Principal studies reporting patients treated for endothelial syndromes
| References . | Characteristics . | Patients, n . | Median age (range), y . | Diagnostic criteria . | Onset, days from HSCT (range) . | Response rate or survival, n (%) . |
|---|---|---|---|---|---|---|
| TA-TMA | ||||||
| Rituximab | ||||||
| Au et al93 | Retrospective rituximab (375 mg/m2 per wk × 4) | 5 | 48 (1-56) | BMT-CTN | 42 (18-505) | CR 4/5 (80) |
| Jodele et al44 | Prospective biological study; rituximab (375 mg/m2 per wk for 2-10 courses) | 6 | 3.5 (2-17) | O-TMA | 32 (9-111) | CR 4/6 (67) |
| Defibrotide | ||||||
| Corti et al94 | Retrospective (40 mg/kg p.o. daily for 30-50 d) | 12 | 26 (1-55) | Hemolytic anemia, antiglobulin test (−), schystocytosis, haptoglobin ↓, LDH ↑, thrombocytopenia, CNS or renal involvement | 47 (9-100) | CR 5/12 (42)/PR 3/12 (25) |
| Yeates et al95 | Retrospective: median dose in ped: 30 mg/kg per d (range, 25-60); in ad: 400 mg/kg per d (range, 200-800) | 39 (22 ped/17 ad) | 8 (0-17)/40 (18-63) | O-TMA | 51 (10-215)/33 (15-152) | 17/22 (77)/13/17 (77) |
| Vincristine | ||||||
| Silva et al96 | Retrospective: 1-2 mg IV weekly or 0.2 mg IV daily (associated with PE and CCS) | 6 | 24.5 (13-35) | Hemolytic anemia, antiglobulin test (−), LDH ↑, thrombocytopenia, CNS or renal involvement | 49 (19-110) | CR 1/6 (17), PR 2/6 (33) |
| Mateos et al97 | Retrospective: 1 mg once daily IV on days 1, 4, and 8 ± day 11 | 7 | 18 (6-48) | Anemia, LDH ↑, thrombocytopenia, schistocytosis | 49 (25-276) | CR 6/7 (86) |
| Eculizumab | ||||||
| Jodele et al49 | Prospective: induction dose: 600 (<40 kg) or 900 mg (>40 kg); maintenance dose: 900 or 1200 every 14 d | 6 | 5 (2-10) | O-TMA | 49 (6-390) | CR 4/6 (67) |
| de Fontbrune et al48 | Retrospective: induction dose: 900 mg weekly for 4 wk, followed by maintenance (1200 mg every 14 d) | 12 (3 ped/9 ad) | 39 (1.2-66) | + | 121 (37-455) | OR 6/12 (50) |
| Jodele et al78 | Prospective: induction dose: 600 mg (<40 kg) or 900 mg (>40 kg), subsequent doses based on CH50 monitoring | 18 | 4.6 (2-15.2) | Refined TMA | 30 (18-55) | CR 11/18 (61) |
| Bohl et al98 | Retrospective: 900 mg once weekly until clinical response, followed by maintenance therapy (1200 mg every 14 d) | 24 | 48 (23-66) | O-TMA | 180 (15-984) | OR 13/15 (93) |
| IPS | ||||||
| Anti-TNF | ||||||
| Yanik et al80 | Retrospective anti-TNF+CCS (2 mg/kg per d) | 15 | 21 (1-60) | 14 (9-87) | 10/15 (66) | |
| Yanik et al81 | Prospective randomized ARM A: anti-TNF+CCS (2 mg/kg per d). ARM B: placebo + CCS (2 mg/kg per d). | A: 16; B: 18 | A: 10/16 (62); B: 12/18 (66.7) | |||
| Yanik et al92 | Prospective phase 2 anti-TNF+CCS (2 mg/kg per d) | 39 | 11 (1-17) | 20 (6-119) | 20/39 (71) | |
| Thompson et al82 | Retrospective anti-TNF+CCS (2 mg/kg per d) | 23 | 56 (35-72) | 233 (104-555) | 10/23 (43) |
| References . | Characteristics . | Patients, n . | Median age (range), y . | Diagnostic criteria . | Onset, days from HSCT (range) . | Response rate or survival, n (%) . |
|---|---|---|---|---|---|---|
| TA-TMA | ||||||
| Rituximab | ||||||
| Au et al93 | Retrospective rituximab (375 mg/m2 per wk × 4) | 5 | 48 (1-56) | BMT-CTN | 42 (18-505) | CR 4/5 (80) |
| Jodele et al44 | Prospective biological study; rituximab (375 mg/m2 per wk for 2-10 courses) | 6 | 3.5 (2-17) | O-TMA | 32 (9-111) | CR 4/6 (67) |
| Defibrotide | ||||||
| Corti et al94 | Retrospective (40 mg/kg p.o. daily for 30-50 d) | 12 | 26 (1-55) | Hemolytic anemia, antiglobulin test (−), schystocytosis, haptoglobin ↓, LDH ↑, thrombocytopenia, CNS or renal involvement | 47 (9-100) | CR 5/12 (42)/PR 3/12 (25) |
| Yeates et al95 | Retrospective: median dose in ped: 30 mg/kg per d (range, 25-60); in ad: 400 mg/kg per d (range, 200-800) | 39 (22 ped/17 ad) | 8 (0-17)/40 (18-63) | O-TMA | 51 (10-215)/33 (15-152) | 17/22 (77)/13/17 (77) |
| Vincristine | ||||||
| Silva et al96 | Retrospective: 1-2 mg IV weekly or 0.2 mg IV daily (associated with PE and CCS) | 6 | 24.5 (13-35) | Hemolytic anemia, antiglobulin test (−), LDH ↑, thrombocytopenia, CNS or renal involvement | 49 (19-110) | CR 1/6 (17), PR 2/6 (33) |
| Mateos et al97 | Retrospective: 1 mg once daily IV on days 1, 4, and 8 ± day 11 | 7 | 18 (6-48) | Anemia, LDH ↑, thrombocytopenia, schistocytosis | 49 (25-276) | CR 6/7 (86) |
| Eculizumab | ||||||
| Jodele et al49 | Prospective: induction dose: 600 (<40 kg) or 900 mg (>40 kg); maintenance dose: 900 or 1200 every 14 d | 6 | 5 (2-10) | O-TMA | 49 (6-390) | CR 4/6 (67) |
| de Fontbrune et al48 | Retrospective: induction dose: 900 mg weekly for 4 wk, followed by maintenance (1200 mg every 14 d) | 12 (3 ped/9 ad) | 39 (1.2-66) | + | 121 (37-455) | OR 6/12 (50) |
| Jodele et al78 | Prospective: induction dose: 600 mg (<40 kg) or 900 mg (>40 kg), subsequent doses based on CH50 monitoring | 18 | 4.6 (2-15.2) | Refined TMA | 30 (18-55) | CR 11/18 (61) |
| Bohl et al98 | Retrospective: 900 mg once weekly until clinical response, followed by maintenance therapy (1200 mg every 14 d) | 24 | 48 (23-66) | O-TMA | 180 (15-984) | OR 13/15 (93) |
| IPS | ||||||
| Anti-TNF | ||||||
| Yanik et al80 | Retrospective anti-TNF+CCS (2 mg/kg per d) | 15 | 21 (1-60) | 14 (9-87) | 10/15 (66) | |
| Yanik et al81 | Prospective randomized ARM A: anti-TNF+CCS (2 mg/kg per d). ARM B: placebo + CCS (2 mg/kg per d). | A: 16; B: 18 | A: 10/16 (62); B: 12/18 (66.7) | |||
| Yanik et al92 | Prospective phase 2 anti-TNF+CCS (2 mg/kg per d) | 39 | 11 (1-17) | 20 (6-119) | 20/39 (71) | |
| Thompson et al82 | Retrospective anti-TNF+CCS (2 mg/kg per d) | 23 | 56 (35-72) | 233 (104-555) | 10/23 (43) |
Note the lack of studies concerning endothelial syndromes other than TA-TMA and IPS.
ad, adults; BMT-CTN, Blood and Marrow Transplant Clinical Trials Network criteria; CCS, corticosteroid; CH50, complement inhibition 50; CR, complete response; LDH, lactate dehydrogenase; OR, overall response; O-TMA, overall TMA criteria; PE, plasma exchange; ped, pediatrics; p.o., by mouth; PR, partial response.