European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

[Peripheral blood cell count and inflammation-based markers in chronic rhinosinusitis]. / Zellzahl und Entzündungsparameter im peripheren Blut bei chronischer Rhinosinusitis.

OBJECTIVE: The aim of this study was to verify whether the following peripheral blood cell count and inflammation-based markers differ between various types of chronic rhinosinusitis (CRS): neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), as well as erythrocyte sedimentation rate (ESR) and C­reactive protein (CRP) levels. MATERIALS AND METHODS: In all, 386 patients had complete peripheral blood count, ESR, CRP and nasal cytology. The severity of CRS symptoms was assessed using three-stage Lund-Mackay computed tomography (CT) scores. The participants were stratified based on the results of nasal cytology and by the presence of nasal polyps (NP). The inflammation-based markers were calculated by dividing the cell numbers of the different cell types by numbers of the other cell types. RESULTS AND CONCLUSIONS: Blood leukocyte and neutrophil counts were higher in neutrophilic CRS. Differences between patients with CRS with nasal polyps (NP) and CRS without NP were significant for blood leukocytes, neutrophils, monocytes, eosinophils, CRP, NLR and MLR values. In CRS with NP, peripheral blood leukocyte, neutrophil, monocyte and eosinophil counts, as well as CRP, NLR and MLR values were higher than in CRS without NP. Our results show that all individuals with CRS could benefit from the analysis of blood counts and inflammation-based markers at the beginning of their evaluation. High levels of inflammation-based markers might guide the clinician towards planning more radical CRS therapy and use of systemic anti-inflammatory medication.

Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Background: This two-stage, phase IIa study investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin's lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. Patients and methods: Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab-containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary end point was overall response rate. Results: Ninety-two patients were enrolled: DLBCL (n = 35), FL (n = 34), other iNHL (n = 11) and MCL (n = 12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (12%) and neutropenia (12%). One patient experienced a grade 4 infusion-related reaction and eight patients (9%) experienced grade 3/4 neutropenia. No treatment-related deaths were reported. Conclusions: MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL. ClinicalTrials.gov number: NCT01685008.

Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network.

BACKGROUND: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS: We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS: The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status ≥2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of ≥1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 × 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

Two autologous transplants in the treatment of patients with Hodgkin's lymphoma: analysis of prognostic factors and comparison with a single procedure.

We summarized registry data of the long term observation of 35 patients treated with two autologous transplants. Prognostic factors for overall survival (OS) and DFS were analyzed. The OS was compared with 105 patients from a single transplant group. Two factors were significant in univariate analysis of DFS after the second transplant: response to the first transplant (complete remission (CR) versus progressive disease (PD) p = 0.041) and the disease status at the time of the second autologous stem cell transplantation (ASCT) (CR versus partial remission (PR) p = 0.004; CR versus PD p = 0.0002). In the multivariate analysis only the last of the parameters remain significant (RR 2.30, p = 0.004, 95% CI; 1.30 - 4.04). In the analysis of OS, two factors were significant in univariate analysis: status of the disease at the first transplant (PR versus PD p = 0.008) and response to the first transplant (CR versus PD p = 0.025). None of those factors remained significant in a multivariate analysis. A probability of 5-year survival after the first transplant in patients treated with two transplants was 83% (95% CI; 70 - 97%). A tendency towards better survival was seen in patients treated with two transplants (p = 0.01). The trend toward better survival from the time of diagnosis is kept for those who entered CR or PR after standard chemotherapy (p = 0.097) but not for the whole group (p = 0.13).

Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients.

BACKGROUND: The reported probability of survival of patients with Hodgkin's disease (HD) following high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is 35-65% at 5 years. The Polish Lymphoma Research Group investigated retrospectively prognostic factors for overall survival (OS) and event-free survival (EFS), and the risk of secondary malignancies in a large series of patients who underwent HDC/ASCT. PATIENTS AND METHODS: The data of 341 consecutive patients treated in 10 centers from 1990 to 2002 were collected and analyzed. RESULTS: The actuarial 5-year OS and EFS were 64% [95% confidence interval (CI) 57% to 71%] and 45% (95% CI 39% to 51%), respectively. In the multivariate model, unfavorable prognostic factors for EFS were less than partial response at the time of ASCT [relative risk (RR), 2.92 (95% CI 1.68-5.08); P<0.001] and three or more previous chemotherapy lines (RR, 2.16; 95% CI 1.42-3.30; P<0.001). These two factors were also associated with unfavorable OS (RR, 3.32; 95% CI 1.90-5.79; P<0.001 and RR, 2.34, 95% CI 1.51-3.64; P<0.001). Five-year cumulative risk of secondary malignancy was 8.4% (95% CI 2% to 13%) and the only identified risk factor was splenectomy (P=0.02). CONCLUSIONS: HDC/ASCT should be considered early in the course of disease for patients with a response after standard therapy.

High-dose chemotherapy with autologous stem cell transplantation is an effective treatment of primary refractory Hodgkin's disease. Retrospective study of the Polish Lymphoma Research Group.

We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.

[Harvesting bone marrow from the posterior superior iliac crest for transplantation]. / Pobieranie szpiku kostnego z talerzy biodrowych da celów transplantacyjnych.

The purpose of bone marrow cells harvesting is to isolate haemopoietic stem cell for the transplantation, by means of multiple punctures from the posterior iliac crest under general anaesthesia. This method is the alternative procedure for collecting circulating peripheral blood progenitor cells performed with continuous-flow cell separators. The aim of the both procedures is the collection of progenitor cells for transplantation in the number enabling reconstitution of marrow function after myeloablative therapy. The bone marrow cell harvesting is a safe measure: the infrequent complication related to general anaesthesia may occur and the simultaneous or subsequent blood transfusion is usually required.

[Diagnostics, classification and high dose chemotherapy in non Hodgkin's and Hodgkin's lymphoma]. / Diagnostyka, klasyfikacja oraz wysokodawkowana chemioterapia w NHL i chorobie Hodgkina.

Authors tried to present general concept of REAL classification, it's comparison with working formulation and example of practical approach to diagnosis of patients with lymphocytosis and splenomegaly. In a second part of this paper, indications and procedure of the high dose chemotherapy with hematopoietic stem cell support in Hodgkin's and non Hodgkin's lymphomas is summarised.

[Non Hodgkin's lymphoma--treatment of choice and the role of high dose chemotherapy]. / Chloniaki nieziarnicze--postepowanie z wyboru i rola wysokodawkowej chemioterapii.

Non Hodgkin's Lymphomas protocols currently used at the CMUJ Department of Haematology in Cracow based on updated results of randomised trials are summarised. High dose chemotherapy with hematopoietic blood stem cell support is only one of the elements of modern NHL therapy; it's effectiveness depends on optimal indications and timing of the procedure.

[Hodgkin's disease--diagnostic basis and therapy in light of randomized clinical trials]. / Choroba Hodgkina--podstawy diagnostyki i postepowanie w swietle randomizowanych badan klinicznych.

Hodgkin Disease has a relatively good prognosis and high curability due to the effectiveness of risk adapted treatment. Protocol currently used at the Department of Haematology in Cracow is based on randomised multicentre clinical trials, summarised in this paper. Proper choice of the first line treatment is most important for overall survival--no salvage therapy for resistant or recurrent disease is equally effective. High dose chemotherapy with autologous stem cell support should be considered in certain clinical situations, as partial response or relapse after conventional treatment.

[Subendocardial blood flow index in relation to selected parameters of left-ventricular function in patients with aortic valve stenosis]. / Wskaznik przeplywu podwsierdziowego w odniesieniu do wybranych parametrów czynnosci lewej komory u chorych ze zwezeniem lewego ujscia tetniczego.

The aim of our studies was to estimate the relation between the reduction of the subendocardial blood flow, expressed by DPTI/TTI ratio and the grade of aortic stenosis determined by the maximal systolic aortic gradient. Additionally the influence of subendocardial blood flow reduction of left ventricular function and ECG alterations was assessed. The analyzed data were obtained during the cardiac catheterizations in a group of 30 patients (average age 32 years). The mean value of DPTI/TTI ratio was decreased (0.49 +/- 0.2) and associated with the elevated mean value of AGmax (72.2 +/- 38.1 mmHg). Negative correlation between DPTI/TTI and AGmax (r = -0.73; p less than 0.003), DPTI/TTI and LVEDP (r = -0.53; p less than 0.005) occurred. Depression of ST-T segment in EEG and episodes of anginal pain accompanied the reduction of subendocardial blood flow. We concluded that reduction in subendocardial blood flow in patients with SA-may lead subendocardial ischaemia of the left ventricular wall with subsequent of its function.

[A preliminary assessment of the incidence of atopy at a workplace in Cracow]. / Wstepna ocena czestosci wystepowania atopii w jednym z krakowskich zakladów pracy.

Skin tests, IgE level and eosinophils percentage were determined in 337 employees of the "Hydrokop" Works in Cracow. These investigations aimed at seeking more specific markers of allergy than anamnesis and skin tests. Allergy was reported by 108 individuals (38%). Some features of atopy were confirmed in 7.5%. Skin tests were positive in 36 individuals and were related to atopy in 55%. IgE levels were 10 IU/ml--greater than 1000 IU/ml with the distribution similar to log-normal. Mean IgE concentration was relatively high (202 IU/ml, in the individuals with confirmed congenital allergy. Percentage of eosinophils exceeded 3% in 39 subjects out of which 17 reported the symptoms of allergy. IgE level and percentage of eosinophils are controversial as the markers of atopy due to the contribution of various non-allergic factors while skin tests correlate well with allergic diseases which were relatively frequent in the examined group.