Improvement in the outcomes of mantle cell lymphoma in the last decade: a real-life non interventional study of the Croatian Cooperative Group for Hematologic Diseases.

AIM: To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 (recent cohort). METHODS: The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort. RESULTS: The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS. CONCLUSION: In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.

Analysis of the influence of various factors on anemia in patients with lymphoid malignancies.

Anemia is a frequent complication of lymphoid neoplasms as a result of the disease and myelotoxic chemotherapy, and has a significant impact on treatment outcome, survival and quality of life. The aim of this study was to investigate clinical characteristics of anemia in lymphoid malignancies and to assess the need of anemia treatment in the context of modern therapeutic possibilities. Fifty-five patients (32 female and 23 male) with non-Hodgkin's lymphoma (NHL, n = 30), chronic lymphocytic leukemia (CLL, n = 8) and multiple myeloma (MM, n = 17) were included in the study. The influence of age, sex, type of malignancy and chemotherapy on the prevalence, severity and type of anemia before and after chemotherapy was analyzed. The prevalence of anemia was 51.02% before (A1) and 55.31% after (A2) chemotherapy. Women had a higher prevalence of anemia than men (63% vs. 43%), but the severity was higher in men at the beginning (103 vs. 99 g/L Hb) and at the end of treatment (101 vs. 89 g/L Hb). The highest prevalence of anemia was found in MM (69%), followed by NHL (44.4%) and CLL (40%) before chemotherapy, and in MM (68.7%), CLL (42.9%) and NHL (20.8%) after chemotherapy. The prevailing anemia was anemia of chronic disease (53.8%), followed by anemia due to multiple causes (anemia of chronic disease + iron deficiency anemia or anemia of chronic disease + hemolytic anemia; 30.7%), anemia due to iron deficiency (11.5%) and hemolytic anemia (7.6%). The prevalence of anemia as a consequence of the disease is high in lymphoproliferative disease, but there was no significant rise under chemotherapy, even showing a decline in NHL patients (44% vs. 21%), however, the severity of anemia increased. Since stage 1 anemia according to the WHO prevailed, only a small number of patients required transfusion therapy. About 27% of all patients had hemoglobin values <100 g/L during chemotherapy and could be candidates for erythropoiesis-stimulating agent treatment.

[Systemic fungal infections in immunocompromised patients]. / Sistemske gljivicne infekcije u imunokompromitiranih bolesnika.

Opportunistic fungal infections are becoming more frequent complications during cancer therapy, after organ transplantation and in AIDS infections, especially after better control of bacterial infections in immunocompromised patients. Periods of prolonged neutropenia with neutrophil count less than 0.5 x 10(9)/L longer than 7 days, are the most important risk factors for the development of systemic fungal infections. Especially susceptible are the patients during treatment of acute leukemia, or after bone marrow transplantation. The most frequent causing agents of systemic fungal infections are Candida and Aspergillus species, than Cryptococcus neoformans and Mucor. Some other unusual species such Fusarium, Trichosporon, non-albicans Candida species of Candida are becoming more frequent, and is frequently resistant to conventional therapy. The difficulties in early and precise diagnosis of fungal infections, and the lack of adequate and efficient drugs are responsible for the high mortality of immunocompromised patients, even in potentially curable diseases. The recognition of risk factors, introduction of prophylactic measures, application of empirical antifungal therapy, are the procedures for the reduction of morbidity and mortality of invasive fungal infections. Fluconazole administration in prevention of systemic fungal infections, has become the standard approach, especially after bone marrow transplantation, while the oral itraconazole solution, has even more extended activity. Fluconazole appears successful also in the treatment of systemic Candidiasis. Conventional amphotericin-B is still the "gold standard" in the treatment of fungal infections. The new lipid formulations of amphotericin-B, intravenous itraconazole, has an identical efficacy, but are less toxic than conventional amphotericin-B. Several new promising agents are in the stage of clinical investigation like voriconazole, caspofungin, mycafungin and some other.

[Risk factors for invasive fungal infections during intensive chemotherapy of acute leukemia--retrospective study]. / Cimbenici rizika invazivnih gljivicnih infekcija tijekom intenzivne terapije akutnih leukemija--retrospektivna studija.

AIM: The incidence, outcome and risk factors for developing invasive fungal infection were retrospectively analyzed in 150 patients with acute leukemia during intensive cytostatic therapy. PATIENTS AND METHODS: Patients with and without the diagnosis of fungal infection were compared according to age, sex, diagnosis, stage of disease, type of therapy, antimicrobial prophylaxis, duration of febrile episodes, duration of antimicrobial therapy, duration of antifungal therapy, chest x-ray findings, results of surveillance cultures for fungal species isolation, clinical diagnosis at discharge from hospital, and autopsy findings. Clinical findings in patients with confirmed fungal infection on autopsy were analyzed separately. RESULTS: The incidence of fungal infection according to clinical diagnosis was 38.5%. The incidence among patients who died during therapy at autopsy was 78.5%. The incidence of Candida and Aspergillus infections at autopsy was 40% and 60%, respectively. Specific incidence could not be determined during life. The mortality was 59% in the group of patients with fungal infection, and 43% in the group of patients without fungal infection. During the study, an increase in the rate of fungal infection as well as a trend to prolonged survival of these patients were observed. On multivariate analysis, independent risk factors associated with a greater incidence of fungal infection were duration of hospitalization (p=0.04), duration of granulocytopenia with granulocyte count less than 0.5x10(9)/L (p=0.05), number of febrile episodes (p=0.01), duration of febrile episode (p=0.001), intestinal decontamination (p=0.02), duration of antibiotic therapy (p=0.01), positive chest x-ray finding (p=0.001), and year of therapy (p=0.02). On univariate analysis, a greater incidence of fungal infections was also associated with younger age, acute lymphatic leukemia, newly diagnosed disease and second relapse of the disease. The occurrence of fungal infections showed no correlation with the type of therapy, number of chemotherapy cycles, type of fungal species isolated from particular locations and frequency of colonization at particular locations. However, the number of colonized locations and number of fungal species was two to three times greater in patients with than in those without fungal infection. CONCLUSIONS: Fungal infections are becoming an increasing problem during intensive therapy of acute leukemia and contribute to poor therapy outcome. The diagnosis of fungal infection during life is extremely difficult and frequently late. There is the need of a more precise diagnostic test that would provide earlier diagnosis. The knowledge of risk factors is helpful in the diagnosis and therapy of fungal infections. The suspicion of fungal infection in patients at risk justifies the introduction of antifungal therapy and contributes to better therapeutic outcome.

A model of oncologic care in general medicine.

The problems related to cancer and its control initially manifest in local community, and general practitioners are those who most commonly have to face them there. The aim of the study was to develop a program of comprehensive oncologic care for primary care physicians, which would be highly professional, efficient, economically justified and feasible, with the ultimate goal of upgrading the target population health and quality of life. Opinions on the priorities and intensity of work in particular activities of general practitioners in the field of oncologic care were obtained from 54 Croatian experts in oncologic care. An Expert Opinion was designed to collect oncologists' opinions by use of Delphi method. The study was performed in two runs, yielding a high rate of accordance among the oncologists. 38 of 54 participants responded in the first run, and 40 of 54 (74%) responded in the second run. The results indicated pain therapy and terminal care to be given highest priority, whereas measures of primary prevention ranked first as a group. There was a unanimous agreement that current activities of primary care physicians in the field of oncologic care were not satisfactory, and that they should take the role of a coordinator of the oncologic care of both individual patients and the population at large. The study showed that a model of oncologic care applicable throughout the country could be developed by combining data from a small health care office with the knowledge of renowned experts in the field.