Interni hematologicka a onkologicka klinika

Czech Republic

Interni hematologicka a onkologicka klinika

Czech Republic
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Smolej L.,Oddeleni Klinicke Hematologie | Prochazka V.,Hemato onkologicka Klinika | Spacek M.,Oddeleni Klinicke Hematologie | Obrtlikova P.,I. Interni Klinika 1 | And 3 more authors.
Vnitrni Lekarstvi | Year: 2012

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.

Gimunova O.,Klinika Anesteziologie | Bednarik O.,Interni Hematologicka A Onkologicka Klinika | Forejtova S.,Revmatologicky Ustav
Anesteziologie a Intenzivni Medicina | Year: 2015

So far, there is no consensus whether to stop biological treatment prior to elective surgery. The results of retrospective studies are very heterogeneous, because the retrospective study design and the relatively small numbers of individuals studied considerably limit the interpretation of the data. The risk of infection is greatest at the beginning of the administration of biological treatment. Current recommendations are in favour of interrupting biological treatment in the perioperative period. We present a recommendation on the management of biological treatment before surgery.

Navrkalova V.,Interni Hematologicka a Onkologicka Klinika | Kantorova B.,Interni Hematologicka a Onkologicka Klinika | Jarosova M.,Hemato Onkologicka Klinika | Pospisilova S.,Interni Hematologicka a Onkologicka Klinika
Klinicka Onkologie | Year: 2015

Chronic lymphocytic leukemia is the most common leukemia in Western countries affecting particularly elderly adults. Despite the constantly improving therapy options, chronic lymphocytic leukemia is still an incurable disease owing to considerable clinical and biological heterogeneity. Pathogenesis of chronic lymphocytic leukemia is not fully understood; however, aberrant antigenic stimulation, apoptosis deregulation and microenvironmental interactions play a crucial role in disease development. The most important molecular prognostic markers with clinical relevance include mutation status of heavy-chain immunoglobulin genes (IGHV), presence of cytogenetic aberrations and TP53 and ATM gene mutations. Recent implementation of next generation sequencing technologies has enabled more accurate analysis of both well-established and novel potential prognostic markers. The most relevant candidates are mutations in SF3B1, NOTCH1 and BIRC3 genes, which are now intensively studied with respect to their clinical importance. The other examined molecular mechanisms of chronic lympho cytic leukemia pathogenesis include deregulation of B-cell receptor signalization and abnormal regulation of gene expression by microRNA. The precise characterization of molecular abnormalities improves the risk stratification of chronic lymphocytic leukemia patients, which could possibly benefit from new treatment approaches.

Adam Z.,Interni Hematologicka A Onkologicka Klinika | Scudla V.,III. Interni Klinika Nefrologie | Krejci M.,Interni Hematologicka A Onkologicka Klinika | Cermakova Z.,Oddeleni Klinicke Biochemie FN Brno | And 2 more authors.
Vnitrni Lekarstvi | Year: 2013

Until 2011, the gold standard of treatment for patients with AL amyloidosis was the combination of alkylating cytostatics (melphalan or cyclophosphamide) and dexamethasone. For a selected group of patients under 65 years of age with only moderate damage to their body caused by amyloid and with good cardiac function (EF> 40%), high-dose chemotherapy with autologous hematopoietic cell transplantation seems to be optimal. Patients with AL amyloidosis and low bone marrow plasma cell count generally undergo the harvest of hematopoietic cells from peripheral blood, followed by high-dose chemotherapy immediately after they are diagnosed. In contrast to multiple myeloma, high-dose chemotherapy is not preceded by several months of conventional treatment. The year 2012 witnessed a release of reports about extensive experience with new drugs that were used in Phase I and Phase II clinical trials, and in isolated cases also in Phase III, for the treatment of patients with AL amyloidosis. Based on these studies it can be concluded that among the new available drugs (bortezomib, thalidomide and lenalidomide) bortezomib is the drug with the greatest curative effect in patients with AL amyloidosis; it achieved 24-37% of complete remissions in monotherapy. The greatest number of treatment responses was reported during the treatment that combined bortezomib, alkylating cytostatics and dexamethasone. This treatment showed significantly more treatment responses during the first-line drug therapy than during therapies that followed. Clinical trials with lenalidomide combined with other drugs saw a lower number of treatment responses than the number described in treatment with bortezomib combined with other drugs. That is the reason why lenalidomide combinations are not considered the optimal first-line therapy, with the exception of AL amyloidosis with bortezomib contraindication (severe neuropathy caused by AL amyloidosis). It was confirmed that lenalidomide combined with other drugs could cause remission in patients whose disease was resistant to the initial bortezomib therapy. Lenalidomide (or alternatively also thalidomide) can therefore be used as second-line therapy if bortezomib therapy proves unsuccessful, with the possibility of achieving a complete remission. The increase in the number of complete remissions brought about by bortezomib therapies in patients with AL amyloidosis poses a question about which treatment should be used for younger patients with only moderate damage to their body, i.e. high-dose chemotherapy with autologous hematopoietic cell transplantation or combined treatment with bortezomib. Additional comparative studies are required to be able to answer that question and determine which of the aforesaid therapy modalities is optimal. A question still remains whether the increase in the number of complete remissions due to bortezomib will also bring about longer survival comparable to the results of high-dose chemotherapy treatment with autologous hematopoietic cell transplantation.

Cervinek L.,Interni hematologicka a onkologicka Klinika
Onkologie (Czech Republic) | Year: 2015

Myelodysplastic syndrome is a clonal haemopoietic disorder that is manifested with a peak at the age of 65 to 72 years. The pathophysiology of the disease is associated with genetic changes in the stem cell's nucleus. In terms of diagnosis, it is essential to examine the bone marrow and provide cytogenetic and, optionally, molecular genetic testing, on the basis of which the disease is classified accurately and the patient's prognosis and optimal treatment are determined. The treatment strategy can be divided into two groups. The treatment recommended for patients with low risk consists of supportive, stimulation, or immunomodulatory therapy. The treatment of high-risk patients involves the administration of hypomethylating agents or chemotherapy with subsequent haemopoietic stem cell transplantation.

Folber F.,Interni hematologicka a onkologicka klinika | Doubek M.,Interni hematologicka a onkologicka klinika
Onkologie (Switzerland) | Year: 2013

Acute lymphoblastic leukemia in adults belongs among rare precursor malignant lymphoproliferative disorders. This paper summarizes recommendations for diagnosis and treatment, and identifies some promising new drugs to be tested in clinical trials.

Folber F.,Interni hematologicka a onkologicka Klinika | Hrabovsky S.,Interni hematologicka a onkologicka Klinika | Doubek M.,Interni hematologicka a onkologicka Klinika
Onkologie (Czech Republic) | Year: 2015

Initial symptoms at diagnosis, essential diagnostic work-up procedures, current treatment guidelines and prognosis of adult acute lymphoblastic leukemia are discussed in this review article. A separate section deals with several special subtypes of this disease and new drugs or treatment approaches available recently or tested within ongoing clinical trials.

Zackova D.,Interni hematologicka a onkologicka Klinika
Onkologie (Czech Republic) | Year: 2015

Natural course and particularly prognosis of the patients with chronic myeloid leukemia (CML) improved fundamentally during last fourteen years thanks to tyrosine kinase inhibitors (TKI) targeted therapy introduction. Currently, three TKI (imatinib, nilotinib, and dasatinib) are available for the first line treatment, and two other efficient drugs (bosutinib and ponatinib) can be used in the case of failure or intolerance of previously administered TKI. Regular and standardized treatment efficacy monitoring is crucial for appropriate and timely change of therapy when required responses are not met in given time points. Prognostic significance of early treatment switch in case of failure to achieve an early molecular response has not been established yet. Similarly, even if the data suggest possibility and feasibility of stopping TKI therapy in patients with durable deep molecular response, at present, stopping TKI should only be done in the context of clinical trials and cannot be routinely recommended into clinical practice. Allogeneic stem cells transplantation is still the only curative treatment option even in the TKI era, and should be used in the following situations: patients who fail at least 2 TKI, patients with presence of T315I mutation and patients who progress into advanced stages of the disease.

Hadrabova M.,Interni hematologicka a onkologicka Klinika
Onkologie (Czech Republic) | Year: 2015

Chronic lymphocytic leukaemia (CLL) is a low-malignant lymphoproliferative disease affecting the elderly population. It is the most frequent leukaemia in the Western world where it accounts for nearly 30 % of all leukaemias. The pathogenesis of CLL is still precisely unknown, even though much progress has recently been made in this field. Novel prognostic factors are being studied that could determine risk groups of patients requiring early and intensive therapy initiation. Up to now, however, treatment has been indicated according to the stage of the disease. In recent years, CLL treatment has been evolving rapidly. Although chemoimmunotherapy, which is capable of inducing up to several years of complete disease remission, remains the gold standard of treatment, novel drugs have emerged that are effective both in first-line treatment and in patients with disease relapse or with refractory disease. These include novel monoclonal antibodies, BCR signalling inhibitors, or Bcl-2 inhibitors.

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 relaps 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 potencial of additional elimination of remaining cancer cells. Decreased toxicity of these regimens enables treatment of patients with comorbidity and/or in higher age.

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