First Line Antifungal Treatment with Caspofungin of Oncohemopatic Patients. A Single Centre Experience.
Authors: Bonini Alessandro , Tieghi Alessia , Gugliotta Luigi 
Published: October 2019

Abstract
Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia and among them fungal infections are the most difficult to treat and a major cause of mortality. The availability of a new class of antifungal drugs (echinocandins) could improve the chance of cure. Caspofungin (Caspo) is the first drug which is able to destroy the fungal cell wall. Since January 2004 we have treated 28 consecutive adult oncohemopatic and neutropenic pts with Caspo as first line therapy. In case of persistent fever (4 days) despite broad spectrum antibiotic therapy (association of Tazobactam/Piperacillin, Amikacin with or without Vancomycin) with negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test (this test is available at our Centre since February 2006) were performed. In the presence of any other sign or symptom we performed any other test according to the physicyan’s choice. In case of possible, probable or proven fungal infection (according to the EORTC criteria) Caspo was administered at the dosage of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. The pts were 15 males and 13 females; the mean age was 46 yrs (range 18–66 yrs). The diagnoses were: acute myeloid leukemia 13, acute lymphoblastic leukemia 5, multiple myeloma 2, lymphoma 8; the disease’s phases were: onset 9, complete remission 11, relapse 2, resistant 6. Six pts received an allogeneic and 4 an autologous BMT; the other pts received an induction or consolidation or rescue chemotherapy course. All the pts had severe neutropenia and the fungal infections were proven in 3 cases (2 aspergillus spp and 1 aspergillus fumigatus), probable in 3 cases and possible in 22 cases. The first site of infection was the lung in 27 pts and paranasal sinuses in 1 patient. CT scan was positive (halo sign, air-crescent sign or cavitation) in all the pts with a lung localization. The mean time of treatment was 18 days (range 6–21 days). The treatment was not discontinued for anyone because of adverse events and no modifications of the dosage were necessary. All the pts submitted to an allogeneic BMT received concomitant therapy with Cyclosporine A and we had not to change the dosage and we did not found any renal or liver alterations. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion as premedication. No breakthrough fungal infections were found. The infection was cured in 24/28 pts; 4 pts died for fungal infection progression (3 with a progression to the brain and in 1 case the infection remained in the lungs). For all the cured pts there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial fact for the resolution of the infection. Among the 24 cured patients 8 died later: 5 for hematologic disease and 3 for sepsis during malignant disease recurrence. In 2 cases there was the recurrence of the fungal infection despite the secondary prophylaxis with Caspo. In conclusion we can say we have a new treatment option for fungal infections in neutropenic pts with a new mechanism of action; this option seems safe, it does not preclude any other treatment (such as Cyclosporine), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost is lower than other antifungal treatments.