Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases.

This international retrospective study of 593 Splenic Marginal Zone Lymphoma (SMZL) patients aimed to identify factors that determine treatment initiation and influence lymphoma-specific survival (LSS). Logistic regression was used to identify the factors associated with treatment. A Cox regression was used to analyse LSS in a derivation cohort of 366 patients. This produced a prognostic index (PI) and enabled the identification of three risk groups. The resulting stratification was validated in another cohort of 227 patients and compared with the Interguppo Italiano Linfomi (IIL) score in the group of 450 patients for whom all the required data were available using an extension of the net reclassification improvement. Haemoglobin concentration (Hb), extrahilar lymphadenopathy and hepatitis C virus status were associated with the initiation of treatment. Hb, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy were independently associated with LSS. Three risk groups with significantly different five-year LSS (94%, 78% and 69%, respectively) were identified. This stratification (named HPLL on the basis of determinant factors) had a better discriminative power than the IIL score. This system is useful for stratifying SMZL patients into risk groups and may help in the selection of risk-tailored treatment approaches.

Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin's lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL).

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.

Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after 90 Y-ibritumomab-tiuxetan.

Radioimmunotherapies with Zevalin® (RIT-Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure-free intervals longer than those achieved by the last previous therapy. We compared time-to-event variables obtained before and after RIT-Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non-transformed, non-refractory, non-rituximab-naïve FL who have been treated with RIT-Z in two different centres in Europe were included. Staging and response were assessed by contrast-enhanced CT in all patients; PET/CT was performed according to local availability. Event-free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT-Z were compared. Pre-therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo-immunotherapies, including a median of 2 rituximab-containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT-Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT-Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT-Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT-Z showed encouraging results in terms of prolonging EFS, warranting further studies.

18FDG-positron emission tomography in post treatment evaluation of residual mass in Hodgkin's lymphoma: long-term results.

In patients with Hodgkin's lymphoma (HL) at the end of first line therapy an accurate imaging technique with high prognostic value is needed to assess response to treatment and predict those patients who will suffer disease relapse. This technique and its results permit the quick initiation of a second line therapy in patients suffering from a progressive disease or those unresponsive to treatment avoid over-treatment of patients in complete remission or those having a non-active residual disease. We included a (18)FDG-positron emission tomography (PET) scan to the diagnostic set-up to investigate 28 patients following the end of their treatment. Fifteen patients out of the 28 (54%) had positive CT scans while 13 (46%) had negative ones. Eleven patients out of the 15 CT positive (73%) had negative PET scans and no relapse. The remaining four patients (27%) had positive PET scans with only one relapse (25%). With respect to the 13 patients who had negative CT scans, 9 patients (69%) had negative PET scans and no relapse. The remaining 4 patients (31%) had positive PET scans with 3 relapse cases (75%). In our final assessment after a median follow-up period of 45 months, starting from PET execution to the last follow-up, overall sensitivity of the CT and the PET were 25 and 100% respectively, specificity 42 and 83% respectively, positive predictive value (PPV) 7 and 50% respectively, negative predictive value (NPV) 77 and 100% respectively, and accuracy 39 and 86% respectively. In our experience, FDG-PET performed in patients after induction therapy appears to offer important additional information: FDG-PET results are predictors of prognosis giving 100% DFS in PET negative patients and 54% DSF in PET positive patients.

Quantification of dose nonuniformities by voxel-based dosimetry in patients receiving 90Y-ibritumomab-tiuxetan.

UNLABELLED: Abstract Objective: To assess the impact of nonuniform dose distribution within lesions and tumor-involved organs of patients receiving Zevalin(®), and to discuss possible implications of equivalent uniform biological effective doses (EU-BED) on treatment efficacy and toxicity. MATLAB™ -based software for voxel-based dosimetry was adopted for this purpose. METHODS: Eleven lesions from seven patients with either indolent or aggressive non-Hodgkin lymphoma were analyzed, along with four organs with disease. Absorbed doses were estimated by a direct integration of single-voxel kinetic data from serial tomographic images. After proper corrections, differential BED distributions and surviving cell fractions were estimated, allowing for the calculation of EU-BED. To quantify dose uniformity in each target area, a heterogeneity index was defined. RESULTS: Average doses were below those prescribed by conventional radiotherapy to eradicate lymphoma lesions. Dose heterogeneity and effect on tumor control varied among lesions, with no apparent relation to tumor mass. Although radiation doses to involved organs were safe, unexpected liver toxicity occurred in one patient who presented with a pattern of diffuse infiltration. CONCLUSION: Voxel-based dosimetry and radiobiologic modeling can be successfully applied to lesions and tumor-involved organs, representing a methodological advance over estimation of mean absorbed doses. However, effects on tumor control and organ toxicity still cannot be easily predicted.

Treatment of large cell lymphoma in elderly patients with a mitoxantrone, cyclophosphamide, etoposide, and prednisone regimen: long-term follow-up results.

BACKGROUND: Patients with aggressive non-Hodgkin lymphoma (NHL) require intensive and extensive therapy, which seems impracticable in elderly patients due to hematologic and extrahematologic toxicity. Consequent dose reduction and therapy attenuation can reduce treatment-related toxicity but also decreases therapeutic efficacy. Thus, age represents a fundamental prognostic factor that has a profound influence on both therapeutic decisions and patient outcome. METHODS: Between January, 1990 and June, 1997, 145 patients age > 64 years (median age, 72.3 years) with a diagnosis of aggressive NHL were treated on a chemotherapy regimen that consisted of mitoxantrone, cyclophosphamide, etoposide, and prednisone. RESULTS: Ninety-one patients (63%) achieved complete remission, and 48 patients (33%) achieved partial remission, for an overall response rate of 96%. Six patients (4%) were resistant to therapy. The overall survival rate, with a median follow-up of 66 months, was 44%, and the failure free survival rate was 42%. The disease free survival rate was 63.5%, with a median follow-up of 60 months. Multivariate survival analysis showed that the achievement of complete remission was the single most important prognostic factor, which was associated significantly with longer survival (P < 0.0001). Toxicity was moderate, with 5 deaths (3%) due to complications related to therapy. CONCLUSIONS: The current results confirm that a protocol devised specifically for elderly patients may reduce toxicity and allow longer overall survival in this particular subset of patients.

Análisis de la características de los donantes de sangre del Hospital Córdoba / Analysis of the characteristics of blood donors Hospital Córdoba

Los esfuerzos por aumentar la captación de donantes de sangre, deben basarse en un buen conocimiento de los datos epidemiológicos de cada población, las pautas de conducta de riesgo y la prevalencia de marcadores virales, sin embargo en Córdoba no existen antecedentes de investigaciones sobre las características de los donantes de sangre. Desde el descubrimiento del Virus del HIV, el proceso de selección de donantes de sangre ha mejorado, sin embargo sigue siendo considerado el aspecto más crítico en la confiabilidad de la sangre disponible para la transfusión de pacientes. Cuanto más baja sea la prevalencia de marcadores de enfermedades infectocontagiosas en la población de donantes, más bajo será el riesgo de transmisión de alguna de ellas, debido a la falta de sensibilidad en las pruebas de serología, la infectividad del “Período de Ventana”, o errores del personal. A partir del día 22 de Septiembre del año 2008, el Ministerio de Salud a través del Departamento del Sistema Provincial de Sangre ha puesto en marcha la centralización de todos los bancos de sangre estatales de la ciudad de Córdoba, lo cual permite contar con personal altamente especializado en la selección de donantes, con el fin de obtener sangre segura y solucionar la provisión de sangre de la ciudad en períodos de escasez, además de ayudar a que disminuya el descarte por vencimiento de unidades de grupos sanguíneos pocos frecuentes. El objetivo de esta investigación fue analizar las características de la población de donantes de sangre de un hospital de la ciudad de Córdoba y conocer los motivos más frecuentes por los cuales algunas personas eran diferidas para la donación. La investigación se realizó a partir de las declaraciones juradas de todas las personas que se presentaron a donar sangre durante el año 2007 en el Hospital Córdoba.

SUMMARY: Attempts to attract more blood donors should be based on a sound knowledge of the epidemiological data of the given population, its risk behavior patterns, and the prevalence of viral markers. So far, no record could be found in Córdoba of research on such characteristics of blood donors. Although the process of blood donor selection has improved since the discovery of the HIV virus, it continues to be the most critical factor in the reliability of the blood that is made available for transfusion to patients. A lower prevalence of markers of transmissible infectious diseases in the donor population will imply a lower transmission risk of said diseases that may result from: a lack of sensitivity of the screening tests, the risk of transmission during the “window period”, or human errors. Starting on September 22, 2008, the provincial Ministry of Health began the process of centralization of all state-run blood banks located in the city of Córdoba, implemented through the Provincial Blood Systems Department. This implies that the selection of donors is now in the hands of highly qualified personnel, aiming at the procurement of safe blood and at guaranteeing its provision to the city in times of shortage. Moreover, this helps to decrease the discarding due to expiration dates of the units corresponding to low-frequency blood types. The objective of this study is to analyze the characteristics of the donor population associated to a hospital located in Córdoba city and to find out the most frequent motives for donor rejection. The study is based on the sworn statements of all those persons who applied during 2007 to donate blood at the Hospital Córdoba.