Correspondence
2-Chlorodeoxyadenosine to Treat Refractory Histiocytosis X
N Engl J Med 1993; 329:734-735September 2, 1993
- Article
To the Editor:
Treatment of histiocytosis X is palliative at best. It includes corticosteroids, alkylating agents, antimetabolites, vinca alkaloids, and irradiation1. Since 2-chlorodeoxyadenosine, a purine substrate analogue active against lymphoid cancers,2 is toxic to monocytes in vitro,3 and since tissue histiocytes are derived from circulating monocytes as they move from the intravascular space to soft tissues, we administered 2-chlorodeoxyadenosine to a patient with histiocytosis X.
A 33-year-old woman had presented at the age of 15 years with polyuria and polydipsia due to diabetes insipidus. Two years later vesiculopustular lesions developed on her gingiva, scalp, and vagina that were histologically consistent with a diagnosis of histiocytosis X. High-dose steroid therapy was administered, with improvement. The cutaneous lesions were treated with vinblastine; they responded at first but later became refractory. Oral etoposide, vincristine, cyclophosphamide, and methotrexate were administered, without benefit.
Before treatment with 2-chlorodeoxyadenosine, the patient had numerous vesiculopustular lesions of 3 to 4 mm and shallow ulcers of her scalp, oral mucosa, vagina, and external auditory canals. Liver function was normal, the white-cell count was 5500 per cubic millimeter with a normal differential count, the hemoglobin concentration was 123 g per liter, and the platelet count was 202,000 per cubic millimeter. The marrow was normocellular, a computed tomographic scan of the abdomen showed no hepatosplenomegaly or lymphadenopathy, and a bone survey was normal.
Four courses of 2-chlorodeoxyadenosine (0.1 mg per kilogram of body weight per day for 7 days by continuous intravenous infusion) were administered every 28 to 35 days. The second course was delayed by the development of dermatomal herpes zoster and was later complicated by transient grade 3 neutropenia (absolute neutrophil count, <500 to 1000 per cubic millimeter). The patient has been in unmaintained complete remission for more than 17 months, with no cutaneous or mucosal lesions. On follow-up, the white-cell count was 4500 per cubic millimeter with a normal differential count, the hemoglobin concentration was 128 g per liter, and the platelet count was 166,000 per cubic millimeter. The patient is now two months post partum, having delivered a normal 5 1/2-lb (2.5-kg) girl by cesarean section.
During each course of 2-chlorodeoxyadenosine blood monocytes disappeared completely (Figure 1Figure 1
Median Absolute Peripheral-Blood Monocyte Count after Four Courses of Infused 2-Chlorodeoxyadenosine.). The median absolute monocyte count was 280 per cubic millimeter before treatment (range, 90 to 380), 90 after 48 hours of 2-chlorodeoxyadenosine treatment (range, 50 to 330), and 0 on day 7 during all four courses.2-Chlorodeoxyadenosine, uniquely able to destroy resting and dividing cells4 and potently toxic to monocytes,3 offers advantages in the treatment of monocyte-derived neoplasms and chronic inflammatory conditions. The potential activity of this drug in the treatment of histiocytic diseases is encouraging and warrants further investigation in Langerhans'-cell histiocytosis, hemophagocytic histiocytosis, and other related disorders.
4 ReferencesAlan Saven, M.D.
Michael L. Figueroa, M.D.
Lawrence D. Piro, M.D.
Scripps Clinic and Research Foundation, La Jolla, CA 92037Joseph D. Rosenblatt, M.D.
UCLA, Los Angeles, CA 900241
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- Citing Articles (16)
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Toshihiko Imamura, Takashi Sato, Yoko Shiota, Hirokazu Kanegane, Kazuko Kudo, Shinichirou Nakagawa, Hisaya Nakadate, Hisamichi Tauchi, Junji Kamizono, Akira Morimoto. (2010) Outcome of pediatric patients with Langerhans cell histiocytosis treated with 2 chlorodeoxyadenosine: a nationwide survey in Japan. International Journal of Hematology 91:4, 646-651
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Girish Dhall, Jonathan L. Finlay, Ira J. Dunkel, Lawrence J. Ettinger, Stewart J. Kellie, Jeffrey C. Allen, R. Maarten Egeler, Robert J. Arceci. (2008) Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine. Pediatric Blood & Cancer 50:1, 72-79
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Hubert Mottl, Jan Starý, Markéta Cháňová, Michaela Nekolná, Eva Drahokoupilová, Vratislav Šmelhaus. (2006) Treatment of recurrent Langerhans cell histiocytosis in children with 2-chlorodeoxyadenosine. Leukemia & Lymphoma 47:9, 1881-1884
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Kimo C. Stine, Robert L. Saylors, Suzanne Saccente, Kenneth L. McClain, David L. Becton. (2004) Efficacy of continuous infusion 2-CDA (cladribine) in pediatric patients with Langerhans cell histiocytosis. Pediatric Blood & Cancer 43:1, 81-84
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