Adult
Langerhans cell histiocytosis (LCH) usually follows a favorable course. Very rarely, however, multi-system (multi-organ) LCH difficult to manage either with traditional first line treatment (
vinblastine,
mercaptopurine,
prednisone or
etoposide) or
2-chlorodeoxyadenosine occurs. In these patients, other treatment modalities have to be used. We describe a patient with LCH manifesting with generalized
lymphadenopathy and infiltrating the pulmonary parenchyma and skin. The disease activity was always associated with B-symptoms (
weight loss, subfebrile states, night sweats). Histological investigations repeatedly showed higher proliferation activity than that usual in adult patients with LCH. Expression of Ki-67 proliferation marker was up to 30% and there were 8-10 cells in mitosis in the microscope viewing field. Therefore,
therapy started with the application of stimulation regimen (
cyclophosphamide 2 g/m2 on day 1 and
etoposide 200 mg/m2 on days 1-3) followed by collection of peripheral blood stem cells. Then, treatment with
2-chlorodeoxyadenosine, the first 3 cycles as monotherapy of 5 mg/m2 SC on days 1-5 in 28-day cycles, the next 3 cycles in combination with
cyclophosphamide 150 mg/m2 on days 1-5 and
methylprednisolone 250 mg on days 1-5, was used. However, the disease relapsed 2 months after completion of the
therapy. This early relapse was treated with 4 cycles of CHOEP
chemotherapy (
cyclophosphamide,
doxorubicin,
vincristine,
etoposide,
prednisone). Following the 4th cycle of CHOEP, high-dose BEAM
chemotherapy (
carmustine,
etoposide,
cytarabine,
melphalan) with autologous
stem cell transplantation were administered. According to the follow-up PET-CT examination, this treatment resulted in complete disease remission. However, the disease relapsed again in the lymph nodes, lungs, skin and bones 5 months after the high-dose
chemotherapy. The progression was documented on PET-CT scanning.
Lenalidomide 25 mg daily for 21 days in 28-day cycles with
dexamethasone 20 mg once a week were administered as the 4th line treatment. After the 4th cycle of
lenalidomide, PET-CT was performed, where the CT component suggested a significant reduction (more than 50%) in the size of the lymph nodes and the PET component showed substantial reduction in fluorodeoxyglucose accumulation in the affected lymph nodes as well as in the bone lesions. HRCT showed disappearance of pulmonary nodules. During the treatment, CRP levels declined and
hemoglobin rose from 110 to 141 g/l, i.e. partial remission was achieved after 4 cycles.
Etoposide (100 mg IV) was added to
lenalidomide and
dexamethasone on days 22, 23 and 24 of the above mentioned 28-day cycle. The added
etoposide further intensified treatment response. In all, 11 cycles of this
chemotherapy were given, resulting
in complete remission confirmed by follow-up PET-CT. The achieved remission was consolidated using allogeneic
bone marrow transplantation after FLAMSA reduced intensity conditioning without
amsacrine. Four months after
allogeneic transplantation, the patient has been relapse free. Herein we presented treatment response of highly aggressive LCH to
lenalidomide. The used four cycles led to partial remission only and with the combination of
lenalidomide,
dexamethasone and
etoposide the treatment response was further intensified to complete remission.