First Line Treatment of Probable and Proven Invasive Aspergillosis with Caspofungin in Oncohemopatic Patients. A Single Centre Experience

Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia. In particular fungal infections are the most difficult to treat and represent a major cause of mortality. Caspofungin (Caspo) is the first drug which is able to inhibit the growth of the fungal cell wall. Since January 2004 we have treated 64 consecutive adult neutropenic pts with Caspo as first line therapy. In the setting of persistent fever (3 days) despite broad spectrum antibiotic therapy and negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test were performed. In the setting of probable or proven fungal infection (according to the revised EORTC criteria and Cornely CID 2007) Caspo was administered at the dose of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. They were 35 males and 29 females; the mean age was 56 yrs (range 19–77 yrs). The diagnoses were: acute leukemia 46 (72%), myeloma 2 (3%), lymphoma 14 (22%) and chronic leukemia 2 (3%); the disease’s phases were: new onset 26 (41%), remission 16 (24%), relapse 22 (35%). Thirteen pts received an allogeneic and 5 an autologous hematopoietic stem cell transplant; the other pts received an induction or consolidation or rescue chemotherapy course. Fungal infections were proven in 13 cases (20% including 11 aspergillus spp, 1 aspergillus fumigatus, 1 G. capitatum) and probable in 51 cases (80%). The first site of infection was the lung in 63 pts (98%) and paranasal sinuses in 1 patient (2%). CT scan was positive (halo sign or air-crescent sign) in all the pts with a lung localization, while the chest X-ray was positive in 40% of them. BAL was performed in 31 pts. The mean time of treatment was 18 days (range 13–25 days). Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion of Caspo were seen, and it was not necessary to administer any drug before the infusion as premedication. The global (partial and complete) response was 55/64 (86%); 9 pts died for fungal infection. The efficacy responses were generally similar for probable and proven infections. No breakthrough fungal infections were found. All surviving patients, upon discharge from the hospital, received oral treatment with Voriconazole or Posaconazole. For all the cured pts, there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial factor for the resolution of the infection. Among the 55 responsive patients, 25 (45%) died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 cases there was the recurrence of the fungal infection. In conclusion the resolution rate of the infections is very high (86%); Caspo seems safe, it does not preclude any other treatment (such as Cyclosporin A), it is well tolerated and the cost is lower than other antifungal treatments.