Treatment of adult patients with acute lymphoblastic leukemia in the Czech Republic in the period 2007-2020.

BACKGROUND: Pediatric-inspired protocols with prospective monitoring of minimal residual disease (MRD) are considered the standard of intensive treatment for adults with acute lymphoblastic leukemia (ALL). They have been used in the Czech Republic since 2007. PATIENTS AND METHODS: Two hundred and ninety-seven patients aged 18-65 years were treated at five hematology centers between 2007-2020 according to the GMALL 07/2003 protocol. This is a retrospective analysis of their treatment outcomes. RESULTS: In the Ph-negative cohort, 189 (93.1%) patients achieved complete remission, 5 (2.4%) patients were refractory, and early mortality was 3.0%. Seventy (34.5%) patients experienced relapse in a median of 10.6 months. Overall survival (OS) at 3 and 5 years was 63.5% and 55.9%, disease-free survival (DFS) at 3 and 5 years was 54.5% and 49.7%, respectively. Young adults under 35 years of age (P = 0.015), patients without initial CNS infiltration (P = 0.016), with MRD negativity before consolidation treatment (P < 0.001), transplanted in the 1st complete remission (P < 0.001), and subjects treated after 2012 (P = 0.05) had significantly better overall survival. In a multivariate analysis, MRD at week 11 was the only independent factor affecting OS (HR 3.06; P = 0.006). For DFS, baseline CNS infiltration (HR 2.08; P = 0.038) and MRD at week 11 (HR 2.15; P = 0.020) were significant. In the Ph-positive cohort, 84 (89.4%) patients achieved complete remission, 1 (1.0%) patient was refractory, early mortality was 4.3%. Twenty-six (27.7%) patients relapsed in a median of 8.6 months. Survival at 3 and 5 years was 57.2% and 52.4% for OS and 50.2% and 44.9% for DFS, respectively. Transplanted patients and patients diagnosed after 2012 had statistically better overall survival (P < 0.001). CONCLUSION: The introduction of pediatric-inspired protocols with treatment intensification according to MRD levels resulted in a significant improvement in the survival outcomes of adult patients with ALL.

[HELLP syndrome requiring therapeutic plasma exchange due to progression to multiple organ dysfunction syndrome with predominant encephalopathy, respiratory and renal insufficiency]. / HELLP syndrom vyzadující plazmaferézu pro rozvoj multiorgánové dysfunkce s dominující encefalopatií, respiracní a renální insuficiencí.

OBJECTIVE: Case report of woman with twin pregnancy complicated by HELLP syndrome which progressed to multiple organ dysfunction syndrome with predominant encephalopathy, renal and respiratory insufficiency with the need to perform repeated therapeutic plasma exchange. DESIGN: Case report. SETTING: Department of gynecology and obstetrics, University Hospital in Ostrava; Departmet of hematooncology, University Hospital in Ostrava; Department of gynecology and obstetrics, Vsetín hospital; Department of hematology and transfusion, Vsetín Hospital. RESULTS: Case of 35-year-old III gravida/II para with previously normal ongoing twin bichorionic biamniotic pregnancy in week 35+0, which was admitted to secondary care delivery room for three days lasting "flu like" symptoms and the right upper quadrant pain. She was icteric, exhausted, but normotensive (120/75 mm Hg). Acute caesarean section was performed for suspected fetal hypoxia and HELLP syndrome. The laboratory exams confirmed coagulopathy and HELLP syndrome second class during the operation. Blood loss was 800 ml. Despite standard treatment of HELLP syndrome, the condition had developed to renal insufficiency, bilateral fluidothorax, alveolar pulmonary edema, encephalopathy and hypertension. In laboratory results dominates markers of coagulopathy, thrombocytopenia and microangiopathic hemolytic anemia with presence of schistocytes. Due to multiple organ dysfunction syndrome with hemolysis of unclear origin, patient was transferred to referral hospital on sixth postoperative day. Therapeutic plasma exchange (TPEX) was promptly begun. Improvement of laboratory parameters occurred already after the first TPEX and after two days there was a significant improvement of neurological status. Nine TPEX procedures were performed. The treatment was terminated after platelet count reached 100×109/l. She was discharged from hospital 21 days after delivery. After exclusion of other clinical entities, the case was closed as postpartum thrombotic microangiopathic syndrome. CONCLUSION: Postpartum thrombotic microangiopathic syndrome includes states, which resemble HELLP syndrome with their laboratory result and clinical expression, but their behavior is different - progressively worsening with signs of disseminated intravascular coagulation and complex microangiopathy with multiple organ dysfunction. It is not responding to classic treatment of HELLP syndrome. In this cases usually improvement of patients condition follow initiation of therapeutic plasma exchange.

Biobanking strategy and sample preprocessing for integrative research in monoclonal gammopathies.

AIMS: Some types of monoclonal gammopathies are typified by a very limited availability of aberrant cells. Modern research use high throughput technologies and an integrated approach for detailed characterisation of abnormal cells. This strategy requires relatively high amounts of starting material which cannot be obtained from every diagnosis without causing inconvenience to the patient. The aim of this methodological paper is to reflect our long experience with laboratory work and describe the best protocols for sample collection, sorting and further preprocessing in terms of the available number of cells and intended downstream application in monoclonal gammopathies research. Potential pitfalls are also discussed. METHODS: Comparison and optimisation of freezing and sorting protocols for plasma cells in monoclonal gammopathies, followed by testing of various nucleic acid isolation and amplification techniques to establish a guideline for sample processing in haemato-oncology research. RESULTS: We show the average numbers of aberrant cells that can be obtained from various monoclonal gammopathies (monoclonal gammopathy of undetermined significance/light chain amyloidosis/multiple myeloma (MM)/MM circulating plasma cells/ minimal residual disease MM-10 123/22 846/305 501/68 641/4000 aberrant plasma cells of 48/30/10/16/37×106 bone marrow mononuclear cells) and the expected yield of nucleic acids provided from multiple isolation kits (DNA/RNA yield from 1 to 200×103 cells was 2.14-427/0.12-123 ng). CONCLUSIONS: Tested kits for parallel isolation deliver outputs comparable with kits specialised for just one type of molecule. We also present our positive experience with the whole genome amplification method, which can serve as a very powerful tool to gain complex information from a very small cell population.

The quality of life following allogeneic hematopoietic stem cell transplantation - a multicenter retrospective study.

UNLABELLED: Although allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers a unique curative potential, it may be connected with high treatment-related morbidity and mortality. Besides many organ complications, allo-HSCT may significantly affect quality of life (QOL). PATIENTS AND METHODS: Between January 2011 and December 2012, five hundred and ninety patients (pts) from 6 transplant centers in the Czech Republic filled in the questionnaire for the quantitative measurement of QOL using Functional Assessment of Cancer Therapy-General (FACT-G) version 4. Study cohort characteristics were as follows: 325 males, 340 pts received myeloablative conditioning, 383 pts received PBPC, representation of diagnoses; acute leukemia (n=270), bone marrow failure (n=36), chronic myeloid leukemia (n=74), myelodysplastic/myeloproliferative syndrom (n=110), lymphoproliferative disease (n=93). The median age at allo-HSCT was 43 years (range: 1.7 - 71.0), the median time from allo-HSCT to questionnaire completing was 3.8 years (range: - 0.2 - 21.6). The earliest allo-HSCT was performed in November 1989, the last in September 2012. In this retrospective study, we investigated the impact of various factors on the QOL after allo-HSCT: age, gender, diagnosis, type of conditioning, time from diagnosis to allo-HSCT, disease stage, graft type, donor type, time from allo-HSCT to questionnaire completing, GVHD, relapse. Only data from patients who were more than 3 months after allo-HSCT were used for the multivariate analysis. The overall results of the total FACT-G score (median=85.0; range: 29-108) as well as the results of each specific dimension - PWB (median=23.0; range: 5-28), SWB (median=24.0; range: 7-28), EWB (median= 19.0; range: 4-24), FWB (mean=21.0; range: 2-28) showed a value in the highest quartile of the possible evaluation. In multivariate analysis, an inferior QOL score was reported for patients with aGVHD (p=0.002), cGVHD (p<0.001), QOL decreased with increasing age (p=0.048) and increased with time elapsed since allo-HSCT (p<0.001).Allogeneic HSCT represents an important intervention into the overall integrity of the organism. In particular, the development of GVHD can cause very serious organ, but also mental problems which can significantly reduce the QOL. The QOL is steadily increasing with increasing interval from allo-HSCT but improvement and disappearance of these complications may take many years, and sometimes these effects may probably persist permanently.

Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation.

Autologous haematopoietic SCT with PBSCs is regularly used to restore BM function in patients with multiple myeloma or lymphoma after myeloablative chemotherapy. Twenty-eight experts from the European Group for Blood and Marrow Transplantation developed a position statement on the best approaches to mobilising PBSCs and on possibilities of optimising graft yields in patients who mobilise poorly. Choosing the appropriate mobilisation regimen, based on patients' disease stage and condition, and optimising the apheresis protocol can improve mobilisation outcomes. Several factors may influence mobilisation outcomes, including older age, a more advanced disease stage, the type of prior chemotherapy (e.g., fludarabine or melphalan), prior irradiation or a higher number of prior treatment lines. The most robust predictive factor for poor PBSC collection is the CD34(+) cell count in PB before apheresis. Determination of the CD34(+) cell count in PB before apheresis helps to identify patients at risk of poor PBSC collection and allows pre-emptive intervention to rescue mobilisation in these patients. Such a proactive approach might help to overcome deficiencies in stem cell mobilisation and offers a rationale for the use of novel mobilisation agents.

[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.

European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization.

The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 × 10(6) CD34+ cells/kg: 81.6%; >5.0 × 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 × 10(6) CD34+ cells/kg: 64.8%; >5.0 × 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 × 10(6) CD34+ cells/kg: 81.5%; >5.0 × 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required.

[Diagnosis and treatment of BCR/ABL-negative myeloproliferative diseases--principles and rationale of CZEMP recommendations]. / Diagnostika a lécba BCR/ABL-negativních myeloproliferativních onemocnení--principy a výchdiska doporuceni CZEMP.

In 2009, the recommendations of the Czech Collaborative Group for Ph- Myeloproliferative Diseases (CZEMP) for diagnosis and treatment of BCR/ABL-negative myeloproliferative diseases (MPD), i.e., essential thrombocythemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF) were updated and extended. The present article gives the rationale of the recommendations in full detail. The CZEMP diagnostic criteria for ET and PMF are based on histopathological (HP) findings, which must unconditionally be in line with the given clinical and laboratory characteristics of ET or of a certain stage of PMF, respectively. The platelet count is not decisive for diagnosis. In cases lacking an adequately taken and read HP finding, the Polycythemia Vera Study Group (PVSG) criteria are recommended. The diagnosis of typical PV is based on demonstration of the V617F mutation of the JAK2 gene along with a significant increase of red cell parameters. If these are close to borderline, the demonstration of increased total red cell mass (RCM) is required. In atypical cases lacking polyglobulia or elevated RCM, the HP picture of PV (in accordance with WHO description) plus JAK2 V617F mutation is satisfactory for diagnosis, or, in cases lacking JAK2 V617F mutation, the HP picture of PV along with polyglobulia (or increased RCM) is sufficient. The treatment principles of ET and other MPDs with thrombocythemia (MPD-T; i.e., the early stages of PMF and PV) are identical. The patients are stratified by their thrombotic risk (preceding thrombosis, another thrombophilic state, jAK2 mutation), presence of disease symptoms (mainly microcirculatory), platelet count and age. Only patients up to 65 years lacking the above mentioned risks with a platelet count < 1000 x 10(9)/l are considered as low-risk and do not demand cytoreducing therapy. The others are high-risk ones and have an indication for thromboreduction. In patients older than 65 years, the potentially leukemogenic drug hydroxyurea (HU) may be used. In the younger ones, the choice is between anagrelide (ANG) or interferon-alpha (IFN). In high-risk patients, the treatment goal is to maintain platelet counts below 400, and in low-risk ones, below 600 x 10(9)/l. In PV, polycythemia itself is another thrombotic risk factor. The condition is treated by bloodletting or erythrocytaphereses. If hematocrit levels < or =45 are not achieved, cytoreductive therapy using HU in patients over 65 years, or IFN in younger individuals is required. All patients with thrombocythemia in PV are high-risk and have an indication for cytoreduction. Acetylsalicylic acid is given to all patients with MPD-T with platelets < 1000 x 10(9)/l (at higher counts, hemorrhage is imminent), and to all individuals with PV, unless contraindication is present. In case of platelet count normalization, it may be withdrawn in cases of low-risk ET or PMF, not in JAK2+ PV. The treatment of advanced stages of PMF is symptomatic, with substitution of blood derivatives being the basis. The only curative treatment is allogeneic stem cell transplantation, which should not be indicated too early seeing to its risks, but also not too late--we must not allow transition into acute leukemia, which is heralded by blasts in the blood picture. The indication is the presence of any of the following criteria: values of hemoglobin < 10 g/dl, WBC < 4 x 10(9)/l and platelets < 100 x 10(9)/l, any percentage of blasts or > or = 10% immature granulocytes in the differential picture, >1 erythroblast per 100 cells--all at repeated examinations within at least a 2-month interval, and in addition, rapid progression of hepato-/splenomegaly, presence of general symptoms of the disease, portal hypertension and extensive swellings.

[Kidney failure in a patient with chronic B-lymphocytic leukaemia (B-CLL) with underlying cast nephropathy. The value of free immunoglobulin light chain identification for early diagnosis of this complication]. / Selhání ledvin u pacientky s chronickou B-lymfocytární leukemií (B-CLL) vzniklé na podklade tvorby odlitkových válcu v tubulech ledvin z monoklonálnich volných lehkých retezcu (cast nephropathy). Prínos stanovení volných lehkých retezcu imunoglobulinu pro casnou diagnostiku této komplikace.

We describe a case of an untreated female patient monitored over 8 years for chronic B-lymphocytic leukaemia (B-CLL). Over the 8 years, the patient has gradually developed severe kidney failure, even though the criteria for B-CLL treatment had not been fulfilled. Kidney biopsy revealed renal damage due to lamda free light chains cast nephropathy as well as an infiltration of renal parenchyma with B-CLL cells. It was not before this biopsy that the presence of monoclonal immunoglobulins has been investigated. Immunofixation identified free monoclonal lamda light chains in the serum and urine. Their serum concentration, quantified by densitometry, was 2.6 g/l and urine concentration was 0.5 g/l. A specific evaluation of free light chains in the serum revealed an extremely high concentration of free X light chains, over 4500 mg/l, and normal concentration of K free light chains, 10 mg/l. The aim of this report is to emphasise that monoclonal immunoglobulin may be present in B-CLL as well as other lymphoprolipherative diseases and that it may cause damage to organs, similar to multiple myeloma or monoclonal gammopathy of undetermined significance. The described case confirms poor prognostic value of monoclonal immunoglobulin free light chains in patients with B-CLL and usefulness of an evaluation of their presence in patients with B-CLL, particularly if the patients have increased creatinine level. The described case also highlights the need for evaluation of the presence of free light chains in the serum of all patients with unclear cause of renal failure.

[Essential thrombocythaemia and other myeloproliferative disorders with thrombocythaemia treated with Thromboreductin. A report from the database of register for the 1st quarter of 2010]. / Esenciální trombocytemie a jiné myeloproliferate s trombocytemií lécené Thromboreductinem. Výstupy z databáze Registru k 1. ctvrtletí roku 2010.

In the Czech Republic, anagrelid is used according to the recommendations of the Czech Working Group on Myeloproliferative Disorders for treatment ofthrombocythaemias associated with chronic myeloproliferative disorders--mainly essential thrombocythaemia and, regularly, reports are being presented from the Register of Patients Treated with Thromboreductin, most recently last year (Vnitr Lék 2009; 55: I-XII). The Register commenced in 2005 and from then it aims to determine detailed clinical and laboratory profiles of the patients. The structure of the Register has changed significantly in the course of its existence, reflecting the reports from each of the analyses conducted so far. Also, the data entry in the database improves every year and it reaches 97% on some of the items. The longest evaluation period in some of the patients is 108 months. By April 2010, the Register database contained data on 717 patients. Of these, 672 patients with the diagnosis of a Ph-negative chronic myeloproliferative disorder were evaluated. This year's analysis included the patients with essential thrombocythaemia, polycythaemia vera and primary myelofibrosis only. The analysis included 418 women and 254 men with median age of50 years. Unlike the first years, 2/3 of the current sample are non pretreated patients, meaning that the patients reach the specialized centres early in their treatment. Also, patients, and the older patients in particular, are more frequently treated with combined regimens including Thromboreductin. We increasingly observe hypertension as one of the monitored risk factors preceding the disease and laboratory parameters showJAK2 mutation in more than a half of patients while some form ofthrombotic diathesis is found in the anamnesis of 7-10% of patients. Some bleeding is observed in 1-5% of the registered patients. In comparison to the previous years, this is a decrease in the prevalence of clinical symptoms prior to the disease onset; this is very likely associated with an earlier patient diagnosis within the asymptomatic phase of the disease. Therapeutically, we achieve a fast treatment response but there still are 16.3% of sufficient afterone year of treatment. Thromboreductin dose is increasing but even in this group it does not exceeds the mean of 2.38 mg per 24 hours. Complications are observed in 6.2% of patients in the first year of therapy, and ofthese, thrombotic events in about 2.5% and (small) bleeding complications in 4% of patients. The data suggest that we still do not reach treatment response in a certain proportion of patients after a year of their therapy. Even though the care results from the analysed data improve every year, the Register helps to uncover some issues that still remain, such as treatment intensification and other treatment modifications.

[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.

[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.

[Treatment of Waldenström macroglobulinaemia--the experience of one centre]. / Lécba Waldenströmovy makroglobulinemie-- zkusenosti jednoho pracoviste.

Waldenström macroglobulinaemia (WM) is a disease the incidence of which is approximately 10 times lower than that of multiple myeloma. The incidence of WM is reported to be respectively 0.34 per 100,000 men and 0.7 per 100,000 women. It is one of the less aggressive lymphoproliferative diseases in which therapy is indicated only when the disease symptoms start to manifest. We present a retrospective analysis of patients with the symptomatic form of WM who were treated with chemotherapy in our centre over the last 9 years, i.e. 19 WM patients (of which 7 women and 12 men). The median age upon diagnosis of the symptomatic form of WM and start of treatment was 59 (51-78) years. The median follow up for all patients was 31 (7-121) months. The most frequent indication for WM treatment was anaemia in 57% (11/19), thrombocytopaenia in 21% (4/19), plasma hyperviscosity in 42% (8/19), symptomatic lymphadenopathy in 15% (3/19), and pathologic osteolysis in 15% (3/19) ofcases, respectively. Decrease in immunoglobulin concentration under the lower physiological limit is not referred to as a characteristic sign of WM, yet it was recorded in 7 out of 19 patients in our patient group and continued after chemotherapy, with the affected patients suffering from infections in remission more often than those with physiological values of immunoglobulins. 36% (7/19) patients were treated with R-FC (rituximab + fludarabine + cyclophosphamide) therapy, 15% (3/19) with FC therapy, 15% (3/19) with R-CHOP concluded by high-dose chemotherapy with autologous transplantation in 1 case, and 5% (1/19) with CHOP therapy. VAD (vancristine, ariamycine and dexamethasone) therapy was used in 10% (2/19) of patients and 10% (2/19) of patients were treated with oral chlorambucil. The first line of treatment achieved complete remission (CR) in 15% cases (3/15). Two patients who achieved CR were treated with R-FC, and one patient with VAD. Partial remission (PR) was achieved by 63% of patients (12/19). Minor response (MR) was achieved by 10% (2/19), and stable disease (SD) was recorded in 10% of patients (2/19) after initial treatment. The first relaps of the disease was recorded in 5 patients (2 of whom had PR and 3 MR) who achieved remission after additional lines of therapy. Thirteen patients are in the first PR. With a follow up median of 31 months (7-121), only 2 patients died from other than the underlying disease. Additional malignant disease was diagnosed in 3 patients: 1 colon carcinoma, 1 acute myeloid leukaemia (AML) and 1 myelodysplastic syndrome (MDS). All three received fludarabine and cyclophopsphamide as initial therapy. Of the three patients only the patient with MDS has survived and is now without any evidence of the presence of WM, i.e. in complete remission at 41 months after the start of therapy. High-dose chemotherapy with autologous transplantation was used in 2 cases, once as part of initial therapy and once as part of the therapy for the first relaps resistant to R-CHOP chemotherapy. It is not possible to determine the median of the first remission or the median of total survival due to the short follow up interval.

[Leukemogenesis and therapy of acute promyelocytic leukemia: from the worse to the most favorable subtype of acute myeloid leukemia]. / Leukemogeneza a lécba akutní promyelocytární leukemie: cesta od nejhorsího k nejpríznivejsímu typu akutní myeloidní leukemie.

The evolution of therapy of acute promyelocytic leukemia (APL) from 1964 to present is reviewed. The paper is focused on the main findings and key studies which formed current and almost standard therapeutic approach to APL. The first important development was the use of anthracyclines for the initial therapy of APL in 1967. Starting 1972, heparin was introduced into a treatment of coagulopathy and the intensity of substitutional transfusion therapy was remarkably enhanced. The main breakthrough was the initiation of differentiation therapy using all-trans retinoic acid (ATRA). The first clinical study which brought information about the effect of ATRA in APL started in China in 1986. A number of the most important subsequent studies focused on pathogenesis and therapy of APL are analyzed and reviewed. The additional considerable finding was the discovery of arsenic trioxide (ATO) therapeutic efficacy in APL and ATO is now in particular used for a therapy of relapsed APL. The publication gives also a recent insight into a leukemogenesis of APL and development of a resistance to ATRA. At the conclusion, the authors emphasize the need of early diagnosis as a one of the main conditions for successful treatment of APL.

[Coagulopathy and differentiation syndrome: the main complications of the initial treatment of acute promyelocytic leukemia]. / Koagulopatie a diferenciacní syndrom: hlavní komplikace uvodní lécby akutní promyelocytární leukemie.

Two main causes of early mortality of acute promyelocytic leukemia (APL) are rewieved, unique type ofcoagulopathy typical for APL and differentiation syndrome sometimes complicating treatment of APL with all-trans retinoic acid (ATRA) or arsenic trioxide (ATO). The information covers analysis of the patophysiologies of both conditions and also recommendations considering treatments and preventive measures.

[Relapse in acute promyelocytic leukemia and the role of hematopoietic stem cell transplantation in the treatment of APL]. / Relaps akutní promyelocytárni leukemie a role transplantace krvetvorných kmenových bunek v terapii APL.

The authors focused on relapses and transplantation treatment in APL. The incidence of relapses, their risk factors, and extramedullary relapses are reviewed. Considering treatment of relapses in APL, arsenic trioxide is now the standard treatment of APL relapse, however, treatment with gentuzumab ozogamicin should be considered when only a molecular relapse is detected. The following part of the issue is focused on the current status of hematopoietic stem cell transplantation in APL and on indications of transplantations from a modern APL therapy point of view.

[Therapy of acute promyelocytic leukemia in Czechia: results and analysis of prognostic factors]. / Lécba akutní promyelorytárni leukemie v Cesku: výsledky a analýza prognostických faktoru.

We have retrospectively evaluated a cohort of 144 patients (including 17 pediatric ones) with de novo acute promyelocytic leukemia registered in databases of institutions cooperating within the CELL group (The Czech Leukemia Study Group for Life). The patients were diagnosed according to WHO criteria from 1989 until 2006. The aim was to check how well fared the patients, the majority of whom was not included into clinical trials, in real life. Of 140 evaluable patients, 97 (69.3%) attained complete remission (CR). The projected overall survival (OS) 4 years after diagnosis was 58.9%, and 55.3% at 6 years. In 8 patients (6.0%), no antileukemic therapy at all was given (either they died shortly after admission to the ward or therapy was not feasible due to their clinical status). Of 125 patients with documented commencement of some kind of therapy, 96 (76.8%) achieved CR. Of 102 patients with induction treatment with a combination of anthracycline and tretinoin (ATRA), 84 individuals (82.4%) attained CR (typically, this cohort might have been subjected to clinical trials). This result was better than that of patients treated by chemotherapy only (n = 15; CR 46.7%; P = 0.003) or by ATRA monotherapy (n = 13; CR 62.5%; P = 0.17). Another parameter with a significant impact on attaining CR was the leukocyte (WBC) count at diagnosis: its median values in patients achieving and not achieving CR were 2.1 and 24.0 x 10(9)/l, respectively (P < 0.0001). The WBC counts affected OS as well (P = 0.0001). However, when only patients after attaining CR were evaluated, the initial WBC counts no longer affected OS (P = 0.18). Achieving CR was also influenced by the performance status (PS) 0-1 (P = 0.005), which was in turn closely correlated to WBC counts (P = 0.0006). Additional factors (most likely connected with leukocytosis) influenced attaining CR with borderline statistical significance: e.g. FAB M3v morphology, LDH serum level, fibrinogen level, presence of internal tandem duplication (ITD) of the FLT3 gene (which was strongly associated with leukocytosis and also with the short PML/RARalpha transcript resulting from the bcr3 break in the PML gene). It may be speculated that FLT3-ITD is just one of the possible factors that lead to leukocytosis. The platelet counts at diagnosis had no impact on entering CR. Thus, we have not validated the current PETHEMA risk stratification in distinguishing intertermediate and low risk patients. Our study points to a significant difference of the results obtained in real life and of the results that could be achieved in patients who were fit to enter clinical trials. Among the prognostic factors, the most important one was the WBC count, the PS (which is highly affected by the WBC count), and feasibility of administration of the most potent induction therapy with anthracyclines and ATRA.

[Brief case reports illustrate various initial courses in acute promyelocytic leukemia]. / Strucné kazuistiky ilustrující uvodní prubeh u akutní promyelorytární leukemie.

Authors present cases which illustrate a various initial symptoms and courses of patients between the first symptoms and the diagnosis of acute promyelocytic leukemia. Symptoms indicated possible serious hematological diseases are well-known: unusual bleeding, recurrent infections or infections not responded to antibiotics, fatigue, anemia symptoms. The disease progression was sometimes very rapid, however, in certain patients the symptoms were disappreciated or even minimized and the approaches were not adequate to risks resulted from newly diagnosed acute promyelocytic leukemia.