Treatment strategies for patients with RDD
| Treatment . | Dose/schedule . | Indication . | Supportive evidence . | Comments . |
|---|---|---|---|---|
| Observation | NA | Uncomplicated adenopathy | Case series of 80 patients showed 50% spontaneous remission67 | Can consider observation for near-complete resection of unifocal lesions with minimal residual disease after surgery |
| Asymptomatic cutaneous RDD | ||||
| Postoperatively for resected unifocal disease | ||||
| Corticosteroids | Prednisone: 40-70 mg or 1 mg/kg per d followed by taper | Symptomatic nodal or cutaneous disease | Several case reports and case series with prednisone showing responses in orbital, CNS, and bone RDD and AHA-associated disease69,70 | Responses, when favorable, are unpredictable in their durability |
| Dexamethasone: 8-20 mg per d followed by taper | Nonresectable or multifocal extranodal disease requiring systemic treatment | Dexamethasone was effective in CNS and nodal RDD in case reports71,72 | Optimal duration of treatment is not known because early relapse can occur | |
| Case report of intralesional steroids in orbital RDD74 | One reasonable approach is to treat to optimal response followed by slow taper | |||
| No response to steroids in other case reports of orbital, tracheal, renal, or soft tissue RDD75,76 | After successful steroid treatment: consider second-line agents to maintain response | |||
| Surgical resection | NA | Unifocal extranodal disease | Case series with long-term remission after resection of isolated cutaneous and intracranial disease31,69 | Local recurrences can occur,31,43 for which case systemic treatment should be considered |
| Symptomatic cranial, spinal, sinus, or airway disease | ||||
| Sirolimus | 2.5 mg/m2 per d for 18 mo, then taper off over 6 mo | Prolonged CR in RDD with autoimmune cytopenia77 | Reasonable first choice in ALPS-associated RDD | |
| Radiotherapy | 30-50 Gy, lymphoma-like schedule102 | Refractory or symptomatic disease not amenable to resection, recurrent after resection, or with a contraindication to systemic therapy | Palliative benefit in case reports, including refractory soft tissue and orbital RDD with visual compromise97 and for mass effect causing airway obstruction67,103 | No established fractionation schedule |
| Can also be considered as adjuvant treatment after resection of cranial or spinal lesions with residual but not bulky disease | ||||
| Chemotherapy | ||||
| Cladribine | 5 mg/m2 per d for 5 d, every 28 d for up to 6 cycles | Severe, disseminated, or refractory disease | 11 patients reported: 7 with CR, 1 with PR, and 3 with PD13,51,90-92 | Can cause myelosuppression with associated infections |
| CNS involvement | ||||
| MTX or 6-MP/MTX | 20 mg/m2 per wk of MTX, alone or with 6-MP (50 mg/m2 per d) or steroids | Multifocal, skin, or CNS RDD | PR or CR in refractory cases79-85 | Reasonable as maintenance therapy after surgery or steroids |
| Optimal duration unknown | ||||
| Vinca alkaloids | Standard doses; vinblastine usually combined with prednisone | Vincristine effective in 1 report of skin RDD86 | Variable responses | |
| Several reports showing prolonged CR when combined with other agents81-83 | Optimal duration unknown | |||
| Immunomodulatory | ||||
| Thalidomide | 50-300 mg per d; variable duration | Refractory cutaneous RDD | Recent review: several reports with prolonged CR94 | Notable toxicities include skin rash and neuropathy |
| Variable responses | Optimal dose and duration unknown | |||
| Lenalidomide | Not known | Refractory disease | Sustained CR in an adult with multiply relapsed RDD95 | Myelosuppressive but less neuropathy and skin rash than thalidomide |
| Rituximab | 500 mg/m2 per dose every 1 or 2 wk for 2-6 cycles | For refractory nodal and immune-related RDD | Efficacy described in single case reports96 | Mechanism of efficacy is not understood |
| - alone or with chemotherapy | There are reports of refractoriness and relapses,85,97 and therefore, reports of success are interpreted with caution | |||
| Imatinib mesylate | 400-600 mg per d for 7 mo | Refractory/relapsed RDD | Anecdotal activity in 1 adult with refractory RDD98 | Variable responses |
| 1 case of skin RDD was refractory99 | May work only in PDGFRα/β+ cases | |||
| Clinical trial (experimental) | ||||
| Cobimetinib (NCT02649972) | Per trial guidelines | Refractory RDD | Substantial regression of abdominal masses in a single patient with KRAS p.G12R–mutated RDD101 | Several case reports of successful treatment of ECD with cobimetinib10,100 |
| Clofarabine (NCT02425904) | 25 mg/m2 per d for 5 d, every 28 d for 6 cycles | Severe, disseminated, or refractory disease | 3 patients: 2 with CR, 1 had PR93 | Myelosuppressive and expensive |
| CNS involvement | Prospective studies ongoing to determine optimal dosing, long-term efficacy, and toxicity |
| Treatment . | Dose/schedule . | Indication . | Supportive evidence . | Comments . |
|---|---|---|---|---|
| Observation | NA | Uncomplicated adenopathy | Case series of 80 patients showed 50% spontaneous remission67 | Can consider observation for near-complete resection of unifocal lesions with minimal residual disease after surgery |
| Asymptomatic cutaneous RDD | ||||
| Postoperatively for resected unifocal disease | ||||
| Corticosteroids | Prednisone: 40-70 mg or 1 mg/kg per d followed by taper | Symptomatic nodal or cutaneous disease | Several case reports and case series with prednisone showing responses in orbital, CNS, and bone RDD and AHA-associated disease69,70 | Responses, when favorable, are unpredictable in their durability |
| Dexamethasone: 8-20 mg per d followed by taper | Nonresectable or multifocal extranodal disease requiring systemic treatment | Dexamethasone was effective in CNS and nodal RDD in case reports71,72 | Optimal duration of treatment is not known because early relapse can occur | |
| Case report of intralesional steroids in orbital RDD74 | One reasonable approach is to treat to optimal response followed by slow taper | |||
| No response to steroids in other case reports of orbital, tracheal, renal, or soft tissue RDD75,76 | After successful steroid treatment: consider second-line agents to maintain response | |||
| Surgical resection | NA | Unifocal extranodal disease | Case series with long-term remission after resection of isolated cutaneous and intracranial disease31,69 | Local recurrences can occur,31,43 for which case systemic treatment should be considered |
| Symptomatic cranial, spinal, sinus, or airway disease | ||||
| Sirolimus | 2.5 mg/m2 per d for 18 mo, then taper off over 6 mo | Prolonged CR in RDD with autoimmune cytopenia77 | Reasonable first choice in ALPS-associated RDD | |
| Radiotherapy | 30-50 Gy, lymphoma-like schedule102 | Refractory or symptomatic disease not amenable to resection, recurrent after resection, or with a contraindication to systemic therapy | Palliative benefit in case reports, including refractory soft tissue and orbital RDD with visual compromise97 and for mass effect causing airway obstruction67,103 | No established fractionation schedule |
| Can also be considered as adjuvant treatment after resection of cranial or spinal lesions with residual but not bulky disease | ||||
| Chemotherapy | ||||
| Cladribine | 5 mg/m2 per d for 5 d, every 28 d for up to 6 cycles | Severe, disseminated, or refractory disease | 11 patients reported: 7 with CR, 1 with PR, and 3 with PD13,51,90-92 | Can cause myelosuppression with associated infections |
| CNS involvement | ||||
| MTX or 6-MP/MTX | 20 mg/m2 per wk of MTX, alone or with 6-MP (50 mg/m2 per d) or steroids | Multifocal, skin, or CNS RDD | PR or CR in refractory cases79-85 | Reasonable as maintenance therapy after surgery or steroids |
| Optimal duration unknown | ||||
| Vinca alkaloids | Standard doses; vinblastine usually combined with prednisone | Vincristine effective in 1 report of skin RDD86 | Variable responses | |
| Several reports showing prolonged CR when combined with other agents81-83 | Optimal duration unknown | |||
| Immunomodulatory | ||||
| Thalidomide | 50-300 mg per d; variable duration | Refractory cutaneous RDD | Recent review: several reports with prolonged CR94 | Notable toxicities include skin rash and neuropathy |
| Variable responses | Optimal dose and duration unknown | |||
| Lenalidomide | Not known | Refractory disease | Sustained CR in an adult with multiply relapsed RDD95 | Myelosuppressive but less neuropathy and skin rash than thalidomide |
| Rituximab | 500 mg/m2 per dose every 1 or 2 wk for 2-6 cycles | For refractory nodal and immune-related RDD | Efficacy described in single case reports96 | Mechanism of efficacy is not understood |
| - alone or with chemotherapy | There are reports of refractoriness and relapses,85,97 and therefore, reports of success are interpreted with caution | |||
| Imatinib mesylate | 400-600 mg per d for 7 mo | Refractory/relapsed RDD | Anecdotal activity in 1 adult with refractory RDD98 | Variable responses |
| 1 case of skin RDD was refractory99 | May work only in PDGFRα/β+ cases | |||
| Clinical trial (experimental) | ||||
| Cobimetinib (NCT02649972) | Per trial guidelines | Refractory RDD | Substantial regression of abdominal masses in a single patient with KRAS p.G12R–mutated RDD101 | Several case reports of successful treatment of ECD with cobimetinib10,100 |
| Clofarabine (NCT02425904) | 25 mg/m2 per d for 5 d, every 28 d for 6 cycles | Severe, disseminated, or refractory disease | 3 patients: 2 with CR, 1 had PR93 | Myelosuppressive and expensive |
| CNS involvement | Prospective studies ongoing to determine optimal dosing, long-term efficacy, and toxicity |
AHA, autoimmune hemolytic anemia; CR, complete response; 6-MP, 6-mercaptopurine; MTX, methotrexate; NA, not applicable; PD, progressive disease; PR, partial response.