Invasive Fungal Infection in Acute Leukemia Patients: What Is Their Impact on the Chemotherapy Schedule?.
Authors: Even Caroline , Pautas Cecile , Hicheri Yosr , Maury Sebastien , Kuentz Mathieu , Botterel Francoise , Bretagne Stephane , Bastuji-Garin Sylvie , Cordonnier Catherine 
Published: October 2019

Abstract
Invasive fungal infection (IFI) occurs in 2–12% of acute leukemia patients, with different prevalences according to centers, and phases of treatment. The mortality rates of the main IFI (i.e., aspergillosis and candidiasis) are well illustrated in the literature, as well as the risk of fungal relapse during subsequent periods at risk, such as a new neutropenic phase, or transplant. However, few data are available about the impact of IFI on the subsequent chemotherapy schedule. Clinicians are usually reluctant to give the full chemotherapy doses on time, due to the risk of life-threatening fungal relapse during the subsequent courses. Even with secondary prophylaxis which is now widely given, they usually delay or decrease the doses of chemotherapy. This may impact on the leukemia outcome.
Objective: The aim of this single-institution retrospective study was to look at the impact of proven or probable IFI onset on the application of the chemotherapy schedule as planned in the initial strategy in patients with acute leukemia. Delays, and changes in chemotherapy doses and drug choices were evaluated and compared to the planned schedule in the protocole.
Methods: All consecutive acute leukemia patients with a first episode of proven or probable IFI according to the EORTC-MSG criteria between 2000–2006 were reviewed. All patients have been treated in, or according to, clinical research protocols where timing and doses of chemotherapy were predefined. Patients who were planned for allogeneic transplant were excluded as those who were at their last consolidation course when they got IFI. Any delay, dose decrease or dose change were defined as any difference compared to the planned schedule.
Results: 28 patients (7 candidiasis, 20 aspergillosis, 1 zygomycosis) were included (M/F: 15/13; mean age: 54y), including 27 acute myeloid leukemia and one acute lymphoblastic leukemia. Eleven (39%) were proven, 17 (61%) were probable. Twenty (71%) of these IFI occurred during the first induction phase. All patients were treated for their IFI with ≥ 1 antifungal, and 4 of them had a surgical resection of the main fungal lesion (s). Seventeen of 28 (60%) had their next course delayed (median delay: 14 days) when compared to the planned protocole. The doses of the antineoplastic drug(s) were modified in 7 (25%) patients. Only 9 (32%) patients got their next chemotherapy course without any modification in time, dose, or choice of drug. Although the number of patients in our study does not allow definite conclusions, these changes should have an impact on leukemia-free and overall survivals.
Conclusion: Due to the risk of fungal relapse during a subsequent period at risk, IFI has a practical impact on the dates, doses, and choices of chemotherapy in acute leukemia in more than two thirds of the patients, due to subjective decisions of the clinicians. Effective antifungal strategies are needed to avoid the onset of IFI in acute leukemia patients.