Secondary agents (updated from Lee et al33).
| Agent . | Published overall response rates . | Organ specific response rates (CR+PR) . | Hypothesized mechanism of action . | Side effects . | Survival . | Adult use, %* . | Pediatric use, %* . |
|---|---|---|---|---|---|---|---|
| * Percentages of adult and pediatric use from survey of 526 transplant physicians asked to choose an agent to treat steroid-refractory chronic GVHD.20 | |||||||
| Common agents | |||||||
| Mycophenolate mofetil34 –36 (Cellcept) | 46–75% response rate (N = 21–26) | Skin (53%, n = 15), mouth (67%, n = 15), liver (54%, n = 13) | Prodrug of mycophenolic acid interferes with purine synthesis in lymphocytes | Nausea, vomiting, diarrhea, abdominal cramps, neutropenia | 85% survival at 2 years | 52 | 50 |
| High-dose corticosteroids37 | 48% major response rate (N = 56) | Lympholytic at a dose of 10 mg/kg/d for 4 days | Infection, glucose intolerance, psychological effects including psychosis, insomnia | 88% survival at 1 year | 6 | 16 | |
| Extracorporeal 38,39 photopheresis | 61% response rate (N = 71) | Skin (40%, n = 48),40 sclerotic skin (67%, n = 21), mouth (77%, n = 7), eye (67%, n = 4) and lung (54%, n = 6). | Induces apoptosis in 5–10% T cells, increases regulatory T cells | Anemia, potential need for central IV access | 53% survival at 1 year | 10 | 4 |
| Sirolimus/rapamycin41,42 (Rapamune) | 63–94% clinical response (n = 16–35) | Skin (65%, n = 29), mouth (75%, n = 8), liver (33%, n = 6), eye (64%, n = 11), GI (67%, n = 6) | Binds to FKBP-12 and mTOR (mammalian target of rapamycin) to inhibit cytokine-driven T cell proliferation | Hypertriglyceridemia, renal insufficiency, cytopenias, infection | 41% survival at 2 years; 89% survival at 3 years | 7 | 4 |
| 2-deoxycoformycin43 (Pentostatin) | 53% major response rates, 2% minor response (N = 58) | Lichenoid skin (69%, n = 39), sclerotic skin, fascial, mouth (52–57%, n = 39) | Nucleoside analog that inhibits adenosine deaminase (ADA) | Nausea, vomiting, infection, renal dysfunction, rash, headache | 78% survival at 1 year | 2 | 7 |
| Tacrolimus (Prograf)44,45 | 35% response rate (N = 39) | Binds to FKBP-12 (FK binding protein) and inhibits T lymphocyte activation, concentrates in liver | Renal dysfunction, thrombotic microangiopathy, neurotoxicity, hypertension | Survival not reported | 12 | 7 | |
| Less common agents | |||||||
| Rituximab (Rituxan)46,47 | 65–70% response rate (N = 21–38) | Skin (63%, n = 28), mouth (48%, n = 21), eyes (43%, n = 14), liver (25%, n = 12), lung (38%, n = 8) | Chimeric anti-CD20 monoclonal antibody | Allergic reactions, infections, hepatitis reactivation | 76% survival at 2 years | 2 | 1 |
| Thalidomide48 –50 | 20–38% response rate (N = 23–80) | Skin (46%, n = 30), mouth (22%, n = 14); joint (78%, n = 14), lung (0%, n = 6) | Anti-inflammatory and immunosuppressive properties | Neuropathy, somnolence, constipation, neutropenia | 41% survival at 2 years | 2 | 0 |
| Agent . | Published overall response rates . | Organ specific response rates (CR+PR) . | Hypothesized mechanism of action . | Side effects . | Survival . | Adult use, %* . | Pediatric use, %* . |
|---|---|---|---|---|---|---|---|
| * Percentages of adult and pediatric use from survey of 526 transplant physicians asked to choose an agent to treat steroid-refractory chronic GVHD.20 | |||||||
| Common agents | |||||||
| Mycophenolate mofetil34 –36 (Cellcept) | 46–75% response rate (N = 21–26) | Skin (53%, n = 15), mouth (67%, n = 15), liver (54%, n = 13) | Prodrug of mycophenolic acid interferes with purine synthesis in lymphocytes | Nausea, vomiting, diarrhea, abdominal cramps, neutropenia | 85% survival at 2 years | 52 | 50 |
| High-dose corticosteroids37 | 48% major response rate (N = 56) | Lympholytic at a dose of 10 mg/kg/d for 4 days | Infection, glucose intolerance, psychological effects including psychosis, insomnia | 88% survival at 1 year | 6 | 16 | |
| Extracorporeal 38,39 photopheresis | 61% response rate (N = 71) | Skin (40%, n = 48),40 sclerotic skin (67%, n = 21), mouth (77%, n = 7), eye (67%, n = 4) and lung (54%, n = 6). | Induces apoptosis in 5–10% T cells, increases regulatory T cells | Anemia, potential need for central IV access | 53% survival at 1 year | 10 | 4 |
| Sirolimus/rapamycin41,42 (Rapamune) | 63–94% clinical response (n = 16–35) | Skin (65%, n = 29), mouth (75%, n = 8), liver (33%, n = 6), eye (64%, n = 11), GI (67%, n = 6) | Binds to FKBP-12 and mTOR (mammalian target of rapamycin) to inhibit cytokine-driven T cell proliferation | Hypertriglyceridemia, renal insufficiency, cytopenias, infection | 41% survival at 2 years; 89% survival at 3 years | 7 | 4 |
| 2-deoxycoformycin43 (Pentostatin) | 53% major response rates, 2% minor response (N = 58) | Lichenoid skin (69%, n = 39), sclerotic skin, fascial, mouth (52–57%, n = 39) | Nucleoside analog that inhibits adenosine deaminase (ADA) | Nausea, vomiting, infection, renal dysfunction, rash, headache | 78% survival at 1 year | 2 | 7 |
| Tacrolimus (Prograf)44,45 | 35% response rate (N = 39) | Binds to FKBP-12 (FK binding protein) and inhibits T lymphocyte activation, concentrates in liver | Renal dysfunction, thrombotic microangiopathy, neurotoxicity, hypertension | Survival not reported | 12 | 7 | |
| Less common agents | |||||||
| Rituximab (Rituxan)46,47 | 65–70% response rate (N = 21–38) | Skin (63%, n = 28), mouth (48%, n = 21), eyes (43%, n = 14), liver (25%, n = 12), lung (38%, n = 8) | Chimeric anti-CD20 monoclonal antibody | Allergic reactions, infections, hepatitis reactivation | 76% survival at 2 years | 2 | 1 |
| Thalidomide48 –50 | 20–38% response rate (N = 23–80) | Skin (46%, n = 30), mouth (22%, n = 14); joint (78%, n = 14), lung (0%, n = 6) | Anti-inflammatory and immunosuppressive properties | Neuropathy, somnolence, constipation, neutropenia | 41% survival at 2 years | 2 | 0 |