Cladribine for the Management of Erdheim-Chester Histiocytosis in Adults

Introduction: Erdheim-Chester Disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by foamy infiltrates of the soft tissue and bone, with a histopathology that demonstrates CD68-positive, CD1a-negative, and S100-negative histiocytes densely infiltrating bone, lymph nodes, retroperitoneum, and systemic vasculature. Although no therapy has been designated as standard, a variety of chemotherapeutic options exist for management in adults. Cladribine (2-chlorodeoxyadenosine) is a metabolite that predominantly affects blood cells by mimicking adenosine nucleosides, inhibiting adenosine deaminase, and thus disrupts the ability of the cell to repair DNA. In this abstract, we report three patients with varying sites of disease who achieved remission following treatment with cladribine. Although the efficacy of cladribine has been demonstrated in patients with ECD who exhibit neurological symptoms, we present three patients in whom significant responses were achieved in disease distributed in long bones, pericardium, skin, and retroperitoneum.

Case Description: Three adult patients presented for management of ECD, one after extensive prior therapy with corticosteroids, vinblastine and alpha-interferon; and two patients who had not received prior therapy. Each patient was treated with cladribine (0.14 mg/kg) administered via IV infusion two hours daily for five days on a 28-day cycle. The first patient, age 46, had disease involving skin, uveal tract, testis and retroperitoneum; he also had diabetes insipidus (DI). Previous therapy with steroids, vinblastine, and interferon had proven ineffective and had been associated with life-threatening, opportunistic infection. A second patient, age 28, presented with painful lytic bone disease, DI, and “b” symptoms consisting of fevers, chills, sweats, and progressive weight loss. A third patient, age 64, presented with recurrent episodes of pericarditis requiring placement of a pericardial window. All three patients achieved sustained disease regression after treatment with 5, 3, and 4 cycles of treatment, respectively. Treatment-related toxicity included febrile neutropenia in the first patient; all three patients received anti-PCP, anti-viral, and anti-fungal prophylaxis for one year after completing therapy, and had no opportunistic infections. The first and third patients have required no further treatment 10 years, and 17 months after completion of therapy. The second patient required re-treatment, initially with interferon, and then with Cladribine, after a symptom-free interval of 13 months, and has achieved a second remission with Cladribine.

Conclusion: The experience with these three patients illustrates the potential efficacy of cladribine for management of Erdheim-Chester histiocytosis in adults. Based on this preliminary experience, a further prospective trial in a larger group of patients with newly diagnosed Erdheim-Chester Disease seems warranted.