Erdheim-Chester disease (ECD) is a rare non-Langerhans cells histiocytosis associated with intense immune activation. In our clinical center, an ECD patient was treated with anakinra, IL1RA ...(interleukin1 receptor antagonist), resulting in clinical improvement and major decrease of pathological fatigue. The aim of the study was to evaluate changes in cytokine profile and shift of immune cells estimated by flow cytometric analysis of ECD patient before, during initial stages of anakinra treatment as well as after treatment ceased in comparison to healthy donors.
Singleplex reactions of 19 individual cytokines from serum of ECD patient were measured by FACS array. Flow cytometric analyses were performed on peripheral blood cells.
The most striking result is substantial decrease of IL6 immediately after anakinra treatment started suggesting a major role of IL1 pathway in ECD pathophysiology. As for flow cytometric analysis, increased number of CD16+ monocytes before treatment is a new finding.
Our results suggest that IL6 may be a marker of early treatment response of ECD patients treated with anakinra.
Mastocytosis is a clonal hematopoietic disorder characterized by proliferation of abnormal mast cells in various organs including the skin, digestive system, lymph nodes, and bone marrow. We report ...on a 75-year-old woman presenting with abdominal pain, vomiting, diarrhoea, myalgia, and weight loss. Abdominal CT showed hepatosplenomegaly with heterogeneous splenic parenchyma, lymphadenopathy, and osteopenia with areas of osteosclerosis but no primary tumour. An
F-FDG PET/CT revealed an overall low metabolic activity of the lesions with a diffuse bone marrow involvement raising suspicion of a haematological neoplasm. Subsequently, bone marrow and peripheral blood examinations confirmed the diagnosis of aggressive systemic mastocytosis.
Erdheim-Chester disease is a very rare histiocytic disease. It represents one form of juvenile xanthogranuloma in WHO classification of blood diseases. The disease often causes B symptoms, skeletal ...pain and also may cause diabetes insipidus and retroperitoneal fibrosis. Selection of therapy depends on published case reports and small clinical trials. There are no recommendations for treatment based on randomized studies. Interferon α is probably the most commonly used drug for this disease. Some remissions have been described after treatment. However, long-term interferon α application is needed which is associated with numerous side effects. There are limited experiences with clabridine in this indication. In Pubmed Medline database, we have found 3 publications dedicated to description of treatment response after cladribine in Erdheim-Chester disease and other 7 papers evaluating effect of cladribine on juvenile xanthogranuloma forms, mostly with positive outcome. Based on these 10 publications we choose cladribine as first-line treatment in our patient. The treatment started in October 2009 with combination of 2-chlorodeoxyadenosine (Litak) 5 mg/m2 sc. + cyclophosphamide 150 mg/m2 iv. + dexamethasone 24 mg iv., five days consecutively. These cycles were repeated monthly. Mentioned formula was submitted 4 times and 3 times in limited application on day 1 - 3. The reason of that was neutropenia grade 3. All symptoms disappeared after treatment. Only diabetes insipidus persisted because damage of pituitary stalk is irreversible. Therapeutic effect was monitored by PET-CT imaging, initially every 6 months, later in 12-month intervals. PET-CT imaging showed complete remission of disease and 4.5 years duration of remission after treatment. The treatment was well tolerated with no complications implying hospitalization. Only mild thrombocytopenia and neutropenia remains after 4.5 years. Based on case report and publications we consider cladribine as appropriate firs-line drug for Erdheim-Chester disease. Therapeutic failure after 3-4 cycles may suggest other options (interferon α, anakinra, vemurafenib), but only in the case if healthcare provider is willing to cover this new and more expansive treatment than therapy with cladribine.
We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night ...sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.
Spontaneous hepatic bleeding is a rare but potentially life-threatening complication of primary systemic amyloidosis. Although the liver is a common site of amyloid deposition, clinical presentation ...is usually mild or absent.
We report a case of a female patient, who had been repeatedly surgically revised because of liver rupture and hemoperitoneum. Initially, the computed tomography finding was interpreted as liver hemangioma. However, based on liver biopsy, the diagnosis had to be changed to primary systemic amyloidosis, and the patient was referred to our hematooncology department. Due to a considerably advanced disease, the patient was eligible only for palliative chemotherapy with cyclophosphamide and dexamethasone, which could not deflect the course of rapidly progressing liver destruction.
The cause behind ruptured and bleeding liver does not always need to be hemangioma but rather amyloidosis. In cases of advanced disease and in patients with contraindications for aggressive treatment, the outlook for complete hematological and organ treatment response is very limited. An early diagnosis is of utmost importance. Although liver biopsy brings the definite results, screening for monoclonal protein in serum or urine, leading to a search for AL amyloidosis, may be sufficient for diagnosis. The presence of some of the warning signs (B-symptoms such as fevers or subfebrile temperatures, fatigue, weight loss; and paraneoplastic laboratory findings such as elevated C-reactive protein and erythrocyte sedimentation rate) should raise suspicion of a lymphoproliferative disease.
Castleman disease is a non-clonal lymphoproliferative disorder with 2 clinical (unicentric, multicentric) and 4 histomorphological (hyaline vascular, plasma cell, mixed, plasmablastic) forms which ...combine creating a pleomorphic picture of this rare entity. In our work, the largest documented cohort in the Czech Republic was analyzed focusing on diagnostics and particularly on therapy.
The retrospective study (1998-2013) included 10 patients, 6 males, 4 females. Patients with unicentric form (3) underwent surgical sanitation. Patients with multicentric form (7) were followed-up only (2) or extirpation of the largest mass was carried out (1) or a systemic therapy was administered (4) which comprised the following regimens: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), CTD/CAD/CVD (cyclophosphamide, thalidomide/adriamycin/bortezomib, dexamethasone), further including monotherapies with tocilizumab, thalidomide and lenalidomide and in one case (associated POEMS syndrome, i.e. polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) autologous stem cell transplantation after melphalan conditioning was performed. During treatment response monitoring, all patients underwent PET/CT examination (fluorodeoxyglucose positron emission tomography/computed tomography).
The remission rate was 50% (3 unicentric forms with remission lasting 51, 8 and 9 months, resp.; 2 multicentric forms with remission lasting 3 months during thalidomide therapy and 12 months after lenalidomide therapy), stable disease was observed in 40% of cases (multicentric forms, 2 without any treatment followed-up for 171 and 24 months, resp.; 1 after systemic therapy followed-up for 23 months; 1 after two extirpations with stable lymphadenopathy for 15 years, where the first operation was 27 years ago). In one patient (10%), the associated POEMS syndrome progressed rapidly with fatal consequences (4 months follow-up).
Unlike unicentric forms completely curable by excision, multicentric forms are often treatment-refractory. Concerning high cost-effectiveness, good tolerability and documented efficacy also in rituximab-resistant cases, we prefer immunomodulatory drugs (particularly thalidomide) for managing multicentric Castleman disease in our center.
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