Bone marrow and peripheral blood leptin levels in lymphoproliferative diseases--relation to the bone marrow fat and infiltration.

Leptin is a nonglycosylated protein produced mostly by adipocytes. The role ofleptin in body weight regulation through its anorectic effect in hypothalamus is very well known. Less known are other leptin effects such as the stimulation of hematopoesis and some parts of immunity system. The role of leptin in the pathogenesis of some malignant tumors is discussed. Only a little is known about bone marrow adipocyte leptin production. We examined leptin concentrations in the sera from peripheral blood and bone marrow, the percentage of bone marrow fat, the degree of bone marrow infiltration, the body mass index (BMI) in 42 patients with lymphoproliferative diseases. We found that bone marrow has significantly lower leptin levels (6,6+/-10,9 ng/ml) than peripheral blood (9,1+/-11,5 ng/ml) (p < 0.0001). Bone marrow and peripheral blood leptin levels have also a significant thin correlation (r = +0.91, p < 0.0001). Bone marrow (r = +0.55, p < 0.0005) and peripheral blood (r = +0.52, p < 0.0005) leptin concentrations are significantly correlated to BMI. Blood serum leptin (r = +0.46, p < 0.003) and bone marrow leptin (r = +0.40, p < 0.01) are related to the bone marrow fat percentage. In addition we found a negative correlation of blood serum leptin (r = -0.59, p < 0.0001) and bone marrow leptin (r = -0.42, p < 0.005) to bone marrow malignant infiltration. When we divided the patients into groups with bone marrow infiltration more than 10% and without or less than 10% infiltration, the first group had significantly lower peripheral blood (p < 0.001) and bone marrow (p < 0.02) leptin. We also confirmed a relation of bone marrow fat and infiltration (r = +0.49, p < 0.001). Our results suggest a relationship among leptin levels in blood or bone marrow and bone marrow infiltration in lymphoproliferative diseases. This fact needs further investigation and an evaluation of its application in clinical practice.

Pulmonary sarcoidosis in a patient with essential thrombocythemia treated with interferon alpha: a short case report.

A patient with essential thrombocythemia was diagnosed with pulmonary sarcoidosis after interferon alpha therapy. Following interferon treatment the miliary pulmonary dissemination has appeared and after disruption of this therapy it resolved during two months. Few cases of sarcoidosis associated with interferon alpha treatment have been reported. These patients were treated for chronic myelogenous leukemia, chronic hepatitis C, and renal cell carcinoma. We report the first case of interferon-related sarcoidosis in an essential thrombocythemia patient.

[Leptin levels in peripheral blood and bone marrow in orthopedic patients]. / Hladiny leptinu v sérech z periferní krve a kostní drene u ortopedických pacientu.

Leptin is a protein with hormonal activity and is produced mainly by adipocytes. Its primary function in the human organism is regulation of the calorie intake via the anorectic action in the hypothalamus. Leptin participates also in the regulation of haematopoiesis and immunity processes. There are many data on leptin production by peripheral adipose tissue and it is also known that leptin is produced by adipocytes of bone marrow. It was assumed for a long time that adipocytes of bone marrow are not only a passive source of energy but have, similarly as stromal cells, a regulatory function. However, it is not clear in what way the adipose tissue of bone marrow participates in the regulation of haematopoiesis and what role is played in this relationship by leptin production. The authors attempted to assemble in their small study data on leptin production in bone marrow and at the same time parameters of lipids of bone marrow which can be assessed by cytological examination. The authors examined 16 patients (9 men and 7 women) subjected to orthopaedic surgery. They assessed leptin concentrations in sera obtained from peripheral blood and bone marrow, and at the same time they assessed by morphological examination in smears of bone marrow some parameters associated with lipids. The authors found that serum leptin levels from bone marrow are significantly lower than in peripheral blood (p < 0.0005). These values correlate closely (r = +0.77, p < 0.0005). The authors found also a positive correlation between serum leptin (r = +0.56, p < 0.02) and bone marrow leptin (r = +0.72, p < 0.002) and the body mass index (BMI). A positive correlation was found also between serum (r = +0.65, p < 0.006) and bone marrow leptin (r = +0.80, p < 0.0002) and age. The authors did not detect any significant correlations between parameters of the lipids of bone marrow and leptin levels in serum and bone marrow. The assembled results can in combination with data from the literature indicate that the actual amount of leptin in bone marrow is influenced rather by its consumption by haematopoietic tissue than by its production.

[Treatment with interferon and autoimmunity]. / Lécba interferonem a autoimunita.

Interferons are commonly used, frequently already as a standard drug, in a relatively wide spectrum of indications in tumourous and non-tumourous diseases. The numerous undesirable therapeutic effects include also relatively frequent induction of autoimmune processes which, however, only rarely is associated with marked clinical manifestations. The author presents an account on two patients from their own clinical practice treated with interferon alpha who developed complications which in the author's opinion may be associated with autoimmunity (a patient with thrombocytopenia responding well to immunosuppressive treatment, originally treated on a chi ount of renal carcinoma, and a female patient with pulmonary sarcoidosis treated for essential thrombocythemia). The authors present also a brief review of the literature on autoimmunity induced by interferon.

Osteoblasts and osteoclasts in bone marrow smears of cancer patients.

Osteoblasts and osteoclasts are the unique cells occurring in bone marrow smears in situations with high bone metabolic turnover (children, trauma, rachitis, Paget disease or tumors). The collection of 2706 sternal or iliac crest aspirates from patients with hematologic malignancies and solid tumors are presented. We demonstrated significantly higher positivity for osteoblasts-osteoclasts presentation in bone marrow smears for hematological malignancies (p < 0.05), solid tumors (p < 0.01), and especially breast cancer (p < 0.001). We found a significant association between osteoblast-osteoclast positivity and dissemination of breast cancer (p < 0.05). None of the breast cancer patients without signs of dissemination (X-ray, sonography or scintigraphy) had positivity for osteoblasts or osteoclasts. We suppose that the osteoblast-osteoclast positivity in bone marrow smears can serve as a cheap marker for breast cancer dissemination.

[Agrobacterium tumefaciens (Radiobacter) as an infectious agent in an oncological patient]. / Agrobacterium tumefaciens (radiobacter) jako infekcní agens u onkologického pacienta.

The authors submit the description of a 62-year-old patient with multiple myeloma where the causal agent of pyretic reactions was Agrobacterium tumefaciens (radiobacter). It was a patient with an implanted venous port which was colonized by the above bacterium. This finding most probably has not been described so far in the Czech literature. In the English literature the authors found 36 cases. The authors draw attention to the possible higher incidence of future infections caused by organisms hitherto considered non-pathogenic for man, in particular in immunocompromised patients.

[Chemotherapy of resistant and recurrent lymphoma based on a combination of ifosfamide and etoposide. Antitumor effects, toxicity and stimulation of peripheral stem cells]. / Chemoterapie rezistentních a relabujících lymfomu zalozená na kombinaci ifosfamidu a etopozidu. Protinádorový efekt, toxicita a stimulace periferních kmenových bunek.

BACKGROUND: Treatment of Hodgkin's disease (HD) and non-Hodgkin lymphomas (NHL) is still unsatisfactory in patients resistant to primary therapy or those with early relapses. The objective of the trial was to test whether salvage regimens based on a combination of iphosphamide and etopozide have a sufficient anti-lymphoma effect, while the toxicity is still acceptable, and in conjunction with growth factors as satisfactory mobilizing potential for the collection of peripheral stem cells (PBSC). METHODS AND RESULTS: A group of 40 patients with relapsing and/or primary therapy resisting lymphomas (14 NHL, 26 HD) were treated by life saving or stimulating chemotherapy VIM (etopozide, iphosphamide, methotrexate) and MINE (iphosphamide mitoxanthrone, etopozide; mostly NHL). If the response to these regimes was inadequate, to some patients in addition mini (dexa) regimes were administered, BEAM and DHAP resp., with the objective to achieve maximum reduction of the tumourous mass before high-dosage treatment with the support of autologous PBSC. The authors administered 119 cycles of salvage chemotherapy (51 VIM, 46 MINE, 22 mini-dexa-BEAM and DHAP). The toxicity of chemotherapy and the therapeutic response were evaluated according to WHO criteria. The toxicity of VIM and MINE, with the exception for mobilization of desirable transient leukopenia, was not serious. During stimulation of PBSC on average three leukophereses were made and on average 9.9. 10(6) CD34+ cells/kg body weight of the patient were obtained and 53.2. 10(4) CFU-GM/kg (VIM), and 13.5. 10(6) CD34+ cells/kg 53.4. 10(4) CFU-GM/kg (MINE) resp. A total of 64% (MINE) and 61% (VIM) therapeutic responses were obtained, 14% (MINE) and 26% (VIM) complete remissions and 50% (MINE) and 35% (VIM) partial remissions. CONCLUSIONS: Life saving regimes, VIM and MINE, have a good antilymphoma activity, low toxicity and in combination with growth factors (filgrastim) they ensure a good collection of PBSC. As compared with other regimens, in particular for stimulation, VIM and MINE appear to be better.

[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group]. / Lécba mnohocetného myelomu vysokodávkovanou chemoterapií s transplantací autologních kmenových hemopoetických bunek a následující udrzovací lécbou interferonem alfa-2b nebo interferonem alfa-2b a dexametazonem. Zpráva o probíhající studii "4w" Ceské myelomové skupiny.

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

[Gaucher's disease in a 22-year-old female patient]. / Gaucherova choroba u 22leté pacientky.

Gaucher's disease is a sphingolipidosis with a genetically conditioned deficiency of cerebroside-beta-glucosidase which can be encountered in everyday practice and not only in paediatrics. The authors submit the case-history of a 22-year-old Ukrainian patient with a fully developed type 1 Gaucher disease, and a brief review of the diagnostic and therapeutic possibilities. Due to the more extensive migration of the population on the territory of the Czech Republic a more frequent occurrence of the disease can be envisaged.

[Treatment of chronic lymphatic leukemia]. / Lécba chronické lymfatické leukémie.

Chronic lymphocytic leukemia (CLL) is a slow lymphoproliferative disease. The therapy has only a palliative effect and therefore the common attitude to the therapy is conservative (watch and wait policy). Monotherapy with alkylating cytostatics, usually chlorambucil, is considered by most authors to be the therapy of first choice. Only the French study showed superiority of polychemotherapy CHOP over monotherapy. New drugs for the treatment of chronic lymphocytic leukemia are purine-analogs. Fludarabine has been used mostly of this purine-analogs. The response rate to fludarabine therapy is 30-45% in pretreated patients and the response rate in the chemotherapy-naive patients is about 80%. 2-chlorodeoxyadenosine was used in the same indications and it showed that this drug had a similar effect in this disease as fludarabine. The contemporary indication for fludarabine is standard-chemotherapy-refractory disease. Whether this drug will be used for initial therapy, is a question. Interferon alpha is therapeutically active in early stages of chronic lymphocytic leukemia, but it is unclear, if this response has any influence on survival. Interferon alpha is ineffective in advanced stages of this disease. The role of interferon alpha as the maintenance treatment after chemotherapy is heavily discussed.

[The effect of clodronate on bone density in patients with multiple myeloma--a 2-year follow-up of therapeutic effects]. / Vliv clodronátu na kostní denzitu pacientu s mnohocetným myelomem--dvouleté sledování lécebného úcinku.

Biphosphonates are used for the treatment of hypercalcaemia as well as in normocalcaemic patients for the long-term inhibition of malignant osteolytic bone processes. In patients with multiple myelomas treated with biphosphonates in randomized studies a reduction of the number of new osteolytic foci was proved and improvement of the quality of life. The objective of the present study was to evaluate the effect of clodronat on the development of bone density in patients with multiple myeloma. In the study since 1993 27 patients were included. In August 1995 22 patients were evaluated who were treated for more than 12 months with clodronat (Bonefos Leiras). The patients were given clodronat in i.v. infusions (five infusions à 600 mg) in three-month intervals. After six-month intervals the amount of hydroxyapatite in the lumbar vertebrae was evaluated by CT densitometry. Statistical testing of trends of assessed bone density values revealed that not even after two years of the disease a statistically significant reduction of the bone density occurs. Treatment was very well tolerated, gastrointestinal problems were an exception. At the onset of the investigation three patients had symptoms of mild tetany, and a decline of the calcaemia below normal values was recorded. As soon as regular administration of calcium preparations was started during clodronat administration, the calcaemia did not decline below normal levels and enhanced neuromuscular irritability did not develop. Clodronat stabilizes the amount of bone mass, reduces pain and also improves the quality of the patients life. It should be included among standard treatment of patients with multiple myeloma.

[Evaluation of treatment of anemia with erythropoietin in patients with multiple myeloma]. / Hodnocení lécby anémie erytropoetinem u pacientu s mnohocetným myelomem.

Multiple myeloma is very frequently associated with anaemia which has the character of hypo-proliferative anaemia of chronic diseases. In this type of anaemia the erythropoietin formation is frequently inadequate. According to data in the literature pharmacological doses of erythropoietin lead to an increase of the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was administered to 11 patients whose haemoglobin concentration was lower than 100 g/l. The results from 10 patients were finally evaluated. During the first month all patients were given erythropoietin - 150 U/kg three times per week. Unless during the first month of treatment the haemoglobin concentration increased by 10 g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value had risen above 120 g/l, the authors assessed an individual maintenance dose. In case three-month erythropoietin treatment did not lead to an increase of haemoglobin by 20 g/l as compared with the baseline value, erythropoietin administration was discontinued. The haemoglobin concentration increased by 20 g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where the haemoglobin concentration increased by 20 g/l during the first month, the endogenous erythropoietin concentration was less than 60 U/l. In another three patients the mentioned therapeutic response was recorded only during the 2nd or 3rd month of treatment after the erythropoietin dose had been increased. These three patients had higher baseline concentrations of endogenous erythropoietin, 100 to 350 U/l. During treatment no undesirable effects of erythropoietin were observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis of multiple myeloma. According to the results of the authors work and data in the literature it is obvious that in patients with endogenous serum erythropoietin below 100 U/l a rapid riae of haemoglobin can be observed already during the first month. Patients with a higher baseline concentration of endogenous erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger doses of erythropoietin must be administered. In patients with an erythropoietin value above 500 U/l there is a minimal probability that a response will be produced.

[Tolerance and results of treatment of Hodgkin's disease]. / Tolerance a výsledky lécby Hodgkinovy choroby.

At present the accepted standard chemotherapeutic treatment of Hodgkin's disease is therapy according to the MOPP pattern (mustargen, vincristine, procarbazine and prednisone) alternating with the ABVD therapeutic pattern (adriamycin, bleomycin, vinblastine and dacarbazine). It is substantial for achieving optimal results to administer the planned treatment in non-reduced doses and at the scheduled time. In the submitted paper the authors describe the tolerance of chemotherapy and its results in 15 patients and the tolerance of radiotherapy in another four patients suffering from Hodgkin's disease. Complications of chemotherapy (leukopenia and infection) caused an overall average retardation of chemotherapy of 37 days per patient. This interval would be certainly longer if the patients were not given Leucomax Schering Plough. From a total of four patients given radiotherapy Leucomax had to be administered to two, otherwise radiotherapy would have had to be discontinued on account of a decline of leucocytes.

Therapy of anemia in patients with multiple myeloma.

Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.

[Increased bone density in patients with multiple myeloma treated with clodronate]. / Vzestup kostní denzity u nemocných s mnohocetným myelomem lécených clodronátem.

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.

[Difficulties in the therapy of primary amyloidosis]. / Obtízná lécba primární amyloidózy.

The therapy of primary amyloidosis is still unsatisfactory. The response rate after the cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinaemia, brought us to the idea to test interferon alpha in the therapy of primary amyloidosis. Interferon alpha-2b was administered to the patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) daily for the treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

[Lower cardiotoxicity of adriamycin during continuous administration in patients with refractory multiple myeloma treated with cyclophosphamide, vincristine, adriamycin and dexamethasone (C-VAD)]. / Nizsí kardiotoxicita adriamycinu pri kontinuálním podání u nemocných s refrakterním mnohocetným myelomem lécených cyklofosfamidem, vincristinem, adriamycinem a dexamethazonem (C-VAD).

Standard treatment of refractory myeloma is combined VAD treatment (vincristine, adriamycin and dexamethasone). In recent years adriamycin was sometimes replaced by mitoxanthrone which caused greater myelotoxicity. As a positive feature of the exchange of adriamycin for mitoxanthrone, authors using it, report its lower cardiotoxicity. In the literature there are, however, occasional reports on a lower cardiotoxicity of adriamycin when administered in a continuous infusion. In the submitted work the authors sought answers to two questions. 1. Is the cardiotoxicity of adriamycin administered in a continuous infusion lower than the cardiotoxicity of adriamycin administered as a bolus? 2. Is it possible to add to VAD chemotherapy cyclophosphamide without increasing the toxicity excessively? After echocardiographic evaluation of the diastolic and systolic function following a cumulative dose of 200 mg the authors observed smaller changes of the above functions in the group treated with adriamycin a in a continuous infusion (patients with multiple myeloma) than in the group with bolus therapy (patients with non-Hodgkin lymphomas and acute leukaemia). Addition of 600 mg cyclophosphamide on the 5th, 10th and 20th day to the classical VAD pattern made treatment more intensive without causing a deteriorated tolerance of this treatment.

[Lack of therapeutic effect on primary amyloidosis by interferon-alpha]. / Effektlose Therapie der primären Amyloidose mit Interferon alpha.

The therapy of primary amyloidosis is still unsatisfactory. The response rate after cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in the majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinemia, brought us to the idea to test interferon alfa in the therapy of primary amyloidosis. Interferon alpha-2b was administered to a patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) i. V. daily for a treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Treatment of refractory multiple myeloma with vincristine, adriamycin, dexamethasone, and with repeated application of cyclophosphamide (C-VAD).

The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.

[Use of the computer for the evaluation of platelet aggregation]. / Pouzití pocítace pri hodnocení agregace desticek.

The authors describe some methods of evaluation for platelet aggregation. Because the approaches are different, frequently some results of aggregation in pathological conditions differ. The authors give an account of their method of evaluation of platelet aggregation by means of a small personal computer.