Screening and monitoring of the BTKC481S mutation in a real-world cohort of patients with relapsed/refractory chronic lymphocytic leukaemia during ibrutinib therapy.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL). Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance. To assess the correlation between disease progression, and the emergence and temporal dynamics of the most common resistance mutation BTKC481S , sensitive (10-4 ) time-resolved screening was performed in 83 relapsed/refractory CLL patients during single-agent ibrutinib treatment. With a median follow-up time of 40 months, BTKC481S was detected in 48·2% (40/83) of the patients, with 80·0% (32/40) of them showing disease progression during the examined period. In these 32 cases, representing 72·7% (32/44) of all patients experiencing relapse, emergence of the BTKC481S mutation preceded the symptoms of clinical relapse with a median of nine months. Subsequent Bcl-2 inhibition therapy applied in 28/32 patients harbouring BTKC481S and progressing on ibrutinib conferred clinical and molecular remission across the patients. Our study demonstrates the clinical value of sensitive BTKC481S monitoring with the largest longitudinally analysed real-world patient cohort reported to date and validates the feasibility of an early prediction of relapse in the majority of ibrutinib-treated relapsed/refractory CLL patients experiencing disease progression.

[Low mean cell hemoglobin is a reliable marker for iron deficiency screening]. / Az alacsony átlagos vörösvértest-hemoglobin alkalmas a vashiány szurésére.

INTRODUCTION: Screening for iron deficiency, which affects a significant proportion of the population, is a burning issue in the health care system. AIM: The aim of the authors was to examine whether low mean cell hemoglobin concentration measured by automated hematology analyzers is a suitable screening parameter for iron deficiency. METHOD: The data for this study included a total of 247,705 complete blood counts and 10,840 tests with different parameters of iron metabolism. Patients were evaluated at Somogy County Kaposi Mór Teaching Hospital during a period of 30 months between January 1, 2013 and June 30, 2015. Low cell hemoglobin values were analyzed with iron metabolism parameters measured simultaneously. RESULTS: A total of 830 patients whose iron metabolism parameters were measured simultaneously had low mean cell hemoglobin (<28pg). Of the 830 patients, 679 (82%) had both low mean cell hemoglobin and iron deficiency, while in 126 hemodialysed patients (15%), 8 patients with myelofibrosis, and 5 patients with rheumatic arthritis had low mean cell hemoglobin without iron deficiency. In the remaining 6 patients the cause of low mean cell hemoglobin or iron deficiency was not identified. CONCLUSIONS: Based on these findings the authors conclude that mean cell hemoglobin may be a reliable screening marker for iron deficiency.

Rare primary extranodal lymphomas: diffuse large B-cell lymphomas of the genital tract.

Primary non-Hodgkin's lymphoma (NHL) of the genital tract is a rare entity. Etiology and pathogenesis of these NHLs are unknown, although there might be a possible association between chronic inflammation and lymphomas. The most common histological subtype is the diffuse large B-cell lymphoma. We report two cases of uterine lymphoma and one case of prostate lymphoma in this paper. The symptoms and the differential diagnosis are also discussed. Because of the low incidence, there is no widely accepted consensus on its treatment. We demonstrate that the rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP) chemoimmunotherapy is a good and tolerable treatment option in all cases. The two young patients are disease-free nowadays; the older patient with poor prognostic histological-type lymphoma relapsed in a short time and died after second relapse. A multicenter analysis is necessary to evaluate the long-term results of chemoimmunotherapy in these rare extranodal lymphoma entities.

[Primary gastrointestinal non-Hodgkin's lymphoma in two Hungarian regions]. / Pimer gastrointestinalis non-Hodgkin-lymphoma két magyarországi régió beteganyaga alapján.

UNLABELLED: Over the past few decades, the occurrence of adult onset non-Hodgkin's lymphoma has significantly increased. The patient population involved is very heterogeneous, with different clinical and morphological manifestations. In addition to the most typical nodal involvement, extra-nodal manifestations are also frequent, affecting, most often, the gastrointestinal tract, the central nervous system and the skin. The treatment strategy for non-Hodgkin's lymphoma has changed over the past decade: chemo-immunotherapy has largely taken over surgical intervention, the dominant treatment option of the past. METHODS: The authors present their experience with 48 patients with non-Hodgkin's lymphoma, affecting the gastrointestinal tract, treated in Kaposvár, in the Kaposi Mór Teaching Hospital and in Gyula, in the Pándy Kálmán County Hospital. Demography: 27 female, 21 male; mean age: 67.8 years. Localization, pathological classification and the international prognostic index (IPI) have been analysed and correlated with the clinical response to different therapeutic strategies. RESULTS: The most frequently involved GI organ was the stomach ( n = 26), with the dominant histological type of diffuse large B-cell lymphoma. Fourty-six patients received chemo-immunotherapy, 6 received radiotherapy, 3 patients were primarily treated with Helicobacter pylori eradication therapy, and 4 patients were referred for stomach resection. A complete remission was achieved in 68% of the patients, a partial remission in 13%, while 19% did not show clinical response. Based on the international prognostic index, the majority of the patients fulfilled criteria of low or high intermediate risk categories, with an IPI average of 2.68. Patients with upper gastrointestinal tract involvement carried the best prognosis (IPI: 2.0); at the same time, patients with stomach lymphoma achieved the highest rate of remission (73%). CONCLUSIONS: With chemo-immunotherapy the chances of a complete remission have significantly improved over the past decade, thus a significant portion of non-Hodgkin's lymphomas involving the gastrointestinal tract can be cured. IPI index represents the most recognised indicator for assessing the prognosis of non-Hodgkin's lymphoma. Patients who achieved complete remission had the lowest prognostic index in this cohort; nevertheless, numerous data indicate that factors other than the IPI can also have an impact on patients' response to treatment.

Prolonged survival using anti-CD20 combined chemotherapy in primary prostatic intravascular large B-cell lymphoma.

Here we report a case of a 73-year-old man with primary intravascular large B-cell lymphoma localized to the prostate. Total prostatectomy was performed due to a benign adenoma suggested by ultrasonography. The diagnosis of IVLBL was obtained incidentally from the prostatectomy specimen. Eight months after the initial R-CHOP chemotherapy a relapse was detected in the left inguinal lymph node, where histologic examination revealed common diffuse large B-cell lymphoma with minimal intravascular component. The second complete remission was achieved by R-IEV therapy. Five months later a second relapse occurred and the patient died in the widespread disease and pneumonia. Primary prostate IVLBL is extremely uncommon; to date only four cases have been described. This is a well documented case, where we also confirmed that the initial primary IVLBL and the secondary lymph node involvement are clonally related. Successful treatment depends on early diagnosis of IVLBL, aggressive chemotherapy and the fact that IVLBL should be considered as a generalized disease in spite of negative staging results.

[Imatinib therapy in chronic myeloid leukemia]. / Krónikus myeloid leukaemiás betegeink imatinibkezelése.

UNLABELLED: Chronic myeloid leukemia is a malignant clonal alteration of the pluripotent hemopoietic stem cell. The genetic hallmarks of the disease are the t(9,22) (Philadelphia chromosome), registered by conventional cytogenetics in more than 90% of all chronic myeloid leukemia cases and the active tyrosine kinase protein encoded by bcr-abl fusion gene. The constitutively active tyrosine kinase is currently accepted to be the cause of chronic myeloid leukemia. The introduction of imatinib has considerably changed the treatment of chronic myeloid leukemia. Prior studies demonstrated high rates of cytogenetic responses in all phases of the disease. METHODS: The authors evaluated the cytogenetic and molecular responses of 21 chronic phase chronic myeloid leukemia patients who were consecutively admitted to their center. 13 of them were primarily treated with imatinib, and the other 7 were heavily pretreated with interferon alpha, cytarabine, all-trans-retinoic acid. Hydroxyurea pretreatment was routinely introduced in all patients until complete hematologic remission. Peripheral blood sample in every 3 months were collected for quantitative real-time polymerase chain reaction, and bone marrow aspirate in every 6 months for conventional cytogenetics. RESULTS: Hematologic remission could have been achieved with hydroxyurea pretreatment in each patient. Complete cytogenetic remission at the 6th month and major molecular response at the 12th month were observed in each patient. CONCLUSIONS: Imatinib treatment caused complete cytogenetic response and major molecular response in each chronic phase chronic myeloid leukaemia patient in our group. Hydroxyurea might have some effect on the rapid and deep cytogenetic and molecular responses, observed in the primary imatinib-treated group.

Successful treatment of a primary uterine B-cell lymphoma with rituximab-CHOP immunochemotherapy.

We report the case of a 26 year old patient with a primary, Ann Arbor stage IE, diffuse large B-cell lymphoma of the uterine corpus. The patient was admitted to our hospital because of a one year history of vaginal contact bleeding. Final diagnosis was based on the histological and immunohistochemical evaluation of a specimen obtained by fractionated cervical and uterine curettage. Further staging has not revealed any other localization of the disease. Antilymphoma treatment was started with CHOP combined with rituximab and resulted complete remission. This is the first reported case of an uterine lymphoma treated by rituximab-based immunochemotherapy.

[Neutropenia and sepsis in hematologic patients]. / Neutropenia és szepszis a hematológiai osztályon: a Kaposi Mór Oktató Kórház tapasztalatai.

INTRODUCTION: The neutropenic patient's infections are challenging problems for modern medicine. The increasing number of iatrogenic neutropenia, the invasive procedures and the growing resistance to antibiotics and antimycotics make the treatment of sepsis difficult. The aim of this study was to analyse the frequency and mortality of neutropenic infections in hematologic patients. METHODS AND RESULTS: In the department of the authors 146 patients with sepsis were diagnosed out of 2173 treated patients in 24 months (67/1000 patients). 78 of them were neutropenic (absolute neutrophil count below 0,5 G/I) and 63 were severe neutropenic (absolute neutrophil count below 0,1 G/I). Sepsis occurred on the 10-11th day of neutropenia. 45% of positive hemoculture were caused by Gram positive bacteria, 30% by Gram negative bacteria, 10% by fungi and 15% were polymicrobic infections. The overall mortality was 36%, but in the severe neutropenic group it was about 60%. CONCLUSIONS: These results show that despite of the use of new, broad spectrum of antibiotics and antimycotics in neutropenic patients with sepsis, it is difficult to treat these patients.

Severe hemolytic anemia and acute psychosis caused by Clostridium perfringens sepsis.

BACKGROUND: Clostridium perfringens septicaemia with massive hemolysis is well known. The infection induced acute hemolytic attack frequently occur in chronic corpuscular hemolytic anemias. Alterations in mental status are common in septic patients. CASE REPORT: The case of a 39-year-old woman with a history of chronic corpuscular hemolytic anemia, experiencing weakness, pallor, somnolence is presented. Hypothermia and an acute paranoid psychotic episode subsequently developed in the hospital. C. perfringens sepsis was detected from blood cultures. The patient was cured by penicillin and clindamycin. Her symptoms disappeared and there was total resolution of toxic encephalopathy according to the brain MRI after 6 weeks. CONCLUSION: This report discusses the possible explanation of clostridial sepsis the role of brain MRI in the sepsis-induced organic psychosyndromes and underlines the need for obtain blood cultures in hypothermia suggestive to sepsis.

Effect of retinoic acid treatment on cytogenetic remission of chronic myeloid leukaemia.

The cytogenetic responses during the first chronic phase of 11 patients with chronic myeloid leukaemia (CML) treated with all-trans retinoic acid (ATRA) + interferon (IFN) were compared with those of 9 other CML patients treated with IFN alone. Metaphase and interphase cytogenetics and a semi-quantitative polymerase chain reaction were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + IFN group were withdrawn, one of them because of IFN intolerance, and the other because of non-compliance. Of the 9 remaining ATRA + IFN-treated patients 6 exhibited major cytogenetic responses, 3 of which were complete. Of the 9 patients treated with IFN alone, only 2 showed major cytogenetic responses. No severe adverse effects were observed. The preliminary results suggest that the ATRA + IFN combination may be superior in achieving cytogenetic remission in the first chronic phase of CML.