Langerhans Cell Histiocytosis Treatment - Treatment of Adult LCH
Another approach using anti-inflammatory agents (pioglitazone and rofecoxib) coupled with trofosfamide in a specific timed sequence was successful in two patients with disease resistant to standard chemotherapy treatment.
Treatment of single-system skin disease
Localized lesions can be treated by surgical excision, but as with bone, mutilating surgery, including hemivulvectomy, should be avoided unless the disease is refractory to available therapy.
Topical therapies are described in greater detail in the childhood isolated skin involvement section of this summary and include topical or intralesional corticosteroid, topical tacrolimus, imiquimod, and psoralen and long-wave ultraviolet radiation (PUVA). Therapies such as PUVA may be more useful in adults where long-term toxicity may be less of a consideration.[10,11,12]
Systemic therapy for severe skin LCH includes oral methotrexate, oral thalidomide, oral interferon-alpha, or combinations of interferon and thalidomide.[13,14] Recurrences after stopping treatment may occur but may respond to retreatment.
Oral isotretinoin has achieved remission in some refractory cases of skin LCH in adults.
Chemotherapy for the treatment of single-system and multisystem disease
Chemotherapy is generally used for skin LCH associated with multisystem disease in adults.
Etoposide has been used with some success in single-system and multisystem LCH. Use of prolonged oral etoposide in adults with skin LCH has been reported with minimal toxicity, while 3-day courses of intravenous (IV) etoposide 100 mg/m2 /day achieved complete remission in a small number of patients with resistant single-system and multisystem disease. Another study at the same center found that azathioprine was the most successful drug for localized disease in adults with the addition of etoposide for refractory and multisystem disease.
For patients who do not respond to front-line therapy with etoposide, 2-CdA is effective for adults with skin, bone, lymph node, and probably pulmonary and central nervous system (CNS) disease.[18,19,20] The first study that used 2-CdA to treat refractory and recurrent disease reported on 16 patients with a median age of 44 years (range 19-72 years) who received one to six courses (median three courses) of 2-CdA at 0.14 mg/kg intravenously over 2 hours/day for 5 days. Most had localized disease: skin (n = 10), bone (n = 6), lung (n = 6), adenopathy (n = 5), or diabetes insipidus (n = 4). Complete response was seen in 44% of patients and partial response in 19% of patients for an overall response rate of 63%. Five of seven complete response patients remained in remission at 97.1 or more months. Leukopenia was the major toxicity seen in 50% of patients.[21,22]Three patients developed a second malignancy which may not be more than expected for this population group as five malignancies were found in 52 adult LCH patients in a series from Germany. Similar to children, 2-CdA clearly has activity in single-system and low-risk multisystem disease but the number of courses should be limited in view of the potential for cumulative and sometimes long-lasting myelosuppression and immunosuppression. As discussed earlier, higher dose 2-CdA combined with high-dose cytosine arabinoside appears to be the best salvage protocol to date for refractory high-risk childhood LCH, but the combination, which requires acute myeloid leukemia-type supportive care, may be too toxic for elderly adults.
An adult lymphoma treatment regimen, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin), was used in three patients with multisystem LCH and four with single-system multifocal bone LCH from 1995 to 2007. Total duration of therapy was 12 weeks, response was seen in all patients, two with partial response and five with complete response. Three recurrences were seen after stopping therapy. Despite the small number of patients and the retrospective nature of the study, MACOP-B may be useful as salvage therapy in adult patients with LCH and deserves further study.
Anecdotal reports have described the successful use of the bisphosphonate pamidronate in controlling severe bone pain in patients with multiple osteolytic lesions.[4,5,6]
Imatinib mesylate has been effective in the treatment of four adult LCH patients who had skin, lung, bone, and/or CNS involvement.[26,27] Another adult LCH patient did not respond to imatinib mesylate.