Sequential approach to treatment options for w-AIHA and common dosing regimens
| Treatment option . | Common dosing regimens . |
|---|---|
| First-line treatment: with the goal to support and stabilize during acute hemolysis | |
| Steroids | The first 72 hours, dose varies widely between different hematology teams from 1 to 2 mg/kg/dose of prednisone every 8-12 hours up to high-dose steroids, eg, methylprednisolone 250-1000 mg/day |
| After the first 72 hours, the dose is decreased to 1-2 mg/kg/day in children and 30-80 mg/day in adults | |
| Disease is considered responsive to steroids if stabilization of Hb to >10 g/dL within 1-3 weeks | |
| After such a response, the steroid dosing should continue for ≥6 months with a very slow wean | |
| Transfusions | Establish good communication with transfusion services to provide as needed to treat anemia |
| IVIG | Usually 1 g/kg/day × 2 days; consider when response to steroids in the acute setting is not satisfactory |
| Plasmapheresis | Consider when response to steroids in the acute setting is not satisfactory |
| Second-line treatment: in refractory disease with no or limited response to steroids and/or when steroids cannot be weaned appropriately | |
| Rituximab | Most frequently 375 mg/m2 intravenously weekly for 4 weeks but decreased dose of 100 mg intravenously weekly for 4 weeks has also been effective; caution recommended in cases of underlying immune dysregulation, eg, ALPS |
| Splenectomy | Caution recommended in cases of underlying immune dysregulation, eg, ALPS |
| Second-line treatment: when steroids cannot be weaned appropriately | |
| MMF | 600 mg/m2 by mouth twice daily37 |
| Sirolimus | 2 mg/m2 by mouth once daily (goal trough 5-15 ng/mL)37 |
| Danazol (off-label) | Initial dosages ranged from 600 to 800 mg/day (by mouth in 3-4 divided doses), with maintenance therapy of 200-600 mg/day |
| Third-line treatment: when disease relapses or remains refractory despite 2nd line treatment | |
| Azathioprine | In pediatrics used typically for w-AIHA accompanied by autoimmune hepatitis, at initial dose of 0.5 mg/kg titrated to response up to 2 mg/kg by mouth once daily |
| Adults: 1-2 mg/kg (maximum, 150 mg daily) | |
| 6-Mercaptopurine | 50-75 mg/m2 by mouth once daily (2.5 mg/kg once daily for children with body surface area under 1 m2)53 |
| Cyclosporine | 5 mg/kg/day initially, decreased after response to 2-3 mg/kg/day by mouth divided every 12 hours |
| Cyclophosphamide | Dosing used in ITP has been 1-2 mg/kg/day orally for ≥16 weeks or 300-1000 mg/m2 intravenously for 1-3 doses every 2-4 weeks56 |
| Fourth-line treatment: high risk treatment to consider as last resort | |
| High-dose cyclophosphamide | 50 mg/kg/day for 4 days followed by granulocyte colony-stimulating factor43 |
| Alemtuzumab | 3 mg intravenously or subcutaneously on day 1 and then if tolerated, 10 mg on day 2, and then if tolerated, 30 mg on day 3, continue with maintenance 10-30 mg 3 times weekly for up to 12 weeks |
| HSCT | Autologous or allogeneic has been used |
| Treatment option . | Common dosing regimens . |
|---|---|
| First-line treatment: with the goal to support and stabilize during acute hemolysis | |
| Steroids | The first 72 hours, dose varies widely between different hematology teams from 1 to 2 mg/kg/dose of prednisone every 8-12 hours up to high-dose steroids, eg, methylprednisolone 250-1000 mg/day |
| After the first 72 hours, the dose is decreased to 1-2 mg/kg/day in children and 30-80 mg/day in adults | |
| Disease is considered responsive to steroids if stabilization of Hb to >10 g/dL within 1-3 weeks | |
| After such a response, the steroid dosing should continue for ≥6 months with a very slow wean | |
| Transfusions | Establish good communication with transfusion services to provide as needed to treat anemia |
| IVIG | Usually 1 g/kg/day × 2 days; consider when response to steroids in the acute setting is not satisfactory |
| Plasmapheresis | Consider when response to steroids in the acute setting is not satisfactory |
| Second-line treatment: in refractory disease with no or limited response to steroids and/or when steroids cannot be weaned appropriately | |
| Rituximab | Most frequently 375 mg/m2 intravenously weekly for 4 weeks but decreased dose of 100 mg intravenously weekly for 4 weeks has also been effective; caution recommended in cases of underlying immune dysregulation, eg, ALPS |
| Splenectomy | Caution recommended in cases of underlying immune dysregulation, eg, ALPS |
| Second-line treatment: when steroids cannot be weaned appropriately | |
| MMF | 600 mg/m2 by mouth twice daily37 |
| Sirolimus | 2 mg/m2 by mouth once daily (goal trough 5-15 ng/mL)37 |
| Danazol (off-label) | Initial dosages ranged from 600 to 800 mg/day (by mouth in 3-4 divided doses), with maintenance therapy of 200-600 mg/day |
| Third-line treatment: when disease relapses or remains refractory despite 2nd line treatment | |
| Azathioprine | In pediatrics used typically for w-AIHA accompanied by autoimmune hepatitis, at initial dose of 0.5 mg/kg titrated to response up to 2 mg/kg by mouth once daily |
| Adults: 1-2 mg/kg (maximum, 150 mg daily) | |
| 6-Mercaptopurine | 50-75 mg/m2 by mouth once daily (2.5 mg/kg once daily for children with body surface area under 1 m2)53 |
| Cyclosporine | 5 mg/kg/day initially, decreased after response to 2-3 mg/kg/day by mouth divided every 12 hours |
| Cyclophosphamide | Dosing used in ITP has been 1-2 mg/kg/day orally for ≥16 weeks or 300-1000 mg/m2 intravenously for 1-3 doses every 2-4 weeks56 |
| Fourth-line treatment: high risk treatment to consider as last resort | |
| High-dose cyclophosphamide | 50 mg/kg/day for 4 days followed by granulocyte colony-stimulating factor43 |
| Alemtuzumab | 3 mg intravenously or subcutaneously on day 1 and then if tolerated, 10 mg on day 2, and then if tolerated, 30 mg on day 3, continue with maintenance 10-30 mg 3 times weekly for up to 12 weeks |
| HSCT | Autologous or allogeneic has been used |
For danazol and most of the third- and fourth-line treatment medications, limited data are available; dosing regimen is based on case reports or small case series for patients with w-AIHA or dosages that have been used in patients with ITP.