Table 4.
Review of prospective studies of primary antifungal prophylaxis with L-AmB in hematological and stem cell transplant populationsa
| Type of study (reference) | Population (no. of patients) | Schedule of L-AmB administration | Main toxicity and tolerability result(s) | Main efficacy result(s) |
|---|---|---|---|---|
| Prospective, double blind, multicenter, placebo controlled (18) | Adult neutropenic patients receiving allogeneic SCT (36 in the L-AmB arm and 40 in the placebo arm) | 1 mg/kg/day | 3 allergic reactions | Proven/probable IFDs, 2.8% in the L-AmB arm vs 7.5% in the placebo arm |
| Prospective, double blind, multicenter, placebo controlled (19) | Adult patients receiving chemotherapy or SCT for HM (74 in the L-AmB arm and 87 in the placebo arm) | 2 mg/kg 3 times weekly during neutropenia | Treatment-related toxicity was modest, and no additional toxicity was observed in patients receiving L-AmB | Proven/probable IFDs, 0% in the L-AmB arm vs 2.3% in the placebo arm; 1 death attributed to IFD for each arm |
| Prospective, randomized, single center, open label, placebo controlled (20) | Pediatric patients receiving chemotherapy or autologous SCT for HM or solid tumor (16 in the L-AmB arm and 13 in the placebo arm) | 1 mg/kg 3 times weekly during neutropenia | No difference in renal toxicity and hypokalemia; L-AmB was discontinued in 19% of cases due to infusion-related reactions | Proven/probable IFDs, 31.2% in the L-AmB arm vs 46.1% in the control arm; no death attributed to IFD |
| Prospective, randomized, single center, open label (21) | Adult AML patients undergoing induction chemotherapy (62 in the L-AmB arm and 67 in the control arm) | 3 mg/kg 3 times weekly during neutropenia | The L-AmB-treated patients more often developed increased bilirubin levels, increased creatinine levels, and infusion-related symptoms | Proven/probable IFDs, 4.8% in the L-AmB arm vs 4.5% in the control arm |
| Prospective, randomized, single center, open label (22) | Adult patients receiving allogeneic SCT for HM (75 in the L-AmB arm and 57 in the control arm) | 50 mg every other day during neutropenia | No CTC grade 3 or 4 toxicities were observed | Proven/probable IFDs, 6.7% in the L-AmB arm vs 35% in the control arm (P = 0.001); death attributed to IFD, 2.7% in the L-AmB arm vs 12.3% in the control arm (P = 0.07) |
| Single center, prospective, uncontrolled (23) | Pediatric and adolescent patients receiving allogeneic SCT for HM (51) | 3 mg/kg daily until day 100 from SCT | Grade 3–4 side effects, hypokalemia in 4% of patients, nephrotoxicity in 12%; L-AmB was discontinued in 11% of patients due to toxicity | Proven/probable IFDs, 10%; no death attributed to IFD |
| Prospective, single center, historically controlled (24) | Pediatric patients receiving chemotherapy or autologous SCT for HM (187 prophylaxis courses in 44 patients) | 2.5 mg/kg twice weekly during neutropenia | L-AmB was discontinued in 9% of patients due to allergic reactions; only 1 grade 3 reaction; grade 3–4 hypokalemia in 15.2% of prophylaxis courses | No breakthrough proven-probable IFD while on prophylaxis |
| Single center, prospective, pharmacokinetic (25) | Pediatric patients receiving allogeneic SCT (14) | 10 mg/kg weekly for 4 wk | No significant change in serum creatinine level; none of the patients developed hypokalemia, hypomagnesemia, or increased alkaline phosphatase or transaminase levels; only 1 infusion toxicity requiring withholding of the wk 4 dose | Only 1 patient developed evidence of IFD |
| Single center, prospective, uncontrolled (26) | Adult neutropenic patients receiving allogeneic SCT and with GVHD (21) | 7.5 mg/kg once weekly during treatment of GVHD | L-AmB was discontinued in 33% of patients, 19% due to nephrotoxicity and 9.5% due to infusion-related adverse events | Only one IFD; no death attributed to IFD |
| Multicenter, prospective, pilot, phase II (27) | Adult patients receiving chemotherapy for AL or allogeneic SCT (29) | 10 mg/kg weekly for 4 wk in AL patients and for 8 wk in SCT patients | Grade 3–4 AEs, 2/21 AL patients and 6/8 SCT patients; enrollment of SCT patients was stopped | Proven/probable IFDs, 4/29 (13.8%); 1 death attributed to IFD |
| Single center, prospective, pharmacokinetic (28) | Adult patients receiving allogeneic or autologous SCT (21) | 1 mg/kg/day for 15 days (7 patients), 7.5 mg/kg/wk for 2 wk (7 patients), single 15-mg/kg dose (7 patients) | For the daily dosing (1-mg/kg) group, 1 patient withdrew on day 1 due to sternal pain, and 1 patient developed CTC grade 3 hypokalemia; for the weekly dosing (7.5-mg/kg) group, 1 patient was withdrawn due bronchospam after the first dose, and 1 patient developed CTC grade 3 hypokalemia; for the single-dose (15-mg/kg) group, 2 patients developed CTC grade 3 and 1 patient developed CTC grade 4 hypokalemia | Not reported |
a
HM, hematologic malignancies; AL, acute leukemia; GVHD, graft-versus-host disease.