Original Article
2-Chlorodeoxyadenosine Therapy for Disseminated Langerhans Cell Histiocytosis

https://doi.org/10.4065/78.3.301Get rights and content

Objective

To evaluate the efficacy of 2-chlorodeoxyadenosine (2-CDA), a purine nucleoside analogue, in treating disseminated Langerhans cell histiocytosis (LCH).

Patients and Methods

We retrospectively reviewed the clinical records of 5 patients who were seen at our institution for histologically confirmed disseminated LCH, including 1 patient with central nervous system parenchymal involvement. These patients were treated consecutively with 2-CDA chemotherapy between December 1994 and January 2001. The patients ranged in age from 19 to 81 years, and the median pretreatment duration of disease was 23 months. Median follow-up after initiation of 2-CDA treatment was 33 months. 2-Chlorodeoxyadenosine was used as frontline therapy for 1 patient and as salvage therapy for the other patients. Patients generally received 0.7 mg/kg over 5 or 7 days; the median number of courses was 4.

Results

Complete responses were achieved in 3 patients, including the patient with central nervous system disease, which, to our knowledge, has not been described previously. Two other patients achieved partial responses. The overall response rate was 100%. Toxic effects consisted mainly of myelosuppression; 1 patient developed dermatomal herpes zoster infection.

Conclusion

Our experience confirms the reported efficacy of 2-CDA in the treatment of LCH; however, the optimal timing and schedule of therapy remain to be determined.

Section snippets

PATIENTS AND METHODS

Between December 1994 and January 2001, 5 patients with biopsy-proven disseminated LCH were consecutively treated with 2-CDA at the Mayo Clinic in Rochester, Minn. We retrospectively reviewed their records to assess for clinical response to 2-CDA therapy, after obtaining approval from the Mayo Foundation Institutional Review Board. The ages of the 3 men and 2 women ranged from 19 to 81 years, and the median pretreatment duration of disease was 23 months (range, 4-24 months). In one patient,

Case 1

A 38-year-old man presented with a 2-week history of progressive headaches. Magnetic resonance imaging of the brain showed an irregular, enhancing mass involving the right caudate nucleus with considerable surrounding edema associated with mass effect and midline shift (Figure 1). Pathologic review of tumor tissue obtained by stereotactic biopsy confirmed LCH (Figure 2). The patient was given high-dose corticosteroids, subsequently underwent primary external beam radiation therapy (2.035 Gy in

DISCUSSION

For patients with LCH who have refractory or relapsed disease or those with widespread multiorgan involvement and rapid progression of disease, new and effective therapies are necessary.

Among antimetabolites, 2-CDA is novel in that it appears to have activity against both resting and actively dividing lymphocytes.12 Its ability to induce apoptosis in lymphocyte populations with low growth fractions is thought to underlie its substantial clinical activity in indo lent lymphoproliferative

CONCLUSION

The developing opinion is toward the use of 2-CDA for refractory or relapsed LCH or even as first-line therapy for patients with high-risk disease, although the latter practice is not universally accepted because of the potential for acute and long-term toxic effects associated with this agent. 2-Chlorodeoxyadenosine is potently immunosuppressive, and its incorporation into DNA renders it potentially mutagenic.8 Sustained follow-up of patients is required for an accurate assessment of the

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