-x. Epub 2022 Dec 12.

Invasive fungal diseases impact on outcome of childhood ALL - an analysis of the international trial AIEOP-BFM ALL 2009

Thomas Lehrnbecher #  1 , Andreas H Groll #  2 , Simone Cesaro  3 , Julia Alten  4 , Andishe Attarbaschi  5 , Draga Barbaric  6 , Nicole Bodmer  7 , Valentino Conter  8 , Shai Izraeli  9 , Georg Mann  5 , Anja Möricke  4 , Felix Niggli  7 , Martin Schrappe  4 , Jan Stary  10 , Ester Zapotocka  11 , Martin Zimmermann  12 , Sarah Elitzur  9
Affiliations
Clinical Trial

Invasive fungal diseases impact on outcome of childhood ALL - an analysis of the international trial AIEOP-BFM ALL 2009

Thomas Lehrnbecher et al. Leukemia. 2023 Jan.

Abstract

In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis.

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Conflict of interest statement

TL has received grants from Gilead Sciences, has served as consultant to Gilead Sciences, Merck/MSD, Pfizer, Astellas, AstraZeneca and Roche, and served at the speaker´s bureau of Gilead Sciences, Merck/MSD, Astellas, Pfizer and GSK. AHG has received grants from Gilead, Merck, Sharp & Dohme and Pfizer and has served as consultant to Amplyx, Astellas, Basilea, F2G, Gilead. Merck, Sharp & Dohme, Pfizer, Scynexis, and Mundipharma. SC served at the speaker´s bureau of Gilead Sciences and Pfizer. AA has received honoraria for lectures, consultancy or advisory board participation from the following companies: Jazz Pharmaceuticals, Amgen, Novartis, MSD, Jazz Pharmaceuticals, Amgen, Novartis, MSD, and Gilead. He has received compensation for travel expenses from Jazz Pharmaceuticals. MS and/or study group have received research support from SHIRE, JazzPharma, Servier, SigmaTau, Amgen, and Novartis. MS has received honoraria from Servier, Novartis, and JazzPharma.

Figures

Fig. 1
Fig. 1. Consort diagram of patients (pts) treated according to the clinical trial AIEOP-BFM 2017 and analyzed for possible, probable and proven invasive fungal disease (IFD).
*Yeast infection includes two patients with more than one yeast isolates. **Mold infection includes nine patients with more than one mold isolated. SAE severe adverse event, PcP Pneumocystis jirovecii pneumonia.
Fig. 2
Fig. 2. Invasive fungal disease (IFD) in the different treatment phases (protocol I, II, III and HR cycles, respectively) in standard (SR) and intermedium risk (MR) patients (above) and high risk (HR) patients (below).
Shown are the absolute number of possible (blue), probable and proven yeast (orange) and probable/proven mold (grey) infections (Y axis). The percentages refer to the total number of IFDs in the respective risk groups (SR/MR and HR).
Fig. 3
Fig. 3. Cumulative incidence of death from possible (blue), probable (red) and proven (green) invasive fungal disease (IFD) in children treated for acute lymphoblastic leukemia.
The X-axis represents the time period of one year after diagnosis of IFD.
See this image and copyright information in PMC

References

    1. Smith MA, Altekruse SF, Adamson PC, Reaman GH, Seibel NL. Declining childhood and adolescent cancer mortality. Cancer. 2014;120:2497–506. doi: 10.1002/cncr.28748. - DOI - PMC - PubMed
    1. Hough R, Vora A. Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment) Hematol Am Soc Hematol Educ Program. 2017;2017:251–8. doi: 10.1182/asheducation-2017.1.251. - DOI - PMC - PubMed
    1. Essig S, Li Q, Chen Y, Hitzler J, Leisenring W, Greenberg M, et al. Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2014;15:841–51. doi: 10.1016/S1470-2045(14)70265-7. - DOI - PMC - PubMed
    1. Lund B, Asberg A, Heyman M, Kanerva J, Harila-Saari A, Hasle H, et al. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2011;56:551–9. doi: 10.1002/pbc.22719. - DOI - PubMed
    1. O’Connor D, Bate J, Wade R, Clack R, Dhir S, Hough R, et al. Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003. Blood. 2014;124:1056–61. doi: 10.1182/blood-2014-03-560847. - DOI - PubMed

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