[Monoclonal Antibodies in the Treatment of Chronic Lymphocytic Leukemia in 2015]. / Monoklonální protilátky v lécbe chronické lymfocytární leukemie v roce 2015.

Chemotherapy combinations with monoclonal antibodies are now the basis for treatment of chronic lymphocytic leukemia. Rituximab, the most widely used anti-CD20 antibody in routine clinical practice, led not only to improvement of progression-free survival, but also to improvement of overall survival in previously untreated patients with good performance status in combination with fludarabine and cyclophosphamide. This regimen has become the standard treatment for patients in good physical condition. Rituximab and the newest anti-CD20 antibody obinutuzumab in combination with chlorambucil, as compared with chlorambucil alone, prolonged overall survival in previously untreated patients with significant comorbidities, and the combination of anti-CD20 antibody with chlorambucil has become the standard regimen in this group of patients. Alemtuzumab and ofatumumab improved treatment results in refractory chronic lymphocytic leukemia. Targeted therapy with combination chemotherapy and monoclonal antibody in patients with chronic lymphocytic leukemia represents a significant advance in the treatment of this disease.

[Advances in the treatment of chronic lymphocytic leukaemia]. / Pokroky v lécbe chronické lymfocytární leukemie.

Chronic lymphocytic leukemia (CLL) is the most common forms of leukemia in the western world and is characterized by a highly variable clinical course. Some patients live for many years without treatment, whereas other have disease with rapid progression. The treatment of chronic lymphocytic leukemia has achieved extraordinary progress over the last years with the incorporation of monoclonal antibodies and combined chemoimmunotherapy. Despite these therapeutic successes, CLL is still considered to be an incurable disease. Only the allogenic transplantation is potentially curative but it is feasible only for selected group of younger patients without comorbidities. However, elderly and comorbid patients, who represent the majority of CLL population, are not usually able to undergo intensive treatment. The search for new treatment options is therefore still relevant. This review summerizes the current treatment options and newly tested drugs in CLL.

[Guidelines for alemtuzumab treatment in chronic lymphocytic leukaemia (CLL)]. / Doporucení pro lécbu alemtuzumabem u chronické lymfocytární leukemie (CLL).

UNLABELLED: Alemtuzumab, the humanized monoclonal anti-CD52 antibody, is an effective agent in the treatment of fludarabine-refractory chronic lymphocytic leukemia (CLL). Due to many specific issues associated with alemtuzumab treatment, the Working Committee of Czech CLL Study Group developed these guidelines. SUMMARY OF RECOMMENDATIONS: (1) The main indication of alemtuzumab is fludarabine-refractory CLL. (2) Further possible indications include first-line treatment (in patients who cannot be treated by fludarabine-containing regimens), therapy of patients with del 17p, treatment of refractory autoimmune cytopenias and management of patients with severe cytopenias due to bone marrow infiltration. (3) The treatment should last 12 weeks and should not be terminated prematurely if there are no signs of CLL progression; bone marrow aspirate/biopsy can be performed after 12 weeks of treatment. (4) Subcutaneous administration of alemtuzumab seems to be equally effective with advantageous reduction of infusion-related adverse events. (5) Patients treated with alemtuzumab must receive combined antimicrobial prophylaxis against Pneumocystis jiroveci and herpetic viruses. Cytomegalovirus viremia should be monitored using weekly PCR from peripheral blood. (6) Use of alemtuzumab in combinations and consolidation/maintenance protocols must be considered experimental and needs optimization within prospective clinical trials. (7) Alemtuzumab treatment should be conducted by an experienced hematologist within a center of intensive hematology care.

[Burkitt lymphoma in pregnancy--case report]. / Burkittuv lymfom v tehotenství--kazuistika.

OBJECTIVE: The aim of the study is to show the possible variations of early symptoms of haematological malignity during pregnancy and to summarize data about treatment modalities and possible management of gravidity in case of the disease. DESIGN: Case report. SETTING: Department of Obstetrics and gynaecology, Charles University, 2nd Medical Faculty; 1st internal clinic - department of hematology, Charles University, 1st Medical Faculty, Prague. METHODS: Pubmed database was searched between years 1989 and 2009. The data we used focused on non- Hodgkin's lymphomas diagnosed during pregnancy, especially on Burkitt lymphoma. The treatment modalities, neonate outcomes and prognosis of the mothers were emphasised. CONCLUSION: The diagnostics of haematological malignities in pregnancy is difficult. The most frequent symptoms are subfebris, fever of unknown etiology, lymphadenopathy, night sweats, infirmity and the weight lost. According to the literature the Burkitt lymphoma is potencialy currable disease during pregnancy. The close cooperation of the gynecologists and hematooncologists and the individualization of treatment based on the stage of pregnancy, localization of the tumorous mass and the agresivity of disease is needed.

Positron emission tomography at the end of first-line therapy and during follow-up in patients with Hodgkin lymphoma: a retrospective study.

BACKGROUND: Routine positron emission tomography (PET) in follow-up of Hodgkin lymphoma (HL) after treatment is still controversial. The aim of this retrospective study was to analyze the clinical impact of routine PET examination during the follow-up for relapse detection in PET-negative HL patients at the end of therapy. PATIENTS AND METHODS: PET scans were carried out in 113 HL patients at the end of therapy and during the follow-up either in regular intervals or in a suspected relapse. Median follow-up of the group was 34 months. RESULTS: Overall 327 PET scans were evaluated in 113 patients (median three PET scans per patient). At the end of therapy, 94 (83.2%) patients were PET negative and 19 (16.8%) PET positive. Regular follow-up PET scans in 67 of 94 PET-negative patients correctly identified tumor in 6 of 155 PET scans (3.9%). In 27 of 94 patients with clinically suspected relapse, 5 of 27 PET scans (18.5%) confirmed tumor. CONCLUSIONS: Our analysis showed that there is no need for regular follow-up with PET scans in PET-negative patients at the end of therapy: the ratio of true-positive PET scans during the follow-up is low (3.9%). Positive PET at the end of therapy and during follow-up should be evaluated with caution.

Dendritic cells and T lymphocyte interactions in patients with lymphoid malignancies.

Dendritic cell (DC) vaccination is an attractive approach to the treatment of patients with lymphoid tumors. To evaluate its feasibility, we have tested the functional properties of DC and T-lymphocytes in patients with treated and untreated chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). Healthy volunteers were used both as controls and as a source of cells for allogeneic mixed leukocyte reaction (MLR). In these reactions, dendritic cells from both untreated and treated patients were comparable to dendritic cells from healthy volunteers. In all the untreated patients studied, autologous dendritic cells promoted the survival and proliferation of both CD4 and CD8 lymphocytes (though the proliferation response was much better in the CD4 subset), whereas only 3 out of 5 treated patients were able to mount this response with CD4 lymphocytes and 4 out of 5 with CD8 lymphocytes. In 3 out of 5 untreated patients, pulsing of DCs with tetanus toxoid promoted a better CD4 response than was achieved with unpulsed DCs, while none of 5 treated patients had an additional response after pulsing with tetanus toxoid. None of patients studied, either treated or untreated, had a better CD8 response to pulsed DCs than to unpulsed ones. During CD4 lymphocyte proliferation, more CD4(+)CD25(hi) lymphocytes were generated in both treated and untreated patients than in healthy controls. Poor proliferation of cytotoxic cells and preferential proliferation of CD4(+)CD25(hi) T-regulatory cells in response to self and/or foreign antigens might be one of the mechanisms responsible for immunosuppression and impaired tumor surveillance in patients with lymphoid malignancies.

[Flow cytometric differential gating strategy for evaluation of T-lymphocyte survival and proliferation in mixed lymphocyte reaction with dendritic cells]. / Hodnocení prezití a proliferace T-lymfocytu ve smísené lymfocytární reakci s dendritickými bunkami metodou diferenciálního gatingu.

Mixed lymphocyte reaction (MLC) of T-lymphocytes with dendritic cells is one of the basic tools for studying of immune reaction mechanisms. This work describes a new method of evaluation of allogeneic and autologous MLC by flow cytometry and differential gating. This method is based on fixed time acquisition of events and their sorting according to their forward and side scatter properties. Differential gating distinguishes populations of all living cells (R1), living non-proliferating cells (R2) and dead/apoptotic cells (R4). Addition of fluorescence microspheres (R3) enables the calculation of absolute number of cells in a given sample volume. Using the method of 7-AAD positive cells project into the exclusion, we have shown that approximately 90% of 7-AAD R4 gate. Moreover, there was an excellent correlation between the R1: R2 ratio and the percentage of cells positive for activation/proliferation marker CD71. The method of differential gating in its basic version does not require use of any fluorescent antibody and therefore is suitable for rapid screening of large number of samples at reasonable cost and without the use of radiolabeled nucleotides.