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2-Chlorodeoxyadenosine-Induced Complete Remissions in Langerhans-Cell Histiocytosis
- Alan Saven, MD;
- Kenneth A. Foon, MD; and
- Lawrence D. Piro, MD
- From Scripps Clinic and Research Foundation, La Jolla, California and the University of Kentucky, Lexington, Kentucky. Requests for Reprints: Alan Saven, MD, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037. Acknowledgments: The authors thank Mary-Helen Hader for data collection.
Langerhans-cell histiocytosis results from the proliferation and accumulation of tissue histiocytes, clinically manifested as osteolytic lesions, hypothalamic insufficiency, and seborrheic and vesiculopustular lesions on the scalp, perineum, rectum, and vulva [1]. Treatment has been palliative and includes corticosteroids, alkylating agents, antimetabolites, vinca alkaloids, and irradiation [2]. Combination chemotherapy offers no advantage over the use of single agents and is associated with greater toxicity. 2-Chlorodeoxyadenosine (2-CdA) (cladribine, Leustatin [Ortho Biotech, Raritan, New Jersey]), a purine analog with activity in indolent lymphoproliferative disorders and myeloid leukemias [3, 4], is potently toxic to monocytes in vitro [5]. Because tissue histiocytes are derived from the same stem cells as circulating monocytes, 2-CdA was a rational therapeutic option [6]. We therefore administered 2-CdA to three patients with Langerhans-cell histiocytosis.
Methods
Patients were required to have a histologic diagnosis of Langerhans-cell histiocytosis and measurable disease. 2-Chlorodeoxyadenosine was supplied by Ortho Biotech and was administered every 28 to 35 days until maximum response or prohibitive toxicity. A complete response was defined as the absence of disease as proven by physical examination and imaging studies. Skin lesions did not require repeat biopsy to document histologic resolution. A partial response was defined as a reduction by more than 50% of all measurable disease for more than 1 month. Any response less than partial was designated as no response. Standard criteria of the Eastern Cooperative Oncology Group were used for the evaluation of toxicity [7].
Results
Patient 1
A 33-year-old woman presented at age 15 years with polyuria and polydipsia from diabetes insipidus and later developed vesiculopustular lesions of her gingiva, scalp, and vagina that were histologically confirmed as Langerhans-cell histiocytosis. High-dose steroids induced a brief, partial response. After delivering a normal infant by cesarean section, she developed painful vaginal ulcers that were treated with irradiation. The cutaneous …
