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On June 2006, phase II clinical trial focused on anticancer vaccination of multiple myeloma patients, was started. On September 2007, the immune and clinical response evaluation of first four patients was finished.The anticancer vaccine contained dendritic cells loaded with monoclonal immunoglobulin produced by myeloma cells. METHODS AND PATIENTS: Within the frame of phase II clinical trial were vaccinated four myeloma patients with stable disease. It was administered six vaccines for each patient, monthly. The dendritic cells were cultured from the patient's peripheral blood mononuclear cells and loaded with autologous monoclonal immunoglobulin under the good manufacturing practice conditions. After the safety and quality control, the satisfactory vaccine was administered to the patient. The functional characteristic of dendritic cells was evaluated using flow cytometry, the immune response was evaluated using ELISpot. The clinical response was monitored using monoclonal immunoglobulin concentration in patient's sera. RESULTS AND CONCLUSION: The immune response detected using ELISpot was observed in 3/4 patients. The monoclonal immunoglobulin concentration was changeable for all twelve months, but never exceeded the range of 25% for minimal clinical response achievement. During the vaccination, no significant toxicities or negative side-effects were observed. The clinical trial is going on with vaccination other patients with multiple myeloma.

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.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.

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.

In adult patients, Langerhans cell histiocytosis (LCH) manifests most frequently with one or more osteolytic lesions or, alternatively, with pulmonary involvement with nodules and cysts or with skin lesions. Infiltration ofthe central nervous system is a rather rare sign of LCH. The LCH cells have an unexplained affinity to hypothalamus and to pituitary stalk and, consequently, central diabetes insipidus is the most frequent clinical sign of brain involvement in LCH. We describe treatment of 2 adult patients with LCH in whom central diabetes insipidus was the first sign of LCH and MR confirmed pituitary stalk infiltration. The first man was diagnosed with diabetes insipidus and pituitary stalk infiltration at 33 years of age. LCH was confirmed 2 years later by histology of verrucous lesions on the skin of perianal area. The disease affected the skin and CNS. The patient was treated with 2-chlorodeoxyadenosine (5 mg/m2 s.c. for 5 consecutive days of a 28-day cycle). No pituitary infiltration was evident on an MR image after the 4th cycle. Residual perianal infiltration was irradiated. The patient has been in complete remission for 44 months following treatment completion, although vasopressin and testosterone substitution is required. The second man was also diagnosed with diabetes insipidus and pituitary stalk infiltration at 33 years of age. Pulmonary involvement was identified with high resolution CT(HRCT) and high CD1a and S-100 positive elements with bronchoalveolar lavage. This patient further had external auditory canal infiltrations causing chronic discharge from the ears. The patient was treated with 2-chlorodeoxyadenosine as above. A follow up MR after the 4th cycle showed reduction in the infiltration diameter from 5.5 to 3.0 mm. Therefore, 2-chlorodeoxyadenosine 5 mg/m2 s.c. was combined with dexamethasone 20 mg p.o. during the 5th and 6th cycle. The MR image after treatment completion showed remission of the pituitary stalk infiltrate. External auditory canal infiltration diminished as did the nodules in pulmonary parenchyma. Nevertheless, vasopressin substitution is still required. The patient has been in complete remission for 8 months from the completion of the treatment. Pituitary stalk infiltration disappeared after the treatment with 2-chlorodeoxyadenosine in 2 patients; after 4 cycles in the first and after 6 cycles (with an addition of dexamethasone during the last 2 cycles) in the second.

Monoclonal gammopathy may manifest itself through a range of skin disorders, including plane normolipemic xanthoma and necrobiotic xanthogranuloma. The present paper describes two patients with these cutaneous symptoms. The first has extensive areas of skin affected by flat xanthomas, monoclonal gammopathy with10% infiltration of bone marrow with clonal plasmocytes and, according to PET-CT, unclear lymphadenopathy in the retroperitoneal area. The size of this lymphadenopathy (histologically no malignant infiltration and no confirmed infectious aetiology) has not changed significantly over a 4-year follow-up. Repeated PET-CT scans showed decrease in SUV value in this infiltration from 7.5 to 3.8. Four cycles of treatment with a combination of bortezomib, cyclophosphamide and dexamethasone brought neither reduction in monoclonal immunoglobulin nor change to skin morphology. We believe that the abdominal lymphadenopathy is associated with xanthomatosis but have been unable to confirm this unequivocally. The second patient is being followed up for more than 10 years, originally for MGUS, later for asymptomatic multiple myeloma. Last year, painful subcutaneous and cutaneous infiltrates, isolated on an upper limb and more frequent on lower limb, started to occur. These infiltrates are palpable. PET-CT imaging provided an excellent depiction of these infiltrates, showing no pathology on the head, chest and abdomen and no osteolytic foci on the skeleton. CT imaging showed clearly numerous infiltrates in the skin and subcutaneous tissue of lower limbs, particularly both shanks, reaching up to 2 cm in depth. The largest infiltrate, measuring 3.5 by 2 by 10 cm, was identified in the distal dorsal part of the right shank. PET imaging of lower limbs showed distinctly pathological accumulation in all infiltrates described above; the accumulation of glucose in the lower part of the right shank reached 10.0 SUV. CT images of lower limbs showed increased density saturated hypodermis even in the areas where there is no increased accumulation of 18 fluoroglucose. Following 40 Gy irradiation, the size of infiltrate in the radiated area decreased and their soreness ceased.PET-CT imaging offered information on extra-cutaneous signs of plane normolipemic xanthomas and provided excellent depiction of the areas of the skin and hypodermis affected by necrobiotic xanthogranuloma. Chemotherapy with cyclophosphamide, bortezomib and dexamethasone brought no reduction in monoclonal immunoglobulin concentration, and no reduction in plane normolipemic xanthomas. Radiotherapy targeted at large foci of xanthogranulomas led to partial regression and ceased infiltrate soreness.

Waldenström macroglobulinaemia (WM) is a disease the incidence of which is approximately 10 times lower than that of multiple myeloma. The incidence of WM is reported to be respectively 0.34 per 100,000 men and 0.7 per 100,000 women. It is one of the less aggressive lymphoproliferative diseases in which therapy is indicated only when the disease symptoms start to manifest. We present a retrospective analysis of patients with the symptomatic form of WM who were treated with chemotherapy in our centre over the last 9 years, i.e. 19 WM patients (of which 7 women and 12 men). The median age upon diagnosis of the symptomatic form of WM and start of treatment was 59 (51-78) years. The median follow up for all patients was 31 (7-121) months. The most frequent indication for WM treatment was anaemia in 57% (11/19), thrombocytopaenia in 21% (4/19), plasma hyperviscosity in 42% (8/19), symptomatic lymphadenopathy in 15% (3/19), and pathologic osteolysis in 15% (3/19) ofcases, respectively. Decrease in immunoglobulin concentration under the lower physiological limit is not referred to as a characteristic sign of WM, yet it was recorded in 7 out of 19 patients in our patient group and continued after chemotherapy, with the affected patients suffering from infections in remission more often than those with physiological values of immunoglobulins. 36% (7/19) patients were treated with R-FC (rituximab + fludarabine + cyclophosphamide) therapy, 15% (3/19) with FC therapy, 15% (3/19) with R-CHOP concluded by high-dose chemotherapy with autologous transplantation in 1 case, and 5% (1/19) with CHOP therapy. VAD (vancristine, ariamycine and dexamethasone) therapy was used in 10% (2/19) of patients and 10% (2/19) of patients were treated with oral chlorambucil. The first line of treatment achieved complete remission (CR) in 15% cases (3/15). Two patients who achieved CR were treated with R-FC, and one patient with VAD. Partial remission (PR) was achieved by 63% of patients (12/19). Minor response (MR) was achieved by 10% (2/19), and stable disease (SD) was recorded in 10% of patients (2/19) after initial treatment. The first relaps of the disease was recorded in 5 patients (2 of whom had PR and 3 MR) who achieved remission after additional lines of therapy. Thirteen patients are in the first PR. With a follow up median of 31 months (7-121), only 2 patients died from other than the underlying disease. Additional malignant disease was diagnosed in 3 patients: 1 colon carcinoma, 1 acute myeloid leukaemia (AML) and 1 myelodysplastic syndrome (MDS). All three received fludarabine and cyclophopsphamide as initial therapy. Of the three patients only the patient with MDS has survived and is now without any evidence of the presence of WM, i.e. in complete remission at 41 months after the start of therapy. High-dose chemotherapy with autologous transplantation was used in 2 cases, once as part of initial therapy and once as part of the therapy for the first relaps resistant to R-CHOP chemotherapy. It is not possible to determine the median of the first remission or the median of total survival due to the short follow up interval.

According to the criteria for multiple myeloma, systemic AL-amyloidosis may be divided into primary systemic AL-amyloidosis, where monoclonal gametopathy is present but the criteria for multiple myeloma are not satisfied, and systemic AL-amyloidosis with underlying multiple myeloma. There is a continuous transition between the two units. The present paper describes treatment of patients with established systemic AL-amyloidosis who satisfy the 2003 International Myeloma Working Groups criteria for symptomatic multiple myeloma (confirmed monoclonal immunoglobulin, clonal plasmocytes confirmed in the bone marrow and at least one clinical symptom of myeloma - confirmed amyloid). From 2009, a total of 10 patients with AL-amyloidosis and underlying multiple myeloma have been treated at our centre with combined bortezomib-containing regimens. The cohort includes 5 women and 5 men. Median age of these AL-amyloidosis patients at the diagnosis was 65.5 years. All 10 patients were treated with a combination of 3 drugs, bortezomib, cyclophosphamide and dexamethasone or bortezomib, doxorubicin a dexamethasone. Two of the 10 patients died during the first month of treatment. Treatment response cannot be evaluated in these patients. Haematological treatment response was evaluable in 8 patients only. Monoclonal immunoglobulin disappearance with negative urine and serum immunofixation and normalization of free light chain immunoglobulins was observed in six of the 8 patients. Treatment response according to the current IMWG was evaluated as very good partial remission (VGPR) as we did not perform bone marrow testing after the treatment to confirm complete remission according to the current criteria. One of the 8 evaluated patients died due to disease progression in the third month of treatment and there was no haematological treatment response in one who was considered to have a stable disease. Organ treatment response was evaluated in patients who were followed up for longer than 3 months of treatment only. Organ treatment response (reduced cardiac impairment) was not evaluable in a patient who had heart transplantation and then received chemotherapy. A total of 5 (83%) of the 6 evaluated patients fulfilled the criteria of organ treatment response.Our small cohort showed a high number of haematological treatment responses (VGPR in 75% of patients) as well as organ treatment response in patients with systemic AL-amyloidosis who were treated with bortezomib-containing treatment regimens.

We describe a case of an Erdheim-Chester disease patient. First line chemotherapy treatment with 2-chlorodeoxyadenosine did not reduce fluorodeoxyglucose accumulation in pathological lesions. The patient had continuously increased CRP values of 17-20 mg/l. The disease continued to cause subfebrile temperatures and significant fatigue that made the patient to spend most of the daytime in bed. To manage the permanently increased inflammation markers, we decided to start treatment with anakinra, successfully used in some other autoinflammatory diseases (e.g. Schnitzler syndrome). We have now been able to evaluate the first 6 months of treatment. Daily subcutaneous administration of anakinra (KineretTM 100 mg daily) led to normalization of CRP values, cessation of subfebrile temperatures and, importantly, significant reduction of fatigue. Time periods the patient was able to spend out of the bed increased significantly. Consequent to the reduced fatigue, the patient was able to perform basic household tasks he was unable to undertake without treatment. After 3 months of treatment, fatigue of the same intensity returned following a short interruption of therapy. The CRP values went up again to 12 mg/l. CRP value returned back to norm and fatigue ceased after re-initiation of daily Kineret injections. Objective treatment response was assessed by measuring the degree of fluorodeoxyglucose accumulation in pathological bone lesions. PET-CT was performed before and 3 and 6 months after anakinra initiation. Intensity of accumulation did not change significantly after the first 3 months of therapy but decreased after 6 month therapy. Follow up CT of abdominal cavity was performed at the end of the 6th month of treatment. Presented CT images from before and 6 months after the treatment evidence an obvious reduction in fibroid changes in the retroperitoneum. Daily administration of anakinra to a patient with active Erdheim-Chester disease significantly reduced intensity of fatigue and improved quality of life, led to a reduction in inflammatory markers and regression in retroperitoneal fibrotization.

Histiocytic diseases caused by proliferation and accumulation of phagocytosing macrophages (foamy macrophages) have many clinical forms. These are classified under "juvenile xanthogranuloma" within the WHO classification of blood disorders. Localized forms with benign course include normolipaemic xanthomatosis, xanthogranuloma and necrobiotic xanthogranuloma. Disseminated forms in children take a form of so called "disseminated juvenile xanthogranuloma" or Erdheim-Chester disease in adults. We describe a case of a patient who, at 53 years of age, first noticed yellow granulomas on her eyelids. The disease progressed gradually and, at 59, affects the eyelids as well as their closest surroundings. According to MR and PET-CT, the disease gradually infiltrated the inside of the orbit, orbital fat as well as extraocular muscles and started to cause exoftalmus of one of the eyes. Propagation of the xanthogranuloma into the orbit and infiltration of extraocular muscles might impair eye function. Over the last year, the patient complained of cough. Pulmonary function evaluation confirmed recent asthma bronchiale. These findings correspond to periocular xanthogranuloma associated with adult-onset asthma. No other abnormities have been shown in this patient. Exoftalmus was observed in 2011 after 6 years of monitoring with very slow progression of eyelid and extraocular infiltration. Therefore, prednisone was initiated in 2011, leading to cessation of exoftalmus. It is not known at present whether this is a permanent improvement with a suppression of histiocytary proliferation or whether this was a temporary improvement due to suppression of inflammatory changes in the xanthogranuloma with no effect on histiocytary proliferation. Progression during therapy with corticosteroids would warrant cytostatic treatment. The discussion section provides an overview of diseases caused by foamy histiocytes with illustrations and an overview of experiences with their treatment.

Erdheim-Chester disease is an extremely rarely occuring condition and thus an optimal treatment is not known. Two new cases have been diagnosed in our centre in 2008 and 2009. Both patients had diabetes insipidus, B symptoms (subfebrile to febrile states) and pain in long bones of lower limbs.Imaging showed high accumulation of fluorodeoxyglucose as well as Tc-pyrophosphate in long bones of lower as well as upper limbs, aortic wall thickening with periaortic fibrosis and perirenal fibrosis. In addition, one of the patients had multiple lesions in the brain. 2-chlorodeoxyadenosine 5 mg/m2 s.c. and cyclophosphamide 150 mg/m2 administered on days 1 to 5 in 28-day cycles were selected for the treatment of both patients. Dexamethasone 24 mg/day for 5 days was added to this treatment in the second patient. Six cycles of the treatment were planned. Both patients were prescribed bisphosphonates--zoledronate and clodronate, respectively. Treatment effect was assessed with PET-CT and MR. Following treatment completion, brain infiltrates were reduced to a small residuum in the first patient who did not anymore complain of leg pain. However, there was no reduction in fluorodeoxyglucose accumulation in bone lesions and thus treatment response was assessed as partial remission. This patient is currently receiving a second line treatment and treatment follow-up is 26 months from the diagnosis. Repeated PET-CTs in the second patient showed a significant reduction in accumulation of fluorodeoxyglucose in all pathological lesions. Febrile states and pain in long bones as well as pathological fatigue ceased after the treatment. Increased CPR and fibrinogen gradually returned to their normal levels. This response is assessed as complete remission. This patient's follow-up is 16 months from the diagnosis.Administration of 2-chlorodeoxyadenosine (5 mg/m2 s.c.) + cyclophosphamide (150 mg/m2 intravenously) and dexamethasone (24 mg/day) led to partial remission in one patient; nearly complete remission of CNS infiltrates but persistent elevation of fluorodeoxyglucose accumulation in bone lesions. Complete remission with a significant reduction in accumulation of fluorodeoxyglucose in all disease lesions with normalization of originally increased inflammatory markers and disappearance of all symptoms of the disease was achieved in the second patient.

Depending on the extent of organism affected, there is a systemic (amyloid is deposited in the interstitial space of multiple tissues and organs) and localized (amyloid is deposited in one or a few solitary lesions) form of amyloidosis. Localized forms of amyloidosis have a significantly better prognosis than the systemic ones. The respiratory tract might be affected by diffuse interstitial involvement, associated with systemic AL-amyloidosis, as well as localised involvement of respiratory tract (localised laryngotracheobronchial amyloidosis) or pulmonary parenchyma called nodular form of localized pulmonary amyloidosis. Tracheobronchial form may affect larynx and bronchial tree, and forms plaques or nodules in the epithelium of the respiratory tract. Nodular form causes spherical or irregular lesions in the pulmonary parenchyma, indistinguishable from pulmonary parenchyma metastases. We describe a two-year follow up of a patient with nodular form of pulmonary amyloidosis. The patient had multiple lesions in both lungs, clearly visible on HRCT (High Resolution Computer Tomography) that intensively accumulated fluorodeoxyglucose (FDG) during the first PET-CT. At the time of diagnosis, the largest lesion SUV for FDG accumulation was 8.2. Histochemical analysis showed that amyloid consisted of the light λ chains, i.e. AL-amyloid. Investigations to detect a systemic form of amyloidosis, if present, were negative. The patient had no monoclonal immunoglobulin either in the urine or serum (negative immunofixation) and had normal levels of free light chains in the serum. Her symptoms were previously suggestive of the Sjögrens syndrome. However, the rheumatologist consulted at the time of diagnosis of the nodular form of pulmonary amyloidosis did not find any signs of an active systemic connective tissue disorder. CRP was repeatedly normal. When systemic AL-amyloidosis was excluded, we decided to only monitor lesion development with no treatment intervention. The patient had 3 PET-CTs. CT showed that no lesions enlarged, some lesions decreased in size slightly. It should be emphasized that follow-up PET-CTs did not show increased FDG accumulation. We assume that the increased FDG accumulation in pulmonary lesions seen during the first PET-CT was due to the activity of the cells that formed this amyloid and that this activity spontaneously ceased, leading to normalization of FDG accumulation in pulmonary nodules. PET-CT is useful for monitoring of the development of pulmonary nodular amyloidosis. Normalization of originally increased FDG accumulation in amyloid lesions suggests cessation of the process of amyloid formation and is a positive prognostic sign.

We describe a case of an untreated female patient monitored over 8 years for chronic B-lymphocytic leukaemia (B-CLL). Over the 8 years, the patient has gradually developed severe kidney failure, even though the criteria for B-CLL treatment had not been fulfilled. Kidney biopsy revealed renal damage due to lamda free light chains cast nephropathy as well as an infiltration of renal parenchyma with B-CLL cells. It was not before this biopsy that the presence of monoclonal immunoglobulins has been investigated. Immunofixation identified free monoclonal lamda light chains in the serum and urine. Their serum concentration, quantified by densitometry, was 2.6 g/l and urine concentration was 0.5 g/l. A specific evaluation of free light chains in the serum revealed an extremely high concentration of free X light chains, over 4500 mg/l, and normal concentration of K free light chains, 10 mg/l. The aim of this report is to emphasise that monoclonal immunoglobulin may be present in B-CLL as well as other lymphoprolipherative diseases and that it may cause damage to organs, similar to multiple myeloma or monoclonal gammopathy of undetermined significance. The described case confirms poor prognostic value of monoclonal immunoglobulin free light chains in patients with B-CLL and usefulness of an evaluation of their presence in patients with B-CLL, particularly if the patients have increased creatinine level. The described case also highlights the need for evaluation of the presence of free light chains in the serum of all patients with unclear cause of renal failure.

Cladribine (2-chlorodeoxyadenosine) is metabolised and phosphorylated in a cell up to 2-chloroadenosine triphosphate which is the actual effective form of the drug. The greatest accumulation of 2-chloroadenosine triphosphate is in the most active cells, where activating (phosphorylation) enzyme, deoxycytidine kinase, has the highest activity, whereas inactivating enzyme (dephosphorylation), cytoplasmic 5-nucleotidase, has the lowest activity. A very good ratio of the both enzymes for high effectiveness of cladribine is in resting and proliferating lymphocytes. Therefore, cladribine is an effective medication for hairy cell leukemia, Waldenström macroglo-bulinemia but also for chronic -B-lymphocytic leukemia. However, such high concentrations of 2-chloroadenosine triphosphate are reached in some cells of histiocytic lines, in monocytes and also in Langerhans dendritic cells. That's why cladribine is highly effective medication in treating Langerhans cell histiocytosis and also in treating diseases of the juvenile xanthogranuloma group. In the paper we present a survey of published experience with cladribine in patients with Langerhans cell histiocytosis. The effectiveness of cladribine in the childhood form of Langerhans cell histiocytosis is investigated only in 1 multicentric clinical study, other data are taken from single case reports or small series studies. Cladribine was used in 60 adult patients altogether and in 51 of them (85%) treatment response (CR + PR) was achieved. In the group of childhood patients cladribine was used in 182 cases and treatment response (CR + PR) was reached in 110 (60.4%) thereof. One possible explanation for a higher number of therapy responses in adults is lower Langerhans cell histiocytosis aggressiveness in adults than in children. Another explanation is the fact that therapy responses in adults are summarized only from case reports and smaller cohorts, whereas in children, case reports and also results of a prospective randomized clinical study are included. Diseases of the juvenile xanthogranuloma group are much more rare than Langerhans cell histiocytosis and so the number of publications is smaller. In total, 7 publications describe therapy response of cladribine in some of the juvenile xanthogranuloma forms (Erdheim-Chester disease, disseminated juvenile xanthogranuloma and localized form of plane xanthoma type). Cladribine was also effective in CNS infiltration by Langerhans cell histiocytosis cells or juvenile xanthogranuloma cells.Cladribine is a highly effective medication used in treating Langerhans cell histiocytosis. It is very good tolerated in monotherapy. Therefore, it is suitable for initial therapy of adults with multifocal or multisystem form of Langerhans cell histiocytosis. Furthermore, it has the use in treating relapses after some other initial therapy. According to published experience, it is an effective drug for diseases of the juvenile xanthogranuloma group (Erdheim-Chester disease, diffuse juvenile xanthogranuloma and also Rosai-Dorfman disease).