An approach to intensive antileukemia therapy in patients with previous invasive aspergillosis

PURPOSE: In an attempt to decrease the risk for reactivation of life-threatening invasive aspergillosis (IA) during subsequent myelosuppression in patients with previously diagnosed IA who were receiving antileukemic treatment, we evaluated the role of intensive antifungal therapy with amphotericin B and 5-fluorocytosine administered prophylactically throughout the antileukemic regimen and induced granulocytopenia to prevent IA reactivation without compromising the intensive chemotherapy. PATIENTS and METHODS: During a 30-month period, 10 patients with acute myelogenous leukemia and primary IA developing during initial antileukemia induction therapy and severe granulocytopenia (less than 100/mm3) underwent 14 subsequent courses of intensive marrow aplasia-producing chemotherapy during early complete remission or at leukemia relapse. All patients had evidence of ongoing IA healing by lung computerized tomography (CT) prior to reinstitution of intensive chemotherapy. Nine patients receiving 13 chemotherapy courses also received aggressive prophylactic anti-IA therapy with amphotericin B (1.0 mg/kg/day) and 5-fluorocytosine beginning at least 48 hours prior to antileukemia therapy institution and continued until the time of granulocyte recovery. RESULTS: All nine patients receiving aggressive antifungal therapy survived without clinical evidence of IA reactivation. Transient radiographic evidence of IA reactivation during granulocytopenia was detected by lung CT during two of the 13 chemotherapy courses. In contrast, the patient who did not receive anti-IA prophylaxis had both clinical and radiographic evidence of IA reactivation during severe granulocytopenia and died. Anti-IA prophylaxis was achieved without irreversible nephrotoxicity, prolonged marrow suppression, alteration of antileukemia treatment, or negative impact on clinical outcome relative to acute leukemia. CONCLUSION: This approach of antifungal prophylaxis in adults with acute leukemia and documented primary IA occurring during initial induction chemotherapy has been successful in preventing clinically significant IA reactivation during subsequent granulocytopenic courses, and allows for administration of additional intensive antileukemia therapy.