Outcome of pediatric patients with Langerhans cell histiocytosis treated with 2 chlorodeoxyadenosine: a nationwide survey in Japan

Abstract

The aim of this study was to assess the outcome of treatment with 2-chlorodeoxyadenosine (2-CdA) in pediatric patients with Langerhans cell histiocytosis (LCH) in Japan. We retrospectively identified 17 pediatric LCH patients treated with 2-CdA. All patients were refractory or reactivated cases who had been initially treated according to the JLSG-02 protocol of the Japan LCH study group. At initiation of 2-CdA therapy, 4 patients had primary refractory multisystem (MS) disease with risk organ (RO) involvement (MS+), 9 patients had reactivated MS disease [5 MS+ and 4 without RO involvement (MS-)], and the remaining 4 patients had refractory/reactivated multifocal bone disease (MFB). Treatment with 2-CdA (4-9 mg/m(2)/day) was administered on 2-5 consecutive days and repeated every 3-4 weeks for a period that ranged from 2 to 12 months. Four primary refractory patients were treated with 2-CdA combined with high dose of cytarabine. In MS+ patients, response to treatment was observed in 5 of the 9 patients. In MS-/MFB patients, 5 of the 8 patients showed response to treatment. In the patients who were primary refractory or had reactivation during initial chemotherapy, 4 of 10 patients showed good response. On the other hand, in the patients having reactivation while off therapy, 6 of 7 patients showed good response. These findings suggest that 2-CdA is effective for reactivated LCH while off therapy.

Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning

“…Cytarabine is a drug also phosphorylated by deoxyctidine kinase and has been used successfully together with vincristine and prednisolone in children with disseminated LCH and organ dysfunction (Egeler et al , ). The main limitation of the study combining and cytarabine was the small number of patients enrolled, nevertheless the results were significantly better than the reported historical outcome for this group of patients (Imamura et al , ).…”

Recent advances in Langerhans cell histiocytosis

“…In patients who show reactivation in non‐risk organs while they are off therapy, treatment with pamidronate combined with Cox2 inhibitor or 2‐CdA monotherapy may be effective. Careful attention is required to prevent known adverse effects of therapy with 2‐CdA, namely, the development of severe persistent bone‐marrow failure and myelodysplastic syndrome .…”

Histiocytosis X: Characteristics, behavior, and treatments as illustrated in a case series

“…A recent study demonstrated the effectiveness of 2-CdA in children with recurrent LCH. [13] Recurrences are more common when the disease is multifocal than in patients presenting with disease that is confined to a solitary focal point. However, there have been reports of recurrent unifocal tumors.…”