title: [The effect of lenalidomide on rare blood disorders: Langerhans cell histiocytosis, multicentric Castleman disease, POEMS syndrome, Erdheim-Chester disease and angiomatosis].
abstract: Lenalidomide has been licenced for the treatment of multiple myeloma and, in 2012, it is used as a standard treatment of relapses of the disease. Literature contains a number of publications on the effects of lenalidomide in myelodysplastic syndrome, in malignant lymphomas and chronic B lymphocytic leukaemia. The effects of the drug in rare diseases, however, have not been investigated so far. In this paper, we summarize our experience with lenalidomide in rare blood disorders. We observed an excellent effect of lenalidomide in multifocal aggressive, repeatedly relapsing Langerhans cell histiocytosis where it led to complete remission. This patient was treated with 2-chlorodeoxyadenosine and with CHOEP (cyclophosphamide, etoposide, doxorubicin, vincristine and prednisone) chemotherapy and high dose BEAM chemotherapy with autologous transplantation of haematopoietic tissue for an early disease relapse. Following another early relapse, the patient was treated with lenalidomide (25 mg). Treatment with lenalidomide induced complete remission on PET-CT. The patient was consolidated during the remission with a reduced intensity conditioning regimen and allogeneic transplantation of haematopoietic tissue. Following allogeneic transplantation, the patient has been in full remission for 10 months. We further showed an excellent effect of lenalidomide in multicentric Castleman disease with generalized involvement of lymphatic nodes, B symptoms and vasculitis. The patient was first treated R-CHOP chemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone). Due to a lack of efficacy, this was changed to the CVD combination (cyclophosphamide, thalidomide, dexamethazone). This treatment delivered complete remission but was complicated by thalidomide-associated neuropathy. Due to persistent neuropathy, thalidomide could not be used to manage further relapse and thus lenalidomide (25 mg, 11 cycles) was used. The patient has been in complete PET-CT remission for 7 months following this treatment. We observed partial efficacy in Erdheim-Chester disease. We used 2-chlorodeoxyadenosine as part of initial treatment that delivered partial regression of brain infiltrates only; fluorodeoxyglucose accumulation in the bones has not changed. Lenalidomide 25 mg was used as second line treatment. This led to complete regression of CNS infiltrates on MRI but fluorodeoxyglucose accumulation in bone lesions did not change. Regression of clinical signs and regression of fibrosis of retroperitoneum was achieved with an ongoing treatment with anakinra. A patient with multiple angiomatosis affecting the abdominal cavity, mediastinum and vertebrae and digestive tract had been stabilized with zoledronate (4 mg once every 2 months) and thalidomide (100 - 200 mg/den) for several years. However, several years of this treatment led to severe neuropathy. Consequently, we attempted to substitute thalidomide for lenalidomide. However, 10 mg of lenalidomide alone was not sufficiently effective and thus low dose of 50 mg of thalidomide was added. Combined treatment with zoledronate, lenalidomide 10 mg/day and thalidomide 50 mg/day stabilized the condition for 9 months. Due to relapsed gastrointestinal bleeding the treatment had to be changed after 9 months to thalidomide 100 mg/day and Sandostatin 0.1 mg twice daily s.c. A patient with osteosclerotic myeloma and POEMS syndrome was initially treated with CAD chemotherapy (cyclophosphamide, adriamycine and dexamethazone) that was followed by tandem high dose chemotherapy (melphalan 100 mg/m2) and autologous transplantation. Treatment with thalidomide was given due to insufficient efficacy but was not tolerated. Lenalidomide was administered as the fourth line treatment. Even though literature describes remission of POEMS syndrome following lenalidomide, four cycles did not lead to remission in our patient.
  
  
  CONCLUSIONS
  We showed an effect of lenalidomide in Langerhans cell histiocytosis and in Castleman disease. The treatment led to regression of brain infiltrates in a patient with Erdheim-Chester disease. A dose of 10 mg of lenalidomide daily in combination with 50 mg of thalidomide stabilized a course of angiomatosis. Lenalidomide did not deliver the required treatment response in a patient with POEMS syndrome and multiple previous therapies.
authors.affiliation: Interni hematologicka a onkologicka klinika Lekarske fakulty MU a FN Brno pracoviste Bohunice. a.adam@fnbrno.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Adam
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.forename: M
authors.initials: M
authors.lastname: Krejčí
authors.forename: L
authors.initials: L
authors.lastname: Zahradová
authors.forename: P
authors.initials: P
authors.lastname: Szturz
authors.forename: R
authors.initials: R
authors.lastname: Koukalová
authors.forename: Z
authors.initials: Z
authors.lastname: Rehák
authors.forename: T
authors.initials: T
authors.lastname: Nebeský
authors.forename: R
authors.initials: R
authors.lastname: Hájek
authors.forename: Z
authors.initials: Z
authors.lastname: Král
authors.forename: J
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000368:Aged; D005871:Castleman Disease / Q000188:drug therapy*; D031249:Erdheim-Chester Disease / Q000188:drug therapy*; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D016878:POEMS Syndrome / Q000188:drug therapy*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide