Therapy of Castleman's disease with siltuximab - case report and review of literature.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is characterized by constitutional symptoms, enlarged lymph nodes and laboratory test abnormalities, which are primarily related to the overproduction of interleukin-6 (IL-6). This form (iMCD) was treated earlier with cytostatics used for lymphoma, later with bio-logic therapy as rituximab, immunodulatory drugs and proteasome inhibitors, and in the last years with an anti-IL-6 antibody, siltuximab. Siltuximab is a human-mouse chimeric immunoglobulin G1k monoclonal antibody against human IL-6 approved in the European Union for the treatment of iMCD. In view of the limited treatment options for iMCD, this case report aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. CASE: We describe a young woman with iMCD diagnosed at the age of 25 years. For first line treatment, rituximab and dexamethasone were used without any cytostatic because the patient wished to give birth to a healthy child in the future. However, the response after this first line therapy was short. In addition, after 3 years from the start of rituximab + dexamethasone therapy, it was necessary to administer treatment for the relapse of iMCD. We decided for siltuximab in this young woman, still aged < 30 years, and started administration of siltuximab in 3-week intervals. RESULTS: After administration of first two infusions of siltuximab, all inflammatory markers returned to normal value. Moreover, serum hemoglobin and albumin levels as well as C-reactive protein normalized after the first two administrations of siltuximab. The clinical response continue, siltuximab is still administered in 3-week intervals. PET/CT with fluorodeoxyglucose confirmed a very good anatomic and metabolic response to the treatment. Siltuximab demonstrated a favorable safety profile, and the prolonged treatment was well tolerated. CONCLUSION: This result is encouraging and demonstrates the potential of siltuximab as treatment of CD. As earlier published, this case confirms that significantly elevated inflammatory markers in a patient with CD predict a good response to siltuximab.

Patients benefi ts from physicians empathy and results of including of empathy development into medical training.

BACKGROUND:  The extent of empathy is an individual human property, not completely dependent on cognitive intelligence. People arise with certain genetic fundament for empathy but the ability to perceive empathically develops further during the life. There has been much discussion in the medical literature about the importance of empathy and physician communication style in medical practice. Empathy has been shown to have a very real positive eff ect on patients outcomes. The literature suggests that empathy training is warranted and should be incorporated into surgical residencies through didactics, role-playing and simulations, and apprenticeship to empathic attending role models. PURPOSE: This paper reviews empathy and its importance as it pertains to the physician-patient relationship and improving patients outcomes, and the need for increased education in empathy during medical training.

[Vitamin D during cancer treatment]. / Vitamin D pri lécbe nádorového onemocnení.

Recent knowledge on vitamin D has shown that its active form not only regulates calcium and phosphate metabolism but also has significant antimitotic and cell differentiation effects. It can inhibit proliferation, angiogenesis and metastatic potential in cancer tissue. Insufficient vitamin D plasma levels are found in 20- 60% of cancer patients at dia-gnosis. By many authors, vitamin D deficiency is associated with higher aggressivity of tumor and shorter survival of patients. Even in the absence of clinical studies showing benefit of supplementation on outcome, clear recommendations are currently available for treatment of vitamin D deficiency. Owing to the high prevalence of vitamin D insufficiency in cancer patients and significant risks of its further decrease after antitumor therapy, it should become standard of care to examine 25- hydroxyvitamin D serum levels and correct vitamin D insufficiency in cancer patients.

[Heart transplantation and the subsequent treatment of AL amyloidosis]. / Transplantace srdce a následná lécba AL-amyloidózy.

UNLABELLED: Severe damage to the heart caused by AL amyloid deposits is a contraindication of high-dose chemotherapy with autologous haematopoietic stem cell transplantation. Severe heart damage caused by AL amyloid results in frequent life-threatening complications, even during the course of the classical chemotherapy treatment and it often makes keeping to the treatment schedule impossible. Scheduling heart transplantation before the treatment of AL amyloidosis will significantly improve the patients overall condition and enable them to undergo the intensive AL amyloidosis treatment with the hope that a long-term complete remission may be achieved. CASE DESCRIPTIONS: Transplantations of heart damaged by AL amyloid deposits were conducted in three patients; two men, age 48 and 54, and one woman, age 63. In the interval of 3-6 months from the heart transplantation before the scheduled AL amyloidosis treatment was initiated, an examination of bone marrow, the concentration of monoclonal immunoglobulin and free light chains was carried out. Both men had more than 10% of plasma cells in the bone marrow after the heart transplantation and the concentrations of the λ free light chains were pathologically increased. During the first-line therapy, autologous haematopoietic stem cells were harvested from peripheral blood after mobilizaton with granulocyte growth factor (filgrastim) at the dose of 5 µg/kg twice a day. During the administration of filgrastim until the end of the haematopoietic stem cell harvest, the combined immunosuppressive treatment was reduced and a corticosteroid dose was compensatory increased. The prophylactic antiviral drug valganciclovir was discontinued during the haematopoietic stem cell harvest. High-dose chemotherapy (melphalan 100 mg/m2) with autologous haematopoietic stem cell transplantation followed. In the interval from administering melphalan until the rise in neutrophil count over 2 x 109/l, antiviral prophylaxis was discontinued again, the immunosuppressive drug doses were reduced and corticoid doses were slightly increased. High-dose chemotherapy with melphalan at the of 100 mg/m2 was tolerated without major complications and without mucositis; however, in neither of the male patients did it lead to a complete haematological remission. Consequently, the second-line therapy followed using bortezomib combined with dexamethasone and also with cyclophosphamide or doxorubicin. One of these two patients reached a complete haematological remission after the bortezomib therapy; the values of free light chains were normal, immunofixation was negative, and clonal plasma cells were absent in the bone marrow. In the case of the other patient, the bortezomib therapy only induced partial remission. In this case, the third-line therapy followed, applying a combination of lenalidomide, dexamethasone and cyclophosphamide. This therapy significantly reduced the values of free light chains; however, their ratio remained pathological. To conclude, the latter response can be described as a very good partial remission. Both men currently show no signs of disease activity and are in a good clinical condition 28 and 30 months after the heart transplantation. The third heart transplantation, due to severe heart damage by AL amyloid deposits, was conducted in a woman aged 63. An examination of this woman three months after the heart transplantation showed that the original pathological values of free light chains became normal. The woman had approx. 8% of clonal plasma cells before the heart transplantation. Three months after the heart transplantation the bone marrow contained only 3% of polyclonal plasma cells. In this case, the immunosuppressive treatment with corticosteroids after the heart transplantation probably induced a complete haematologic remission. The woman is in a complete AL amyloidosis remission seven months after the heart transplantation. CONCLUSION: It was beneficial to perform the heart transplantation first and to initiate the AL amyloidosis treatment no sooner than three months after the heart transplantation in patients with severe heart damage caused by AL amyloid deposits. If the patients are in a good clinical conditions, autologous haematopoietic stem cells can be harvested after the heart transplantation and high-dose chemotherapy can be offered to the patients. If this intensive treatment does not induce remission, it is necessary to apply additional alternative treatments.

[High dose treatments and preparatory regimens prior to haematopoietic stem cell transplantation]. / Vysokodávková lécba a prípravné rezimy pred transplantací krvetvorných bunek.

High-dose chemotherapy can be defined as utilization of cytotoxic drug doses that produce bone marrow ablation. Transfusion of autologous graft serves as rescue from otherwise fatal myelotoxicity. Immune reaction of graft versus tumor that lowers relapse rates of malignant disease becomes an important contribution of allogeneic hematopoietic stem cell transplantation. New reduced intensity conditioning regimens with lower initial cytotoxicity rely on this immune effect with the potential of additional elimination of remaining cancer cells. Decreased toxicity of these regimens enables treatment of patients with comorbidity and/or in higher age.

[Cladribine is highly effective in the treatment of Langerhans cell histiocytosis and rare histiocytic disorders of the juvenile xanthogranuloma group]. / Kladribin je velmi úcinným lékem pro lécbu histiocytózy z Langerhansových bunek a vzácných histiocytárních nemocí ze skupiny juvenilního xantogranulomu.

UNLABELLED: 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. CONCLUSIONS: 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).

[Chronic disseminated intravascular coagulation (DIC) markers in a patient with multiple angiomatosis during treatment with anti-angiogenics: interferon α, thalidomide and lenalidomide]. / Vývoj koagulacních markeru chronické diseminované intravaskulární koagulace (DIK) u pacienta s mnohocetnou angiomatózou v prubehu lécby antiangiogenními léky: interferonem α, thalidomidem a lenalidomidem.

BACKGROUND: Multiple angiomatosis is a rare disease with angiomatous formations in multiple organs and tissues and associated with a risk of fatal bleeding. CASE DESCRIPTION: In this patient, the bones, pleural and peritoneal cavities and digestive tract were involved. The patient had long-term been administered zoledronate that provided relief from bone pain as early as after the second dose. The effect of antiangiogenics was evaluated on CT and MRI. Since angiomatous proliferation is associated with chronic disseminated intravascular coagulation (DIC) and anaemisation, blood count and fibrinogen as well as D-dimer and soluble fibrin monomer concentrations are also used to assess treatment response. RESULTS: Before treatment, D-dimer levels were in excess of 20 µg/mL, fibrinogen 1.4 g/L and soluble fibrin monomers were at measurable levels. During treatment with interferon α at a dose of 6 million units 3 times a week with the dose reduction after 10 month, the median fibrinogen concentration increased to 1.5 (1.2-2.0) g/L, the median D-dimer levels declined to 17.2 (13.4-20.0) µg/mL and fibrin monomers were still detectable. Thalidomide therapy (100 mg/day) provided reduction in the median D-dimer levels to 6.07 (4.71-10.21) µg/ml and increase in median fibrinogen concentration to 1.9 g/L; soluble fibrin monomers were unidentifiable. CT imaging suggested significant reduction of angiomatous mass. Progressing neuropathy required dose reduction of thalidomide to 50 mg/day, leading to D-dimer increase. Lenalidomide 10 mg/day provided an increase in median D-dimer concentration to 10.8 (10.8-17.35) and decline in the level of haemoglobin to a median of 124 (135-117) g/L. Soluble fibrin monomers became detectable again. Therefore, a low dose of lenalidomide 10 mg/day was combined with thalidomide 100 mg and, subsequently, 50 mg/day. Treatment with lenalidomide 10 mg and thalidomide 50 mg provided median D-dimer levels of 9.32 and the disease has remained stable for 9 months. CONCLUSION: Thalidomide 100 mg/day stabilized multiple angiomatosis better than interferon alfa. Thalidomide 50 mg/day was insufficient to maintain disease stability. Lenalidomide at a dose of 10 mg was tolerated really well but this dose was insufficient to maintain low D-dimer levels and normal haemoglobin concentrations. The combination of lenalidomide 10 mg and thalidomide 50 mg daily stabilized the disease for 9 months.

[Six-year follow-up of a patient with multiple angiomatosis involving skeleton, thoracic and abdominal cavities and the gut wall]. / Sestileté sledování pacienta s mnohocetnou angiomatózou postihující skelet, brisní i hrudní dutinu a stenu trávicí trubice.

BACKGROUNDS: Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage. OBSERVATION: A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia. RESULTS: Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1-21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84-141) g/l. The median of D-dimer decreased to 9.3 (8.0-17) µg/mL. CONCLUSION: Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patients disease has been stable for 9 months.

Long-term results of allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin.

UNLABELLED: Reduced-intensity conditioning (RIC) is widely used for allogeneic stem cell transplantation (SCT). Here we present our long-term experience with RIC regimen consisting of fludarabine (30 mg/m2/day on days -10 to -5), busulfan (4mg/kg/day on days -6 and -5) and antithymocyte globulin (ATG Fresenius, 10 mg/kg/day on days -4 to -1) (Flu-Bu-ATG) in a cohort of 71 patients with various hematological malignancies including chronic myeloid leukemia (24 patients), acute myeloid leukemia (19 patients), lymphoma (20 patients), multiple myeloma (3 patients), myelodysplastic syndrome (3 patients), and myelofibrosis (2 patients). The median age was 50 years. The overall response rate was 87%, including 83% CR and 4% PR. The incidence of acute and chronic GVHD was 35% and 52% and the cumulative incidence of non-relapse mortality at 1 year and 4 years was 8% and 14%. With the median follow-up of 55.0 months, the 2- and 4-year event-free survival (EFS) was 49.0% and 40.3%, and the overall survival (OS) was 73.2% and 62.6%, respectively. Gender, age at SCT, type of donor, disease status at SCT, previous autologous transplantation, and complete chimerism by day +100 did not significantly influence EFS and OS. In a multivariate analysis, no presence of chronic GVHD (p=0.029, HR: 2.5),and diagnosis other than CML (p=0.018, HR: 4.6), and CD34+ dose < 5x106/kg (p=0.010, HR: 2.8) were significant predictors of poor OS. Flu-Bu-ATG protocol is a RIC regimen that combines effective disease control with low non-relapse mortality and acceptable toxicity profile. KEYWORDS: reduced-intensity conditioning, fludarabine, busulfan, antithymocyte globulin.

[Sepsis and the septic shock in oncological or other immunocompromised patients--diagnosis, therapy]. / Sepse a septický sok u onkologicktch a imunokompromitovaných patientu--diagnostika, terapie.

Sepsis and the septic shock and the up to date knowledge about them represent a marked drifting for diagnostics and the treatment of this complications. Their application in patients with the oncological disease or the other immunocompromised patients represents further extension in the specific group of patients with several unique properties. In despite of the improving results in the oncological treatment there are only few reports in literature about this group of patients and this one is steadily growing due to the progressive improving of the supportive care in oncology. This group of patients with the febrile neutropenia and the sepsis (the most frequent complication) request the special focus of general practitioners and the internists because these ones are with these patients in contact as a first. They have to master the basal image about the specialties of this patient group. In our article we analyze this group of patients with focus on antibiotics in febrilie neutropenia and sepsis and on the other supportive care in the immunocopromised patients.

[Universities need to have high quality education as well as an effective quality control of their students' (products') knowledge and skill base]. / Vysoké skoly musí mít nejen kvalitní výuku, ale také úcinnou kontrolu kvality znalostí a schopností studentu (produktu) vysoké zkoly.

In order for the schools of medicine to produce high quality physicians, they have to provide high quality education as well as they must ensure that knowledge building is taking place in the course of the programme and that the students whose efforts and/or abilities do not allow achievement of the required criteria are eliminated. Exams used to be the standard quality control tool. However, current information technologies allow doubling-up of this control; retaining the traditional examinations but preceding them with the requirement to complete multiple-choice tests. The text summarizes our experience with examining the students' mental presence during teaching with tests and our plans for the combined form of exit control using tests, completion of which will be prerequisite to admission to the exam itself. We do not believe that tests should completely replace exams but we do believe that the requirement to pass the exam should only take place following previous successful completion ofa test. This is achievable ifwe manage to establish a computer teaching room, i.e. examination room, and transform a vast number of questions into high quality multiple choice tests.

[Histiocytosis from Langerhans cell in adults--experience of one department and review of treatment alternatives]. / Histiocytóza z Langerhansových bunek u osob dospelého veku--zkusenosti jednoho pracoviste a prehled lécebných mozností.

Thirteen patients with Langerhans cell histiocytosis (LCH) have been treated in hospital Brno Masaryk University during the last 15 years. In 4 cases of this total amount, the diagnosis was made in childhood and these young adults were referred to our department from Pediatric cancer center. In 9 cases, the diagnosis has been made in people elder than 18 years. The disease recidived in 3 patients with LCH diagnosed in childhood, in one case with neurodegenerative impairment of brain. In 4 patients from the total of 9 with LCH diagnosed in age over 18 years, the disease had aggressive course with several recidives. In one case it was pulmonal and multifocal osseal manifestation, in two cases multifocal osseal disease. Isolated pulmonal form of LCH was diagnosed only in one patient. By the first patient, high dose melphalan and etoposide with peripheral blood stem cell transplantation was performed after failure ofvincristin and prednison therapy and failure of etoposide therapy. The first remission after this high dose therapy lasted only 2.5 years. For relapse second cycle of the same high dose therapy was administered, but the next remission was much shorter. By the two patients with multifocal recidives in bones 2-chlordeoxyadenosine was administered as initial therapy. These patients are followed up for more then 24 months and they are without relapse of this disease. The 2-chlordeoxyadenosine is very efficient in multifocal bone form of LCH and has potential to reach long remission. Therefore in a case of aggressive multifocal disease we would prefer 2-chlordeoxyadenosine therapy as therapy of the first choice.

Pulse cyclophosphamide for corticosteroid-refractory graft-versus-host disease.

Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m(2) was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.

Palliative treatment of cancer anorexia with oral suspension of megestrol acetate.

Megestrol acetate (MA) is a progestational agent, currently known as one of the most effective appetite stimulants in patients suffering from cancer anorexia/cachexia syndrome. Oral suspension of this drug may be particularly useful in patients with far advanced disease, where taking larger amount of pills may lead to the decrease of patient compliance. The influence of oral MA suspension on quality of life and nutritional status was evaluated in 22 patients with far advanced cancer suffering from anorexia and more than 5 per cent weight loss, all beyond the scope of anticancer treatment. Most patients had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue scale (VAS) for appetite, anthropometry, maximal handgrip strength and laboratory data were obtained before treatment and then after 2, 4, and 8 weeks of therapy. Despite of a known high mortality in this prognostically unfavorable group of patients (36% within two months in this study), overall quality of life after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite was the most successfully influenced parameter with an improvement in VAS in 95% of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the great majority of patients. Oral suspension of megestrol acetate maybean effective palliative treatment for many patients with far advanced cancer suffering from anorexia/cachexia syndrome.

[Treatment of acute lymphoblastic leukemia in adults with seven-drug induction therapy and intensive consolidation with or without autologous stem cell transplantation followed by maintenance therapy. Experience of a single center]. / Terapie akutní lymfoblastické leukémie dospelých kombinací sedmi chemoterapeutik v indukcní lécbe, intenzivní konzolidací s autologní transplantací kmenových bunek krvetvorby nebo bez ní a s následnou udrzovací lécbou. Zkusenosti jednoho centra.

BACKGROUND: During the last few years, improvement in prognosis of the adult acute lymphoblastic leukaemia (ALL) has been modest. The probability of leukemia-free survival is 20-40%. Philadelphia-chromosome positive (BCR-ABL positive) ALL has the worse prognosis. A single centre experience with treatment of ALL in adults is reported. METHODS AND RESULTS: Between April 1997 and July 2000, 15 consecutive patients with de novo adult ALL (7 T-lineage ALL, 7 B-lineage ALL, 1 null ALL) begin their treatment with the seven-drug induction regimen (in phase I, daunorubicin, vincristine, L-asparaginase, i.v., and prednisone, p.o.; in phase II, 6-mercaptopurine, p.o., cytosine arabinoside and cyclophosphamide, i.v.) and central nervous system (CNS) prophylaxis (methotrexate and CNS irradiation in patients without total body irradiation in conditioning regimen), with intensive consolidation (three times high-dose methotrexate and high-dose-cytarabine, i.v.), and with/out autologous peripheral blood stem cell transplantation (PBSCT) followed by maintenance chemotherapy (6-mercaptopurine and methotrexate, p.o.). Seven patients received autologous PBSCT. Median patient age was 30 years. Three patients were BCR-ABL positive at diagnosis. With median follow-up 14 month (range 0.1-46 month), seven (4 T-lineage ALL, 2 B-lineage ALL, 1 null ALL) out of 15 patients are alive in remission (four of them receiving autologous PBSCT). Causes of death were relapse (n = 3), chemotherapy related toxicity (n = 2), infection (n = 1), and acute myeloid leukaemia developed 10 months after autologous PBSCT (n = 1). All BCR-ABL positive patients died. CONCLUSIONS: Chemotherapy alone and autologous PBSCT with maintenance therapy may be curative for adult patients with ALL. We can recommend these treatment options for patients without risk factors in particular.

Bone mineral density in multiple myeloma patients after intravenous clodronate therapy.

Bisphosphonates inhibit osteoclastic bone destruction that may be stimulated by myeloma cells. By this way, bisphosphonates carry the potential to lower the number of new pathological fractures, of hypercalcaemic events, and of intensity of bone pain as was published earlier. Clodronate has been administered orally in most clinical studies so far despite of its poor bioavailability from the gastrointestinal tract. The aim of our study was to evaluate bone mineral density (BMD) changes in 34 newly diagnosed multiple myeloma patients regularly treated by 900 mg of clodronate in slow intravenous infusions on an outpatient basis in two-week intervals for at least 24 months. BMD was evaluated by CT scanning every six months. Initial values of trabecular BMD were only about 60 per cent of age- and sex-adjusted healthy population values. Clodronate therapy seemed to preserve BMD within the period of two or three years. This effect was seen not only in patients responding to chemotherapy but even in the small subgroup of patients with persisting active disease. We conclude that the long-term intravenous clodronate therapy may contribute to the preservation of BMD and thus calcium hydroxyapatite in bones in multiple myeloma patients concomitantly treated by chemotherapy. The administration of clodronate should start early in the course of disease, before BMD has been markedly reduced.

[High-dosage chemotherapy with support of autologous haematopoietic cells in the treatment of multiple myeloma--review of contemporary possibilities]. / Vysokodávkovaná chemoterapie s podporou autologních hemopoetických bunek v terapii mnohocetného myelomu--prehled soucasných mozností.

High-dosage chemotherapy with autologous transplantation of haematopietic stem cells prolonged the survival of patients with multiple myeloma as compared with results of standard chemotherapy, on average by 1.5 years. Nowadays this method is the standard treatment for suitable patients. Findings assembled recently are discussed by the authors.

[Treatment of AL-amyloidosis and some other types of amyloidosis]. / Lécba AL-amyloidózy a nekterých dalsích typu amyloidóz.

Patients with AL-amyloidosis are treated at present by conventional or large-dose chemotherapy with autologous transplantation of haematopoietic stem cells, similarly as patients with multiple myeloma. Only the timing of treatment is different. In myeloma treatment is usually indicated only in clinical stage II or III, in clinical stage I only in case of adverse prognostic factors. In AL-amyloidosis treatment is indicated immediatelyafter establishment of the diagnosis. It was found that high-dose chemotherapy with autologous transpantation of haematopoietic cells is at present the most effective treatment for selected patients with not advanced forms of primary systemic AL-amyloidosis. Allogenic transplantation of the liver is treatment of choice in ATTR amyloidosis. In AA-amyloidosis the basis of treatment is removal or suppression of the chronic inflammatory process, possibly colchicin administration.

[Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease]. / Efekt vysokodávkované chemoterapie u nemocných s relabující nebo rezistentní Hodgkinovou chorobou.

The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.

[Monoclonal gammapathy of undetermined significance (benign monoclonal gammapathy)]. / Monoklonální gamapatie nejasného významu (benigní monoklonální gamapatie).

Monoclonal gammapathy is a condition that may be related to the malignant lymphoproliferative disease, but more often to a benign lymphoproliferation. Formerly termed benign monoclonal gammapathy it is now called monoclonal gammapathy of unknown significance (MGUS), because years later malignant lymphoproliferative disease may develop. Even benign gammapathy may cause frequent symptoms in a patient. The text describes clinical manifestations of monoclonal protein including various differential diagnostic possibilities.