[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

[Spontaneous remission of acute myeloid leukemia - a single center case reports]. / Spontánní remise akutní myeloidní leukemie - klinické prípady jednoho centra.

BACKGROUND: Acute myeloid leukemia is a malignant disease characterized by clonal expansion of immature hematopoietic cells - myeloblasts - in the bone marrow. Intensive chemotherapy treatment in elderly patients (over 60) has disappointing results. In these patients, conservative treatment, including compensation of deficiency of red blood cells and platelets by transfusions and treatment of infectious complications is recommended. Also, relatively new treatment with hypometyl agents (azacytidine, decitabine) could be used. DESIGN: The idea of this article is to present a spontaneous remission phenomenon, which has not been published in Czech literature yet. In this article, we present 2 case studies of our patients who were diagnosed with acute myeloid leukemia, were not treated with chemotherapy and spontaneously reached remission of acute myeloid leukemia. CONCLUSION: The mechanisms of the spontaneous remission remain unclear, but we assume positive effect of a severe systemic infection or previous applications of blood transfusions. Antibodies in blood transfusions and a strong immune response to sepsis may have contributed to spontaneous remission.

[Angioimmunoblastic T-cell lymphoma as a very poor-prognosis malignancy--a single centre experience]. / Angioimunoblastický T-lymfom (AITL) jako velmi nepríznivá malignita - zkusenost centra.

BACKGROUND: Angioimmunoblastic T-lymphoma (AITL) is a poor prognosis malignancy. Because of relatively rare incidence and lack of publications in Czech, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of newly diagnosed AITL patients treated at our institution between 1/2000-12/2010. RESULTS: Twelve patients with median age of 64 (43-82) years were analysed. Two patients over 80 years were treated with corticosteroids. Ten patients were treated with 6 cycles of CHOP-21 chemotherapy resulting in: 2/10 (20%) stable disease, 5/10 (50%) partial remission and 3/10 (30%) complete remission. The median EFS and OS of chemotherapy-treated patients were 8 and 10 months, resp. The EFS and OS were both significantly longer in patients who achieved complete remission within the first line of CHOP or autologous stem cells transplantation therapy: 43 vs 6 (p = 0.0052) and 46 vs 6 months (p = 0.0023), respectively. It was not possible to perform autologous transplantation in 4/7 (57%) patients in need for further reduction of the disease because of poor performance status or early progression of lymphoma and death during salvage chemotherapy. CONCLUSION: AITL is a poor prognosis malignancy with a very high risk of early relapse after CHOP induction chemotherapy. In fit patients, autologous transplantation should be performed immediately after induction chemotherapy; information about availability of stem cells donor, both in the family or any available register, should be found during the induction treatment.

[The results of patients with essentials thrombocythemia and other myeloproliferation-related thrombocythemia--a report of patients treated with Thromboreductin]. / Výsledky lécby nemocných s esentiální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductin (anagrelide) in the Czech Republic contains data concerning patients that have been treated using this drug since 2004. As of June 2009, the total number of patients was 549. The current analysis focused mainly on evaluation of anagrelide dosage needed to achieve a complete response in high-risk patients: reduction in platelet count to below 400 x 10(9)/l, which was also considered as reaching the therapeutic goal. The outcomes of the registry confirm that although anagrelide (Thromboreductin) is a very effective platelet-reducing agent, the administration of which is related to a low incidence of adverse effects and complications, the therapeutic goal is not achieved in all cases and or despite a quick treatment response, the therapeutic goal is achieved more slowly.

[What is the current treatment of patients with essential thrombocytopenia and other myeloproliferations accompanied with thrombocythemia [corrected] and what can be the predictive sign of the risk of thrombosis in such patients--a report from the registry of patients treated by Thromboreductine]. / Jak lécíme nemocné s esenciální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií a co muze být prediktivní známkou rizika trombózy u techto nemocných--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductine (anagrelid) in the contributing centres in the Czech Republic has been updated with data on the patients receiving this medication since 2004. The original purpose of the registry was to record responses to Thromboreductine therapy and adverse drug reactions in patients with essential thrombocytopenia. However, data on additional Ph negative myeloproliferations, as well as data on cytoreductive therapies other than exclusively that using Thromboreductine has also been recorded in the course of its compilation, including data on combined regimes. At present, the database contains data on 421 patients, and valid conclusions can be drawn if the level of data filling is enhanced. Evaluation has been currently focused on the analysis of the risk of development of clinical symptoms of thrombosis and on the standards of treatment from the viewpoint of the achieved treatment response. Analyses of data from the registry corroborate the special importance of the proof of JAK2 mutation, and of the test for factor V Leiden mutation, and of protein of S for the assessment of the risk of thromboembolic complications. The output of the analysis confirms that anagrelid is a very efficient thromboreductive agent the administration of which is associated with a low incidence of non-serious adverse effects (10.9%). However, in spite of a fast response to therapy, the therapeutic goal consisting in the reduction of the platelet count below 400 (or below 600) x 10(9)/l, i.e. the complete (or partial) treatment response, is relatively slow to achieve. This is likely to be due to lack of radical corrections in the dosage of the drug for different reasons.

[Essential thrombocytemia and other myeloproliferations with thrombocytemia in the data of the register of patients treated with Thromboreductin till the end of 2006]. / Esenciálni trombocytemie a dalsí myeloproliferace s trombocytemií v údajích registru pacientu lécených Thromboreductinem do konce roku 2006.

Since 2005, registers of patients treated with Thromboreductin (anagrelid) kept by some centres in the Czech Republic have been supplied with data concerning patients whose treatment with this preparation started in 2004. The purpose of the register is to record responses to therapy by Thromboreductin and adverse events in patients with essential thrombocytemia and other myeloproliferations, and to subsequently analyse the data. Another objective is to detect predisposition to clinical symptomatology and disease complications. Apart from thrombocyte count, additional risk factors are monitored. The database currently contains data for 336 patients. Initial analyses of data from the register point to the fact that anagrelid is a highly effective thromboreductive agent the administration of which is associated with relatively low incidence of adverse events (11.8 %) of mild and usually transitory nature. The therapeutic objective is attained at a relatively slow rate (according to overall stratification under 400 or under 600 x 10(9)/l thrombocytes), which is probably due to insufficient dose adjustment.

[Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR]. / Anagrelid v lécbe esenciální trombocytemie a dalsích myeloproliferací s trombocytemií sledovaných v registru pacientu v CR.

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment.

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

[Allogenic transplantation of bone marrow in patients with chronic myeloid leukemia 1991-1995 and 1996-1998. Experience at the Hematology-Oncology Clinic of the University Hospital in Plzen]. / Alogenní transplantace kostní drene u pacientu s chronickou myeloidní leukémií v období 1991-1995 a 1996-1998. Zkusenosti Hematologicko-onkologického oddelení FN Plzen.

The authors compare the results of allogenic bone marrow transplantations of relatives in patients with chronic myeloid leukaemia during the initial years of the transplantation programme 1991-1995 (group 1, 15 patients) with results achieved in 1996-1998 (group 2, 30 patients) and evaluate the effect of changes concerning supportive treatment and new diagnostic methods. The age median of group 1 was 35 years, the median age of group 2 46 years. In other parameters the groups were comparable. In 1991-1995 a high transplantation mortality by the 100th day was recorded (40% as compared with 17%) and a higher incidence of stage III and IV of the acute reaction of the graft against the host (GVHD) in group 1 (20% vs. 6%). In group 2 there was a higher transplantation mortality after day 100 associated with a more frequent chronic GVHD (0% vs. 16.5%). The total survival is insignificantly better in group 2 (60% in group 1 survive with a median of 58 months follow up and 67% of group 2 with a median follow up of 33 months). Group 2 comprises however older patients. In the improved early transplantation mortality participated new methods, a change of the posttransplantation immunosuppression, experience with care of transplanted patients and better collaboration with other medical disciplines. The authors did not observe a substantial effect of changes in the basic supportive treatment on results of transplantation. Late transplantation mortality associated in particular with a higher incidence of chronic GVHD could be in the authors' opinion reduced by longer administration of immunosuppression after transplantation, in particular in older patients.

Allogeneic BMT in patients above 45 years of age: a single center experience.

Increasing age has been reported to be associated with worse outcome and higher occurrence of complication after allogeneic bone marrow transplantation. We analysed a cohort of 39 patients between the ages of 45 and 57 (median 49 years) with different hematologic malignancies who had undergone BMT in our institution over the preceding 4 years. Pretransplant conditioning consisted of Bu/CY2, GVHD prophylaxis of a combination of cyclosporine and "short" methotrexate. At present 54% of patients remain alive (with a median follow-up 44 months), the probability of survival at 5 years is 53% (5-year DFS 78%). The 5-year survival probability in the control group of younger patients is 53% (P = 0.8003). Main causes of death were GVHD (4 patients, 10%), relapse (5 patients, 13%) and infection (6 patients, 15%). The incidence of acute GVHD grade II-IV was 51% (grade III-IV 0% patients), the incidence of chronic GVHD 49% (limited 18% and extensive 31% patients). Our results suggest that allogeneic BMT can be performed in patients above the age of 45 years with acceptable morbidity and mortality, especially if a family HLA matched donor is available.

Autologous CD34+ cells transplantation after FAMP treatment in a patient with CLL and persisting AIHA: complete remission of lymphoma with control of autoimmune complications.

A 48-year-old male with CLL and concomitant AIHA unresponsive to chlorambucil was treated with fludarabine. The remission of CLL and improvement of the AIHA was achieved, but the patient remained steroid dependent. Therefore, high-dose chemotherapy followed by CD34-selected autologous peripheral blood stem cells transplantation was performed and this led to long-term clinical, immunophenotypic and molecular remission with disappearance of AIHA. Twenty-three months later, the CLL recurred with signs of AIHA. In this patient with AIHA, HDC and selected CD34+ cells completely, though temporarily, controlled both CLL and associated immune complications. This case illustrates the potential application of this approach in the management of CLL patients with immune complications.

Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow.

We report 17 cytopenic patients with myelodysplastic syndrome (MDS) of refractory anaemia (RA) subtype with hyper-, normo- or hypo-cellular bone marrow (BM), who were treated with cyclosporin A (CyA). Substantial haematological response was observed in 14 patients (82%): their anaemia improved and all transfusion-dependent patients achieved transfusion independence. Complete trilineage recovery was observed in four patients (23%). The CyA therapy has not yet failed in any of the 14 successfully treated patients during follow-up times ranging from 5 to 30 months. CyA was well tolerated in 14 patients; serious side-effects required termination of the therapy in three patients in whom the blood count rapidly deteriorated to former levels upon cessation of therapy. Two patients benefited from a combination therapy of CyA and erythropoietin. Six patients experienced various autoimmune phenomena. CyA could thus offer an alternative treatment for certain MDS patients with RA regardless of hyper-, normo- or hypo-cellularity of bone marrow (BM). The mechanism of the beneficial effect of CyA is discussed and remains the subject of an ongoing study.

[Mixed myelodysplastic and myeloproliferative syndromes]. / Smísené myelodysplastické a myeloproliferativní syndromy.

BACKGROUND: An injury to the hemopoietic stem cell may lead to the aplasia of hemopoiesis, myelodysplasia and to an unregulated myeloproliferation. There is not a strict demarcation of them, so that mixed syndromes can develop as are hypoplastic syndromes on one side and mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) on the other side. METHODS AND RESULTS: Among our 616 pts with MDS we looked for those cases, who had beside myelodysplasia signs of myeloproliferation with increased number of blood cells. They were examined in detail including bone-marrow histology, bone marrow cultivation, cytogenetics and bcr-abl gen. Signs of MDS-MPS were found in 22 patients at the first contact with the patient (13 patients had thrombocytemia and 9 patients had leukocytosis). Further 7 patients were diagnosed as MDS, proliferative syndrome developed after several months (MDS-MPS in evolution). The level of thrombocytemia was relatively stable, the number of leukocytes was progressive. All subtypes of MDS were found. All subjects had variable degree of anemia. Ring-sideroblasts and myelofibrosis were frequent finding in MDS-MPS. Men prevailed in patients with leukocytosis. Cytogenetic and cultivation findings were similar to MDS cases, deletion of long arm of chromosome 20 was present in 3 patients. Five patients transformed to acute myeloid leukemia. CONCLUSIONS: Sings of myelodysplasia and myeloproliferation were found in 4% of our MDS patients, designated as mixed myelodysplastic and myeloproliferative syndrome (MDS-MPS). In this syndrome beside evident signs of myelodysplasia thrombocythemia or leukocytosis with the release of bone marrow precursors are present. In only one case polycythemia was encountered.

[Monocytosis and myelomonocytic dysplasia in myelodysplastic syndrome]. / Monocytóza a myelomonocytární dysplazie u myelodysplastického syndromu.

Myelodysplastic syndrome (MDS) is frequently associated with monocytosis in the blood and myelomonocytic dysplasia in the bone marrow. In two groups of patients with MDS, all subtypes excluding CMML, the authors demonstrated that monocytosis was present in 15% of the patients in group I according to the haemogram at the time when the diagnosis was established and in 19% in group II where it was required that at least in half the haemograms throughout the course of the disease there were more than 10% monocytes. No difference was found in the prognosis of patients with monocytosis, as compared with patients with monocytopenia as regards the life span and frequency of transformation into AL. The cytogenetic and cultivation findings did not differ either. In some instances, in particular in patients with RA and RAS significant monocytosis was not associated with the expected proliferation of monocytoid cells in bone marrow. The authors assume that proliferation and differentiation of germ cells in the monocytic series is easier than in the granulocytic series and that monocytosis can be considered a manifestation of substituted neutropenia. The work indicates the difficulties associated with the differential diagnosis of RA, RAS and RAEB with monocytosis, MDS with a dominating change of the type of myelomonocytic dysplasia and CMML proper.

[Treatment of myelodysplastic syndrome using continual subcutaneous infusion of low doses of cytosine arabinoside]. / Lécba myelodysplastického syndromu kontinuální podkozní infúzí nízkých dávek cytosin arabinosidu.

The authors summarize their experience with the administration of small doses of cytosine arabinoside continuously by subcutaneous infusion in 13 patients with myelodysplastic syndrome. Alcysten Spofa was administered in doses of 20 mg/sq.m per day for 5-17 days in one cycle. A total of 26 therapeutic cycles were administered. Favourable responses were obtained in four patients, partial results were achieved in two patients; in seven instances treatment produced no response. The authors compare also the results obtained in this group with a previous group of 11 patients treated with small doses of cytosine arabinoside, which was administered intermittently, i.e. twice a day by the subcutaneous route. Continuous administration did not produce more favourable therapeutic results, it caused however a larger number of infections and haemorrhagic complications as compared with intermittent administration. The authors recommend administration of small doses of cytosine arabinoside in patients with prognostically adverse types of myelodysplastic syndrome - intermittently 10 mg subcutaneously twice a day for 14-21 days.

[Treatment of medium and highly malignant non-Hodgkin's lymphoma with combined chemotherapy using methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone and bleomycin (protocol MACOP-B)]. / Lécba stredne a vysoce maligních nehodgkinských lymfómu kombinovanou chemoterapií metotrexátem, adriamycinem, cyklofosfamidem, vinkristinem, prednisonem a bleomycinem (protokol MACOP-B).

Combined chemotherapy, protocol MACOP-B, was administered to 21 patients with non-Hodgkin lymphoma (NHL) with a medium or high grade of malignity, clinical stage II-IV. Complete remission was achieved in 17 patients (81%), in one instance partial remission was induced. One patient died from a cardiovascular and one from a thromboembolic complication during treatment. In one patient the results were not evaluated. Three patients developed severe granulocytopenia which called for reduction or delay of treatment and a septic condition developed. In addition to myelosuppression the main complications were stomatitis and mycosis. No death caused by infectious or haemorrhagic complications was recorded. The described chemotherapy is recommended in particular in immunoblastic lymphomas, diffuse lymphomas from cleaved and non-cleaved cells and diffuse lymphomas with mixed cellularity.