Table 1.
Characteristic of included studies
| References | Study design, country | Patient population | Allo-HSCT percentage | Interventions and sample sizes (n) | Outcomes | ||
|---|---|---|---|---|---|---|---|
| A | B | C | |||||
| Boogaerts 2001 [17] | Open, multicenter, randomized, controlled clinical trial, multi-countries (North America, Europe and Oceania) | Age ≥ 18, hematologic cancer with intensive myelosuppressive cytotoxic therapy or auto-HSCT support. | 0 | Itraconazole 200 mg iv. q12h for the first 48 h, followed by 200 mg iv. qd from days 3 to 14. From day 15, 400 mg/d po (n = 179). | C-AmB 0.7–1.0 mg/kg iv. qd (n = 181) | / | ①②③ |
| Caselli 2012 [18] | Multicentre, randomized, controlled trial, Italy | Age ≤ 18, with at least one of the following features: AML, early relapse of ALL, ongoing auto-HSCT with bone marrow as the source of the stem cells, a neutropenic score ≥5. | 0 | L-AmB 3 mg/kg iv. qd (n = 25) | Caspofungin at a LD of 70 mg/m2 iv. on day 1, then 50 mg/m2 iv. qd (n = 31) | / | ③ |
| Age ≤ 18, without other features mentioned above. | 0 | L-AmB 3 mg/kg iv. qd (n = 15) | Caspofungin at a LD of 70 mg/m2 iv. on day 1, then 50 mg/m2 iv. qd (n = 17) | NAT(n = 16) | |||
| Groll 2010 [19] | Open, prospective, randomized multicenter phase II trial, Germany | Age ≥ 18, with allo-HSCT and immunosuppression with cyclosporine. | 100% | Caspofungin at a LD of 70 mg iv. on day 1, then 50 mg iv. qd (n = 18) | L-AmB 3 mg/kg iv. qd (n = 20) | / | ①②③ |
| Jadhav 2012 [20] | Randomized, multicenter trial, India | Age > 2 and < 60, with chemotherapy or BMT. | NR | L-AmB 3 mg/kg iv. qd (n = 23) | C-AmB 1 mg/kg iv. qd (n = 20) | L-AmB 1 mg/kg iv. qd (n = 22) | ①②③ |
| Jeong 2016 [33] | Randomized, controlled, prospective, multicenter study, Korea | Age ≥ 18, with intensive anticancer chemotherapy for acute leukemia, highly aggressive lymphoma, or other hematological malignancies. | 0 | Micafungin 100 mg iv. qd (n = 73) | Itraconazole200 mg iv. bid on Day 1 and 2, then 200 mg iv. qd (n = 75) | / | ①③ |
| Maertens 2010 [21] | Prospective, randomized, double-blind study, multi-countries (North America and Europe) | Age > 2 and < 17, with allo-HSCT or chemotherapy for a relapse of AML or ALL. | 40.9% | Caspofungin 70 mg/m2 LD iv. on Day 1, then 50 mg/m2 iv. qd (maximum 70 mg/d) plus placebo corresponding to L-AmB (n = 15) | L-AmB 3 mg/kg iv. qd plus placebo corresponding to caspofungin (n = 7) | / | ①③ |
| Age > 2 and < 17, without allo-HSCT or chemotherapy for a relapse of AML or ALL. | 0 | Casfofungin 70 mg/m2 LD iv. on Day 1, then 50 mg/m2 qd (maximum 70 mg/d) plus placebo corresponding to L-AmB (n = 41) | L-AmB 3 mg/kg iv. qd plus placebo corresponding to Caspofungin (n = 18) | / | |||
| Meunier 1989 [22] | Multicenter Randomized trial, multi-countries (Europe) | Age > 15. | NR | AmB 1.2 mg/kg iv. qod or 0.6 mg/kg iv. qd (n = 57) | NAT (n = 51) | / | ①②③ |
| Age ≤ 15. | NR | AmB 1.2 mg/kg iv. qod or 0.6 mg/kg iv. qd (n = 11) | NAT (n = 13) | / | |||
| Oyake 2015 [23] | open-label, randomized, multicenter, comparative trial, Japan | Age ≥ 16. | 2.0% | Micafungin 150 mg iv. qd (n = 49) | Voriconazole at a LD of 6 mg/kg iv. bid on day 1 followed by 4 mg/kg iv. bid (n = 45) | / | ①②③ |
| Prentice 1997 [24] | Prospective, open-label, randomized, multicenter trial, multi-countries (Europe) | Adult patients. | NR | AmB 1 mg/kg iv. qd (n = 39) | L-AmB 3 mg/kg iv. qd (n = 47) | L-AmB 1 mg/kg iv. qd (n = 47) | ③ |
| Pediatric patients. | NR | AmB 1 mg/kg iv. qd (n = 61) | L-AmB 3 mg/kg iv. qd (n = 71) | L-AmB 1 mg/kg iv. qd (n = 70) | |||
| Schiel 2006 [25] | Randomized, controlled multi-center trial, Germany | Age ≥ 18, with high grade hematological disorders. | 0 | NAT (n = 54) | Fluconazole 800 mg iv. at day 1, followed by 400 mg iv qd (n = 56) | / | ①③ |
| Schuler 2007 [26] | Open, randomized, multicenter, parallel-group trial, Germany | Age ≥ 18, with haematological malignancy and allo-HSCT. | 100% | Itraconazole at a LD of 200 mg iv. q12h for 2 days, 200 mg iv. qd for 12 days, then solution 200 mg po. q12h (n = 26) | AmB 0.7–1 mg/kg iv. qd(n = 24) | / | ①②③ |
| Age ≥ 18, with haematological malignancy and without allo-HSCT. | 0 | Itraconazole at a LD of 200 mg iv. q12h for 2 days, 200 mg iv. qd for 12 days, then solution 200 mg po. q12h (n = 55) | AmB 0.7–1 mg/kg iv. qd(n = 57) | / | |||
| Viscoli 1996 [27] | Prospective, randomised, multicentre, open-label study, Italy | With cancer (including autologous or allogeneic BMT for a neoplastic disease). | 41.1% | Fluconazole 6 mg/kg iv. qd (maximum 400 mg/day) (n = 56) | AmB 0.8 mg/kg iv. qd (n = 56) | / | ①②③ |
| Walsh 1999 [28] | Randomized, double-blind, multicenter trial, United states | Age > 2 and < 80, with chemotherapy for leukemia, lymphoma, or other cancers, or with BMT or peripheral HSCT. | NR | L-AmB 3 mg/kg iv. qd (n = 343) | AmB 0.6 mg/kg iv. qd (n = 344) | / | ①②③ |
| Walsh 2002 [29] | Open-label, prospective, randomized, multicenter, international comparative trial, multi-countries (Europe and North America) | Age ≥ 12, with allo-HSCT or chemotherapy for relapsed leukemia. | 54.6% | Voriconazole at a LD of 6 mg/kg iv. q12h on day 1 followed by 3 mg/kg iv. q12h or 200 mg po. q12h after at least 3 days of intravenous therapy (n = 143) | L-AmB 3 mg/kg iv. qd (n = 141) | / | ①②③ |
| Age ≥ 12, without allo-HSCT or chemotherapy for relapsed leukemia. | 0 | Voriconazole at a LD of 6 mg/kg iv. q12h on day 1 followed by 3 mg/kg iv. q12h or 200 mg po. q12h after at least 3 days of intravenous therapy (n = 272) | L-AmB 3 mg/kg iv. qd (n = 281) | / | |||
| Walsh 2004 [30] | Prospective, double-blind study, multi-countries (North America, South America, Europe, Asia and Oceania) | Age ≥ 16, with allo-HSCT or chemotherapy for relapsed leukemia. | 28.0% | Caspofungin 70 mg iv. LD on Day 1, then 50 mg iv. qd plus placebo corresponding to L-AmB | L-AmB 3 mg/kg iv. qd plus placebo corresponding to caspofungin | / | ①③ |
| Age ≥ 16, without allo-HSCT or chemotherapy for relapsed leukemia. | 0 | Caspofungin 70 mg iv. LD on Day 1, then 50 mg qd plus placebo corresponding to L-AmB | L-AmB 3 mg/kg iv. qd plus placebo corresponding to caspofungin | / | |||
| Wang 2007 [31] | Open, randomized, controlled trial, China | With immunosuppression, long term use of glucocorticoid or neutropenia after radiotherapy and chemotherapy. | 41.7% | Caspofungin at a LD of 70 mg iv. on day 1, then 50 mg iv. qd (n = 32) | L-AmB 3 mg/kg iv. qd (n = 28) | / | ①③ |
| Wingard 2000 [32] | Randomized, double-blind comparative Trial, United States | Age > 2. | 15.3% | L-AmB 3 mg/kg iv. qd (n = 85) | ABLC 5 mg/kg iv. qd (n = 78) | / | ①②③ |
①All-cause mortality; ②Fungal infection-related mortality; ③Treatment response
ABLC Amphotericin B lipid complex, ALL Acute lymphocytic leukemia, Allo-HSCT Allogeneic hematopoietic stem cell transplantation, AML Acute myelocytic leukemia, Auto-HSCT Autologous hematopoietic stem cell transplantation, BMT Bone marrow transplantation, AmB Conventional amphotericin B, L-AmB Liposomal amphotericin B, LD Loading dose, NAT No antifungal treatment, NR Not reported