Amphotericin B colloid dispersion (ABCD) for the treatment of proven or presumed fungal infections in immunocompromised patients with hematologic malignancies

B. Sirohi*, R. Powles, J. Treleaven, S. Singhai, S. Kulkarni, R. Saso, C. R. Pinkerton, S. Meiler, S. Vaidya, K. Murphy, A. Conway, C. Seybel, D. Cunningham, J. Mehta

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

ABCD consists of amphotericin and sodium cholesteryl sulfate in a 1:1 molar ratio. Belween 7/99 and 7/00, 58 immunocompromised/neutropenic patients (2-71 y, médian 48) with hématologie malignancies (31 acute leukemia, 16 myeloma, 4 lymphoma, 7 other) received 65 courses of ABCD at daily dose of 1 mg/kg for presumed (n=55) and 3-4 mg/ kg for proven/strongly suspected (n=9; 3 microbiologie, 6 radiologie) fungal infections. ABCD administration followed allogeneic (n=14), autologous (n=17), or syngeneic (n=2) stem cell transplantation, or chemotherapy (n=32). The major indications for the use of ABCD were renal dysfunction or potassium requirements >3 mmol/kg/d on conventional amphotericin. In view of known problems with infusion-related toxicity of ABCD, each dose was administered over 4-6 h after premedication comprising l g paracetamol, 10 mg chlorpheniramine, 25-50 mg pethidine, 100 mg hydrocortisone and 20 mg nefopam in various combinations. Courses comprising >4 doses were évaluable for efficacy, and all courses were évaluable for toxicity. The median neutrophil count at initiation of treatment was 0. 46 courses in 43 patients (4-26 doses, median 9) were évaluable for efficacy. 9 courses in proven infections resulted in 2 complete and 4 partial responses, and 3 failures (67% response). 37 courses in presumed infections resulted in 23 complete and 4 partial responses, and 10 failures (73% response). The overall response rate was 72%. The change in serum creatinine from the beginning to the end of therapy was -145 to +331 Hmol/L (median -27). Despite extensive premedication, significant infusion-related toxicity was seen: 30 (46%) rigors, 26 (40%) pyrexia, 6 (9%) bronchospasm, 6 (9%) rash, and 4 (6%) anaphylaxis. At least 1 of these toxicities was seen in 37 (57%). The intensity of infusion-related reactions decreased with subsequent doses. 12(18%) patients experienced hepatotoxicity which could not be definitely attributed to ABCD. The underlying intervention (type of transplant or chemotherapy) did not affect efficacy or toxicity. We conclude that despite its efficacy, the high incidence of infusion-related side effects seen in ABCD-treated patients despite extensive premedication is likely to be a limiting factor in the usefulness of this drug. The frequent use of corticosteroids mandated by ABCD may be detrimental in patients who are already immunocompromised and/or neutropenic.

Original languageEnglish (US)
Pages (from-to)37b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sirohi, B., Powles, R., Treleaven, J., Singhai, S., Kulkarni, S., Saso, R., Pinkerton, C. R., Meiler, S., Vaidya, S., Murphy, K., Conway, A., Seybel, C., Cunningham, D., & Mehta, J. (2000). Amphotericin B colloid dispersion (ABCD) for the treatment of proven or presumed fungal infections in immunocompromised patients with hematologic malignancies. Blood, 96(11 PART II), 37b.