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.
- Klíčová slova
- acute lymphoblastic leukemia, hematopoietic stem cell transplantation, minimal residual disease, pediatric-inspired protocol, treatment, type 2 diabetes,
- MeSH
- akutní lymfatická leukemie * terapie MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- přežití bez známek nemoci MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- reziduální nádor diagnóza MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
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.
- Klíčová slova
- DNA, HAEMATO-ONCOLOGY, METHODOLOGY, MYELOMA,
- MeSH
- DNA izolace a purifikace MeSH
- konzervace krve metody MeSH
- krevní bankovnictví metody MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- odběr vzorku krve metody MeSH
- paraproteinemie krev MeSH
- reagenční diagnostické soupravy MeSH
- RNA izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA MeSH
- reagenční diagnostické soupravy MeSH
- RNA MeSH
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.
- Klíčová slova
- HELLP syndrome, acute kidney injury multiple organ dysfunction syndrom., encephalopathy, hemolysis, plasmapheresis, postpartum thrombotic microangipathic syndrome,
- MeSH
- císařský řez MeSH
- dospělí MeSH
- HELLP syndrom terapie MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- multiorgánové selhání * MeSH
- nemoci mozku * MeSH
- renální insuficience * MeSH
- těhotenství MeSH
- výměna plazmy * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- FACT-G., QOL, allogeneic, transplantation,
- MeSH
- dospělí MeSH
- homologní transplantace MeSH
- kvalita života psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli patologie MeSH
- průzkumy a dotazníky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk škodlivé účinky psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
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.
- MeSH
- autologní transplantace MeSH
- lidé MeSH
- lymfom terapie MeSH
- mnohočetný myelom terapie MeSH
- mobilizace hematopoetických kmenových buněk metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
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.
- MeSH
- bcr-abl fúzní proteiny analýza MeSH
- filadelfský chromozom * MeSH
- lidé MeSH
- myeloproliferativní poruchy diagnóza genetika metabolismus terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Názvy látek
- bcr-abl fúzní proteiny MeSH
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.
- MeSH
- chronická lymfatická leukemie komplikace MeSH
- ledviny patologie MeSH
- lehké řetězce imunoglobulinů krev MeSH
- lidé MeSH
- renální insuficience diagnóza etiologie imunologie patologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- lehké řetězce imunoglobulinů MeSH
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.
- MeSH
- bcr-abl fúzní proteiny * MeSH
- esenciální trombocytemie diagnóza genetika terapie MeSH
- lidé MeSH
- myeloproliferativní poruchy diagnóza genetika terapie MeSH
- polycythaemia vera diagnóza genetika terapie MeSH
- primární myelofibróza diagnóza genetika terapie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- bcr-abl fúzní proteiny * MeSH
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.
