Cladribine as the first line treatment in multifocal or multiorgan Langerhans cell histiocytosis in adult patients

Authors: Z. Adam 1;  P. Szturz 1;  J. Ďuraš 2;  Z. Řehák 3;  R. Koukalová 3;  L. Pour 1;  M. Krejčí 1;  M. Navrátil 1;  Z. Adamová 4;  R. Hájek 1;  J. Mayer 1
Authors‘ workplace: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc. 1;  Oddělení klinické hematologie FN Ostrava, přednosta prim. MUDr. Jaroslav Gumulec, Ph. D. 2;  Oddělení nukleární medicíny a pozitronové emisní tomografie Masarykova onkologického ústavu Brno, přednosta prim. MUDr. Karol Bolčák 3;  Chirurgické oddělení Nemocnice Vsetín, přednosta prim. MUDr. Jaroslav Sankot 4
Published in: Vnitř Lék 2010; 56(Supplementum 2): 141-151
Category: Langerhans cell histiocytosis and some other Hematology rare diseases


Vinblastin and prednisone are the traditional treatment choices in Langerhans cell histiocytosis (LCH). Cladribine has also been shown to be highly effective. It was originally used as the second and higher lines treatment and achieved high treatment response. The first report on excellent results achieved with cladribine as the first line treatment was published in 2003. Based on this report and our own experience with high efficacy of cladribine when administered as the second and higher line treatment, we use cladribine since 2003 not only for adult patients with relapsing multifocal or multiorgan form of LCH but also as part of the first line treatment of multifocal and multisystemic forms of LCH.

Patients and methodology:
Ten patients (9 men and 1 woman) have been treated with cladribine since 2001. Median age at diagnosis was 31.5 (5–45) years. The disease involved multiple organs in 8 patients and had an aggressive multifocal bone-involving form in 2 patients. Cladribine was administered in the dose of 5 mg/m2/day s.c. for 5 consecutive days in 28-day intervals. In 2 patients in whom the treatment was insufficient, the 3rd cycle of cladribine monotherapy was followed by a combination treatment with cladribine 5 mg/m2/day, cyclophosphamide 300 mg/day and dexamethasone 20 mg/day, all 1st–5th day. We planned a maximum of 6 cycles. Median of administered cladribine cycles was 5 (4–6).

In 2 patients, the disease had an aggressive character at the diagnosis, and thus a collection of haematopoietic stem cells from peripheral blood was performed before cladribine administration. In total, 9 patients have now completed their treatment and, of these, 8 (88%) are in complete remission. The treatment was ineffective in one patient only – it relapsed within 60 days from treatment completion. This patient received three cycles of the CHOEP regimen (cyclophosphamide, adriamycin, vincristine, etoposide and prednisone) and the treatment was completed with high-dose BEAM chemotherapy (carmustine, cytarabine, etoposide, melphalan). The patient has now been in complete remission for 5 months from the completion of the high-dose therapy. Treatment response was observed in all 3 patients with CNS involvement, in 2 patients with LHC focus in pituitary infundibulum and in 1 patient with LCH focus in temporal lobe.

Cladribine is a suitable treatment modality for multiorgan and multifocal forms of LCH. Complete remission was achieved in 88% of the 9 evaluable patients. Treatment response was achieved in all three patients with CNS lesions. Addition of cyclophosphamide and dexamethasone after the 4th cycle improved treatment response in 2 patients, although this response was sustained on longer term basis in one patient only. Ascertaining the usefulness of adding cyclophosphamide and dexamethasone to cladribine in patients with LCH will require evaluation of this treatment on a larger sample of patients.

Key words:
cladribine – 2-chlorodeoxyadenosine – Langerhans cell histiocytosis – diabetes insipidus


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