Table 5.
Studies of conventional pharmacological second-line treatments for steroid-refractory aGvHD that included children.
| Investigational agent | Study design | Patients, N/years | Overall response rate | Complete response rate | Overall survival rate | Main toxicities | References |
|---|---|---|---|---|---|---|---|
| Ruxolitinib | Phase III | 154/12–73 | 62% | 40% (durable response on day 56) | 53% at 1 year | Thrombocytopenia: 33% Anaemia: 30% CMV infection/reactivation: 39% |
Zeiser et al. (107) |
| Mofetil mycophenolate | Phase II | 26 (13with aGvHD)/17-53 | 31% | 15% | 33% at 2 years | For the whole population: Gastrointestinal: 27% Infection: 31% CMV: 11% |
Kim et al. (108) |
| Phase II | 19/4–54 | 47% | 31% | 16% at 1 year | Neutropenia:10.5% Abdominal pain: 5% Pulmonary infiltrates: 5% Neutropenia+gastrointestinal toxicity: 15,8% Infection as cause of death: 32% |
Furlong et al. (109) | |
| Retrospective | 14/0–17 | 79% | 50% | 85%, median follow-up 35 months | CMV reactivation: 29% CMV retinitis: 7% ADV infection: 7% Haemorrhagic cystitis: 14% Aspergillosis: 7% Neutropenia: 7% Thrombocytopenia: 7% |
Inagaki et al. (110) | |
| Anti-TNF antibody infliximab | Retrospective | 24 (22 assessable for response)/0–18 | 82% | 54% | 46% at 1 year; 21% at 2 years | Bacterial infection: 77% Viral infection: 32% Fungal infection: 13.6% |
Sleight et al. (111) |
| Retrospective | 32/2–66 | 59% | 19% | 41% | Infections in 72% Septicaemia and septic shock: 22% Pneumonia: 28% Enteritis: 12.5% Encephalitis: 3% CMV reactivation: 41% Invasive fungal infection: 6% |
Patriarca et al. (112) | |
| ATG | Retrospective | 79/NA | 54% | 20% | 32% at 1 year | Bacterial infection: 37% Fungal infection: 18% CMV: 10% |
MacMillan et al. (113) |
| Phase II/III | ABX-CBL: 48/2–65; Horse ATG: 47/2–65 | ABX-CBL:56%; ATG:57% | ABX-CBL:29%; ATG:32% | ABX-CBL:35% at 18 months; ATG: 45% at 18 months | Infections: 98% (ABX-CBL), 100% (ATG) Fever: ABX-CBL 20%, ATG 30% Hypertension: ABX-CBL 30%, ATG 28% Hyperglycaemia: ABX-CBL 24%, ATG 26% Abdominal pain: ABX-CBL 15%, ATG 33% |
MacMillan et al. (114) | |
| Alemtuzumab | Retrospective | 18/1–59 | 83% | 33% | 55% at 11 months | Infection: 78% CMV reactivation: 67% Grade 3 neutropenia: 33% Grade 3 thrombocytopenia: 22% Chills, fever and headache: 28% Tuberculosis: 1 patient |
Gomez-Almaguer et al. (115) |
| Phase II | 18/13–68 | 99% | 28% | 33% at 36.5 weeks | Sepsis: 28% Pneumonia: 39% Viral infection: 44% Fungal infection: 22% CMV: 56% EBV: 11% |
Schub et al. (116) | |
| Phase I/II | 15/1.4–27 | 67% | 40% | 80% at 6 months | Fever: 26% Thrombocytopenia: 53% Viremia: 100% CMV disease: 2 patients EBV PTLD: 1 patient |
Khandewall et al. (117) | |
| Anti IL-2 receptor antibody daclizumab | Retrospective | 13/paediatric | 92% | 46% | 46% at 14 months | CMV reactivation: 54% VVZ reactivation: 15% Sepsis: 8% EBV reactivation15% |
Miano et al. (118) |
| Phase II | 62/1–53 | 90% | 68,8% | 54.6% at 4 years | CMV reactivation: 39% Infections as cause of death: 11% |
Bordigoni et al. (119) | |
| Retrospective | 57/0–57 | 54% | 76% for patients ≤ 18 years old | Median survival: 3.6 months | Opportunistic infection: 95% Bacterial infection: 88% Fungal infection: 51% Viral infection: 53% CMV: 35% EBV: 7% |
Perales et al. (120) | |
| Anti IL-2 receptor antibody basiliximab | Retrospective | 34/2–38 | 82% | 32% | 20% at 5 years | NA | Funke et al. (121) |
| Retrospective | 230 (74 <18 years) | 78.7 | 60.9 | 61.7% at 4 years | Bacterial infection: 52.6% Fungal infection: 16.1% Viral infection: 3.8% |
Liu et al. (122) | |
| Retrospective (haploidentical HSCT) | 100/1–17 | 85% | 74% | 76,2% at 3 years | Bacterial infection: 11% Fungal infection: 7% CMV viremia: 53% EBV viremia: 11% HHV-6 viremia: 7% |
Tang et al. (123) | |
| Basiliximab + etanercept | Prospective | 65/9–55 | 90.8% | 75.4% | 54.7% at 2 years | Cytopenia: 49.2% Haemorrhagic cystitis: 28% Fungal infection: 36% CMV reactivation: 57% EBV reactivation: 6.2% |
Tan et al. (124) |
| Pentostatin | Phase I | 23(22 assessable for response)/0–63 | 77% | 64% | 26%, median survival 85 days |
Lymphopenia: 100% Thrombocytopenia: 4% Infection: 9% |
Bolaños-Meade et al. (125) |
aGvHD, acute graft versus host disease; ATG, anti-thymocyte globulin; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSCT, haematopoietic stem cell transplantation; HHV-6, human herpesvirus 6; IL, interleukin; PTLD, post-transplant lymphoproliferative disorder; TNF, tumour necrosis factor.