Successful treatment of two children with Langerhans' cell histiocytosis with 2'-deoxycoformycin

Langerhans' cell histiocytosis (LCH) is problematic illness with a subset of patients experiencing a relapsing or progressive course despite therapy with chemotherapy and/or immunosuppressive agents. Novel therapies are required. 2'-deoxycoformycin (2'-dCF) is an inhibitor of adenosine deaminase (ADA) and is toxic to lymphocytes and monocytes. We hypothesized that 2'-dCF might be effective in treatment of children with LCH, in part because of recent success reported with 2-chlorodeoxyadenosine. In this report we describe our experience using 2'-dCF to treat two patients with refractory LCH.

The patients, aged 5 and 3 years, had received therapy for 4 and 2.5 years, respectively, with vinblastine, corticosteroids, etoposide, methotrexate, 6-mercaptopurine, and, in one case, cyclosporine. While receiving cyclosporine, the first patient developed rapidly enlarging lytic skull lesions accompanied by pain and tenderness. While receiving methotrexate and 6-mercaptopurine, the second patient developed fever, anemia, multiple new bony lesions, and massive abdominal and axillary adenopathy, proven at biopsy to be due to recurrent LCH. Treatment in both cases was with 2'-dCF 4 mg/m2 given by intravenous push weekly for 8 weeks then continuing every 2 weeks for >21 and 16 months, respectively.

Both patients responded to 2'-dCF therapy. The first patient's pain resolved following three doses of 2'-dCF, and the skull lesions decreased in size significantly over the following 6 months. After 15 months of therapy he developed asymptomatic radiologic evidence of a possible new lesion in the femur which did not progress over the subsequent 3 months. The second patient experienced improvement at all sites of disease over 8 weeks, with complete resolution of bony lesions over the next 5 months. At 16 months from initiation of 2'-dCF therapy she remains disease-free. Toxicity was limited to asymptomatic grade III-IV lymphopenia and abnormalities of lymphocyte mitogen responses. The patients are asymptomatic and continue biweekly and monthly 2'-dCF therapy, respectively.

2'-dCF has shown activity against LCH in these two cases, with minimal toxicity. Further study of this agent in the therapy of LCH is warranted.