Table 1.
Antineoplastic agent-induced CLS using the World Health Organization VigiBase
| Substances | Molecules | Total no. of AEs | No. of CLS cases | Serious CLS, n (%) | Fatal CLS, n (%) |
|---|---|---|---|---|---|
| Antimetabolites | |||||
| Purine analogues | Clofarabine | 2086 | 52 | 51 (98) | 33 (63) |
| Fludarabine | 9772 | 10 | 9 (90) | 5 (50) | |
| Pyrimidine analogues | Gemcitabine | 40,688 | 83 | 72 (87) | 14 (17) |
| Cytarabine | 23,466 | 33 | 31 (94) | 12 (36) | |
| Folic acid analogues | Pemetrexed | 14,597 | 4 | 4 (100) | 1 (25) |
| Immunostimulants | |||||
| IL | IL-2 (Aldesleukin) | 1531 | 19 | 16 (84) | 6 (32) |
| IL-11 (Oprelvekin) | 509 | 11 | 6 (55) | 3 (27) | |
| Colony-stimulating factors | Pegfilgrastim | 20,409 | 20 | 20 (100) | 4 (20) |
| Filgrastim | 10,306 | 14 | 12 (86) | 5 (36) | |
| GM-CSF | 1920 | 6 | 3 (50) | 0 (0) | |
| G-CSF | 1222 | 4 | 4 (100) | 2 (50) | |
| Lenograstim | 1556 | 3 | 3 (100) | 0 (0) | |
| Plant alkaloids and other natural products | |||||
| Taxanes | Docetaxel | 69,525 | 46 | 40 (87) | 5 (11) |
| Paclitaxel | 71,543 | 12 | 9 (75) | 3 (25) | |
| Vinca alkaloids and analogues | Vincristine | 28,746 | 8 | 8 (100) | 3 (38) |
| Podophyllotoxin derivatives | Etoposide | 28,402 | 17 | 17 (100) | 10 (59) |
| Alkylating agents | |||||
| Nitrogen mustard analogues | Cyclophosphamide | 74,270 | 34 | 34 (100) | 14 (41) |
| Melphalan | 7559 | 6 | 5 (83) | 4 (67) | |
| Bendamustine | 7586 | 4 | 4 (100) | 2 (50) | |
| Alkyl sulfonates | Busulfan | 3880 | 6 | 6 (100) | 1 (17) |
| Treosulfan | 376 | 5 | 5 (100) | 3 (60) | |
| Ethylene imines | Thiotepa | 1688 | 5 | 5 (100) | 3 (60) |
| Cytotoxic antibiotics (anthracyclines) and related substances | Daunorubicin | 6122 | 10 | 10 (100) | 4 (40) |
| Doxorubicin | 60,792 | 8 | 8 (100) | 3 (38) | |
| Other antineoplastic agents | |||||
| Platinum compounds | Oxaliplatin | 57,505 | 10 | 10 (100) | 1 (10) |
| Carboplatin | 48,738 | 7 | 7 (100) | 2 (29) | |
| Monoclonal antibodies | Rituximab | 54,743 | 19 | 19 (100) | 5 (26) |
| Alemtuzumab | 8119 | 6 | 6 (100) | 3 (50) | |
| Trastuzumab | 23,502 | 11 | 11 (100) | 1 (9) | |
| Dinutuximab | 46 | 4 | 4 (100) | 0 (0) | |
| Bevacizumab | 51,962 | 11 | 11 (100) | 1 (9) | |
| Blinatumomab | 1671 | 3 | 3 (100) | 1 (33) | |
| Nivolumab | 17,578 | 4 | 4 (100) | 2 (50) | |
| Other agents | Denileukin diftitox | 348 | 48 | 36 (75) | 12 (25) |
| Bortezomib | 25,441 | 13 | 13 (100) | 4 (31) | |
| Pentostatin | 657 | 6 | 6 (100) | 1 (17) | |
| Bexarotene | 566 | 5 | 5 (100) | 0 (0) | |
| Pegaspargase | 3756 | 5 | 5 (100) | 2 (40) | |
AE, adverse event; CLS, capillary leak syndrome; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–macrophage CSF; IL, interleukin.
Adapted with permission from Pineton de Chambrun M, Gousseff M, Mauhin W, et al, EurêClark Study Group. Intravenous immunoglobulins improve survival in monoclonal gammopathy-associated systemic capillary-leak syndrome. Am J Med. 2017;130:1219.e19–1219.e27.