[News in the Supportive Care of Chronic Lymphocytic Leukemia]. / Aktuality v podpurné lécbe chronické lymfocytární leukemie.

Patients with chronic lymphocytic leukemia have disrupted cellular and humoral immunity with quantitative and qualitative impairment of the cells of the immune system. Immunity disbalance leads to increased incidence of infections and autoimmune cytopenias. Supportive care for chronic lymphocytic leukemia focuses on prevention and treatment of these complications and consists of antimicrobial prophylaxis, substitution of immunoglobulins, immunosuppressive therapy, growth factors and blood transfusions.

[Lenalidomide induced therapeutic response in a patient with aggressive multi-system Langerhans cell histiocytosis resistant to 2-chloro-deoxyadenosine and early relapsing after high-dose BEAM chemotherapy with autologous peripheral blood stem cell transplantation]. / Lenalidomid indukoval lécebnou odpoved u pacienta s agresivní multisystémovou formou histiocytózy z Langerhansových bunek (LCH), rezistentní ke 2-chlorodeoxyadenosinu a casne relabující po vysokodávkované chemoterapii BEAM s autologní transplantací kmenových hemopoetických bunek.

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.

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.

[Staging of non-Hodgkin's lymphoma--recommendations of the Czech Lymphoma Study Group]. / Urcování rozsahu onemocnení u non-Hodgkinových lymfomu--doporucení Kooperativní lymfomové skupiny.

BACKGROUNDS: The Ann Arbor system is typically used for the staging of Non-Hodgkin's lymphomas. This classification was nevertheless originally developed in the 1970s for Hodgkin's lymphoma, a disease usually confined to the lymph nodes with less frequent dissemination to extralymphatic organs/tissues and extremely rare primary extranodal involvement. Non-Hodgkin's lymphomas, however, are more often associated with extralymphatic involvement and primary extranodal lymphomas are relatively common (approximately 1/3 of cases). Therefore, the value of the Ann Arbor staging system appears to be limited in these cases. An analysis of data from centres participating within the Czech Lymphoma Study Group showed that staging of Non-Hodgkin's lymphomas with extranodal involvement is not uniform. DESIGN: At the end of 2009, a draft for a Non-Hodgkin's lymphomas staging system was put forward for use by the lymphoma register of the Czech Lymphoma Study Group with special regard paid to the involvement of extralymphatic organs/tissues. This draft was further refined following comments from members of the Czech Lymphoma Study Group committee and the final form was accepted at the meeting of the Czech Lymphoma Study Group committee in January 2010. RESULTS: A consensus was reached at the meeting of the Czech Lymphoma Study Group committee regarding the staging of various combinations of nodal and extranodal involvement. For the purpose of suitable staging and appropriate treatment intensity, extranodal organs were divided into "major"--liver, lungs, bones, mesothelium (pleura, peritoneum, pericardium) and soft tissues. All other organs were defined as "minor". CONCLUSION: The Ann Arbor staging system is suitable for the staging of Non-Hodgkin's lymphomas with lymph node/lymphatic tissue involvement. As regards the extralymphatic spread of the disease or primary extranodal lymphomas, this classification should rather be adapted to practical needs. The validity of the updated classification system will be assessed in both prospective and retrospective Czech Lymphoma Study Group studies.

[Alemtuzumab in chronic lymphocytic leukemia treatment: retrospective analysis of outcome according to cytogenetics]. / Alemtuzumab v terapii chronické lymfocytárni leukemie: retrospektivní analýza a hodnoceni lécebné odpovidi podle cytogenetickiho rizika.

UNLABELLED: Alemtuzumab in chronic lymphocytic leukemia treatment: retrospective analysis of outcome according to cytogenetics SUMMARY: Alemtuzumab is effective in B-cell chronic lymphocytic leukemia (CLL) with 17p deletion, which responds poorly to chemotherapeutic agents. Our retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced CLL, categorized by cytogenetic profile. Data were collected from 74 consecutive who had received alemtuzumab. Median of previous therapies was 2. The incidence of cytogenetic abnormalities was: trisomy 12, 10%; 13q deletion, 13%; 11q deletion 25%; 17p deletion, 26%; none of these, 26%. The overall response rate was 65% (11% complete remission, 54% partial remission) in the whole cohort. From start of alemtuzumab therapy, median progression-free survival was 217 days, median time to alternative treatment was 287 days, and median overall survival was 999 days in the total cohort, respectively. Alemtuzumab was effective across all cytogenetic categories evaluated. There were no statistically significant differences between subgroups in the level of efficacy.

[Preparation of patients on anticoagulant treatment for invasive surgery]. / Príprava patientu s antikoagulacni lébou k invazivním zákrokum.

The management of warfarin therapy in patients undergoing surgery or other invasive procedures involves a balance between the risk of hemorrhage, and the risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of procedure and on pre-existing conditions. Procedures with low risk of hemorrhage (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need stop warfarin and start bridging anticoagulant therapy, such as unfractionated heparin or low molecular weight heparin, prior and after surgery. In patients requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh frozen plasma can be used to improve coagulation.

[Bleeding complications of anticoagulant therapy]. / Krvácivé komplikace antikoagulacní lécby.

Anticoagulant therapy is one of the most common forms of medical intervention. It is the mainstay of prevention and treatment of thrombotic events. Omission of adequate anticoagulant prophylaxis at least for moderate-risk and high-risk patients is a widely recognized medical error. Bleeding is one of the most feared complications of anticoagulant therapy, and is a risk of all anticoagulants. Whereas unfractionated heparin and warfarin, the oldest and most widely used anticoagulants, have specific antidotes for their anticoagulant effect, many of the newer agents (direct and indirect inhibitors of coagulation factors Xa and/or IIa) do not have specific antidotes to reverse their actions. The use of novel anticoagulants is further complicated by a lack of easily available laboratory tests to measure their levels and thereby optimize their benefit and safety in clinical practice. In this review, we evaluate the risk of bleeding associated with current anticoagulants, review the data available on current and experimental agents used for the reversal of anticoagulation, and provide recommendations for the management of major bleeding associated with anticoagulant therapy and for the management of asymptomatic overdosing of the anticoagulants.

[Molecular genetic characterization of chronic lymphocytic leukemia aggressivity in Czech patients: a nucleotide variability of genes coding for heavy chain of immunoglobulin]. / Molekulárne -genetická charakterizace agresivity chronické lymfocytárni leukémie u ceských pacientu: nukleotidová variabilita genu kódujících syntézu tezkého retezce imunoglobulinu.

BACKGROUND: Chronic lymphocytic leukemia is a heterogeneous disease manifesting with a variable clinical course. It is evident from many studies, that the division into two main prognostic categories is possible on the basis of mutation status of the immunoglobulin heavy-chain gene. The objective of our work was to identify a presence or absence of IgVH gene mutations in B-CLL patients which are monitored or treated on hematological clinics and to determine the presence of individual D and J, subgenes in malignant population of B-cells. METHODS AND RESULTS: A nucleotide sequence of IgVH gene of neoplastic cells was analyzed by appropriate molecular-genetic methods. RNA/cDNA was collected from 358 patients and a spectrum of individual subgenes translocations was identified. Our results show that 56.3% of patients manifested an unmutated variable (VH) segment. It is expected from the published data that this group of patients will suffer from aggressive course of the disease and will exhibit a substantially shorter survival in comparison to patients possessing somatic hypermutations. An expanded population of leukemic B-cells showed increased occurrence of clones whose variable segments belong to three different families. VH3 alleles are the ones most frequently used. A frequency of unmutated alleles is prominently shifted into families with V I homology. The preferred "diversity and joining" segments are D3, D2 and JH 4 and JH 6. CONCLUSIONS: The analysis of heavy chain immunoglobulin gene after recombinant VH-D-J11 segments translocation belongs to a standard hematooncological investigation. The results are an important prognostic criterion for prediction of expected disease aggressivity and for a minimal residual disease monitoring.

[Prevention of venous thromboembolism: generally accepted guidelines]. / Prevence zilní tromboembolické nemoci: obecne platná pravidla.

This article summarizes the published data on the prevention of venous thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It is recommended to sort patients according the thrombosis risk and to make use of the standard prophylactic modes. In low risk patients, no specific thromboprophylaxis is needed. Patients with moderate risk levels are candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression. At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people after major orthopaedic surgeries and with a history of heparin induced thrombocytopenia over the past three months. An alternative to the administration of LMWH even after the end of the hospitalization can be warfarin in certain situations. The sole use of acetylsalicylic acid or Rheodextran is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis.

[Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology]. / Prevence zilní tromboembolické nemoci v chirurgii, v laparoskopické chirurgii, v cévní chirurgii a v urologii.

The article summarizes published data regarding the prophylaxis of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology. In surgical patients with low risk, no specific thromboprophylaxis is needed. Patients with moderate risk levels are the candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3 400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression (IPC). At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration (LDUH) over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people with a history of heparin induced thrombocytopenia over the past three months. The sole use of acetylsalycilic acid is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC is indicated only in those patients who undergo laparoscopic surgeries and who moreover display the additional thrombosis factors. Patients with additional risk thrombosis factors undergoing major venous reconstructions require prophylaxis with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low risk urologic surgery require no specific thromboprophylaxis. If they undergo a major intervention and/or they display additional risk thrombosis factors, they require the administration of LMWH or LDUH. Elastic panty-hose and/or intermittent pneumatic compression have the same indication as in abdominal surgeries.

[Hemorrhagic complications during warfarin treatment]. / Krvácivé komplikace pri lécbe warfarinem.

Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice.

[Heparin induced thrombocytopenia]. / Heparinem indukovaná trombocytopenie.

This article describes the pathogenesis, diagnostics, treatment and prevention of heparin induced thrombocytopenia (HIT). Although HIT is considered to be a hematological diagnosis, every physician who treats patients with heparin can encounter it in daily practice. It is even more probable that surgeons of any specialisation will meet with HIT patients. A section of them elude diagnostic detection. There are two forms of HIT - HIT I and HIT II. HIT I is caused by a direct pro-aggregation effect of heparin. It has no clinic significance. HIT II is an antidote mediated adverse reaction to heparin. Antidotes will generate only after the exposure to heparin. They are targeted against the platelet factor 4 and they act only at the presence of heparin. They may lead to the aggregation of thrombocytes in the vascular system (there is a decrease in thrombocyte count). This event can be accompanied by a development of venous or arterial thrombosis that can have a rapid and even fatal course. This fact clarifies the importance of HIT II diagnostics. Diagnosis of HIT II is based on recognizing of the typical decrease in thrombocyte count usually 1 day after heparin administration is initiated. Clinical manifestations are more likely in patients with already damaged endothelium. If thrombocyte count decrease is not connected with clinical manifestations, it is the so called isolated HIT II and in patients who display the signs of thrombosis, it is HIT II associated with thrombosis. The goal of this article is apart from implementing the recommendations of the 7th conference of the American Respiratory Society in real life also the exploration of the diagnostic and therapeutic limits (availability) in the Czech Republic.

Craniofacial morphology in unilateral cleft lip and palate in adults.

X-ray measurements were used for studies of craniofacial morphology in unilateral (right-sided) cleft lip and palate in 58 adult males operated upon with the same technique. The results obtained showed a slightly smaller neurocranium without marked changes of the cranial base. Basic facial skeletal deviations included a shortening of maxillary depth, reduction of the upper face height, widening of some maxillary dimensions (interorbital and of nasal cavity), retroinclination of upper incisors and alveolar process and mandibular changes resulting from growth deficiency (they consisted of shortening of the body and ramus, elongation of anterior mandibular height, obtuse gonial angle, acute chin angle, steeper slope of the body, retroinclination of incisors and retrognathia). Described changes caused an impairment of sagittal and vertical jaw relations, anterior crossbite, flattening of the face and a limitation of its anterior growth rotation. There was also a displacement of the whole maxilla backwards and a reduction of the height and of the thickness of the upper lip (increasing retrocheilia). The elongation of the lower face and thus of the whole face was produced by the increase of the anterior height of the mandible, impaired overjet and by maxillary dentoalveolar retroinclination. A slight transversal flattening of the face (greater retrusion in the centre than in the zygomatic regions) was present as well.

Differences in craniofacial morphology between complete and incomplete unilateral cleft lip and palate in adults.

Differences in craniofacial morphology between complete and incomplete unilateral cleft lip and palate were studied in adult males by roentgenocephalometry. Incomplete clefts did not have the widening of the nasal cavity, reduction of the upper face height, or reduced thickness of the upper lip found in complete clefts. The shortening of maxillary depth was half that noted in complete clefts. The mandibular deviations and interorbital widening did not differ. The same held true for the retroinclination of upper incisors and alveolar process and backward shift of the maxilla. These changes accounted for differences in sagittal maxillo-mandibular relations, facial profile, occlusion of incisors and total facial height between complete and incomplete clefts. Limitation of anterior growth rotation of the face was identical. The independence of mandibular variations on the extent of the cleft and on maxillary malformation suggests the possibility of an underlying primary impairment of growth of the lower jaw, at least in some cases.