title: Antifungal treatment by amphotericin B and 5-fluorocytosine delays the recovery of normal hematopoietic cells after intensive cytostatic therapy for acute myeloid leukemia.
abstract: Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B (ampho B) alone or in combination with 5-Fluorocytosine (5-FC). Because of the potential myelosuppressive side effects of 5-FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5-FC treatment for proven or suspected systemic fungal infections. The study population comprised 87 patients who were treated by standard chemotherapy for acute myeloid leukemia (AML) at first diagnosis or relapse. Twenty-two patients underwent systemic antifungal therapy consisting of ampho B (3 to 10 mg/kg/d) and 5-FC (150 mg/kg/d) for 3 to 33 days (median, 12 days). The remaining 65 patients served as controls to assess the hematologic recovery time (TR) as defined by the interval between the onset of chemotherapy and the post-treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm. In patients receiving antifungal therapy, a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days (P = 0.0016) for the control group. No correlation was found between TR and the total dose of either ampho B or 5-FC or the type of antileukemic regimen. A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5-FC treatment was started in patients with proven or only suspected fungal infections, causing a similar delay of TR in both groups. The present data strongly suggest a myelosuppressive effect of ampho B/5-FC antifungal treatment in patients after intensive chemotherapy for acute leukemias.
authors.affiliation: Department of Internal Medicine, University of Münster, Federal Republic of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: M E
authors.initials: ME
authors.lastname: Essink
authors.forename: W
authors.initials: W
authors.lastname: Fegeler
authors.forename: M
authors.initials: M
authors.lastname: Zühlsdorf
authors.forename: C
authors.initials: C
authors.lastname: Sauerland
authors.forename: T
authors.initials: T
authors.lastname: Büchner
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy* / Q000209:etiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005437:Flucytosine / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged; D011897:Random Allocation
chemical_list: D000970:Antineoplastic Agents; D000666:Amphotericin B; D005437:Flucytosine