Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

INTRODUCTION: Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. CASE DESCRIPTION: In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. CONCLUSION: Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

Low molecular weight heparins for thromboprophylaxis during induction chemotherapy in patients with multiple myeloma.

BACKGROUNDS: Patients with multiple myeloma have a high risk of venous thromboembolism (VTE), especially during the induction chemotherapy. The aim of our observational study was to determine the impact of prophylaxis with low molecular weight heparin (LMWH) on the incidence of thromboembolic complications. PATIENTS AND METHODS: We analyzed the incidence of thromboembolic events in 258 patients treated with induction chemotherapy containing vincristin, doxorubicin or idarubicin, and dexamethasone, followed by stimulation chemotherapy with cyclophosphamide and G-CSF, and high-dose chemotherapy with melphalan. Two groups of these patients were compared based on the practice of thromboprophylaxis. Patients in the first group (Control, n = 140) were either not treated or treated with a short duration of anticoagulation therapy while the patients in the second group (Prophylactic, n = 118) underwent standard prophylaxis with LMWH throughout the entire period of induction chemotherapy. A total of 102 patients were selected for a close monitoring of the prophylactic effect of different LMWH doses and to be compared to patients without treatment. RESULTS: Standard prophylaxis with LMWH significantly (p < 0.007) lowered a risk of VTE when compared to patients without such prophylaxis (3.4% versus 12.9%, respectively). Furthermore, analysis of the subgroup of 102 patients revealed that higher LMWH doses (> 70 IU/kg per day) achieved full prophylaxis in 28 patients while lower doses were less effective leading to DVT in 3 (7.7%) out of 39 patients. In contrast, VTE was diagnosed in 5 (14.3%) out of 35 patients without any LMWH prophylaxis. CONCLUSION: Prophylaxis with LMWH leads to a significant reduction of the risk of thromboembolic complications during the induction chemotherapy in patients suffering from MM. The prophylactic effect of LMWH is dose-dependent.

[A patient with AL amyloidosis and severe factor X deficiency has been in complete haematological remission with normal factor X activity for 7 years following high-dose chemotherapy. A case study and literature review]. / Pacientka s AL-amyloidózou a závazným deficitem faktoru X je po vysokodávkované chemoterapii jiz 7 let v kompletní hematologické remisi s normální aktivitou faktoru X. Popis prípadu a prehled literatury.

Disturbance of haemostasis and bleeding are rather frequent complications of AL amyloidosis. These are frequently caused by increased fragility of capillaries, thrombocyte function disorders and coagulation cascade defects. The most frequent coagulation disorder is decreased factor X activity. We describe a 34-year old female after hysterectomy for myomatous uterus and metrorhagia. Before the surgery, the attending physicians did not identify any pathological changes suggesting a need for further investigations or presence of AL amyloidosis. Post-surgery development was complicated by life-threatening diffuse haemorrhage. Extended investigations of coagulation cascade revealed reduction of factor X activity to 16%. Targeted histological examination of the resected uterus confirmed AL amyloid deposits consisting of kappa chains. The patient's bone marrow contained certain small level of multiplied kappa chains-expressing plasma cells (< 10%); monoclonal immunoglobulins IgG K and free kappa chains were identified in serum. At that time, the patient did not satisfy the then valid Durie-Salmon criteria for multiple myeloma and thus the patient was diagnosed with primary systemic AL amyloidosis. The patient's condition gradually improved following substitution therapy (Prothromplex, fresh frozen plasma and erythrocyte transfusion) and bleeding slowly ceased so that chemotherapy with VAD (vincristine, adriamycin and dexamethasone) was initiated 6 weeks after the surgery. A total of 8 chemotherapy cycles were administered and complete haematological remission was achieved after the 5th cycle. Administration of the 8 VAD chemotherapy cycles resulted in increased factor X activity; bleeding complications subsided completely, thereby decreasing the risk of life-threatening mucositis-associated haemorrhage. Consequently, tandem high-dose chemotherapy (melphalan 100 mg/m2) with autologous haematopoietic stem cells transplantation was added to the treatment plan. Treatment was completed at the beginning of 2003 and, from that time, the patient is on continuous maintenance therapy with interferon alpha. Seven years from the diagnosis and 6 years from the completion of treatment the patient is in complete haematological remission, with no signs of organic damage caused by AL amyloid and with normal factor X activity. Factor X activity increased at the time when complete haematological remission was achieved after 8 cycles of VAD chemotherapy to 42%, it reached 68% the second year following high-dose chemotherapy, 77% after 5 years and 85% after 7 years. We had considered administration of high-dose chemotherapy in the standard regimen, i.e. following 4 cycles of VAD chemotherapy, as too high risk in the described young female patient. Therefore, we administered 8 cycles of conventional chemotherapy and only after complete haematological remission and partial organ response (factor X activity increased to 42%) were achieved, we added tandem high-dose chemotherapy to the treatment. We thus achieved long-term (7-years so far) complete haematological and organ remission. Increase in factor X activity is explicit over the entire 7-year observational period. We recommend starting treatment of high-risk transplant patients with AL amyloidosis with traditional chemotherapy regimen and, in case of positive haematological and organ treatment response, we recommend re-examination of potential benefits and risks of high-dose chemotherapy with autologous transplantation.

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma]. / Kvalita zivota a tolerance udrzovací lécby u pacientu s mnohocetným myelomem. Ceska myelomova skupina.

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group]. / Autologní transplantace periferních hemopoetických bunek a následná udrzovací terapie interferonem alfa nebo interferonem alfa a dexamethasonem u nemocných s mnohocetným myelomem--prubezné výsledky randomizované klinické studie 4W Ceské myelomové skupiny.

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.