pentostatin and Histiocytosis--Langerhans-Cell

Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH).. To assess the efficacy of 2-CdA and 2'-DCF as salvage therapy for LCH, a survey of members of the Histiocyte Society and a literature review were undertaken. Twenty-three patients treated with 2-CdA and 4 treated with 2'-DCF were found, age range 2 months to 49 years.. All 15 survey patients had multiorgan involvement, and 14 were heavily pretreated. Doses of 2-CdA ranged from 0.1 mg/kg/day continuous infusion for 5-7 days (majority of patients) to 13 mg/m(2)/day for 5 days, for 1-6 courses. One of the 15 patients had an early death, 5 had no response (NR), 3 had partial response (PR), and 6 achieved complete response (CR). Among 8 published patients, 7 achieved stable CR and 1 NR. Among 4 patients treated with 2'-DCF (4 mg/m(2)/week for 8 weeks then q 2 weekly), 2 achieved CR for 16+ and 18+ months and 2 PR for 2 and 5 months. Toxicity consisted mainly of combined myelo- and immunosuppression but no significant infections occurred and there were no toxic deaths. A cumulative thrombocytopenia was noted, which in 1 case took up to 6 months to resolve. Transient gastrointestinal toxicity and elevation of liver enzymes was seen, and 2 patients developed renal tubular acidosis. The peripheral neuropathy reported in adult patients receiving high doses was not seen.. 2-CdA and 2'-DCF appear to have a useful role in LCH and are worthy of prospective trial in patients unresponsive to routine therapy.

Topics: Adolescent; Adult; Age of Onset; Antibiotics, Antineoplastic; Antineoplastic Agents; Child; Child, Preschool; Cladribine; Data Collection; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Liver; Male; Pentostatin; Thrombocytopenia; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Cladribine; Diagnosis, Differential; Female; Goiter; Histiocytosis, Langerhans-Cell; Humans; Interferon-alpha; Middle Aged; Pentostatin; Thyroid Gland; Treatment Failure; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Child; Child, Preschool; Drug Evaluation; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Male; Pentostatin; Salvage Therapy

Topics: Enzyme Inhibitors; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Infant; Pentostatin; Remission Induction; Time Factors

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.

Topics: Antibiotics, Antineoplastic; Child, Preschool; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Male; Pentostatin