The prognostic role of post-induction FDG-PET in patients with follicular lymphoma: a subset analysis from the FOLL05 trial of the Fondazione Italiana Linfomi (FIL).

BACKGROUND: [18F]fluorodeoxyglucose-positron emission tomography (PET) is emerging as a strong diagnostic and prognostic tool in follicular lymphoma (FL) patients. PATIENTS AND METHODS: In a subset analysis of the FOLL05 trial (NCT00774826), we investigated the prognostic role of post-induction PET (PI-PET) scan. Patients were eligible to this study if they had a PI-PET scan carried out within 3 months from the end of induction immunochemotherapy. Progression-free survival (PFS) was the primary study end point. RESULTS: A total of 202 patients were eligible and analysed for this study. The median age was 55 years (range 33-75). Overall, PI-PET was defined as positive in 49 (24%) patients. Conventional response assessment with CT scan was substantially modified by PET: 15% (22/145) of patients considered as having a complete response (CR) after CT were considered as having partial response (PR) after PI-PET and 53% (30/57) patients considered as having a PR after CT were considered as a CR after PI-PET. With a median follow-up of 34 months, the 3-year PFS was 66% and 35%, respectively, for patients with negative and positive PI-PET (P<0.001). At multivariate analysis, PI-PET (hazard ratio 2.57, 95% confidence interval 1.52-4.34, P<0.001) was independent of conventional response, FLIPI and treatment arm. Also, the prognostic role of PI-PET was maintained within each FLIPI risk group. CONCLUSIONS: In FL patients, PI-PET substantially modifies response assessment and is strongly predictive for the risk of progression. PET should be considered in further updates of response criteria.

The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi.

BACKGROUND: The role of [¹8F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) in follicular lymphoma (FL) staging is not yet determined. PATIENTS AND METHODS: The aim of the present study was to investigate the role of PET in the initial staging of FL patients enrolled in the FOLL05-phase-III trial that compared first-line regimens (R-CVP, R-CHOP and R-FM). Patients should have undergone conventional staging and have available PET baseline to be included. RESULTS: A total of 142 patients were analysed. PET identified a higher number of nodal areas in 32% (46 of 142) of patients and more extranodal (EN) sites than computed tomography (CT) scan. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score increased in 18% (26 of 142) and decreased in 6% (9 of 142) of patients. Overall, the impact of PET on modifying the stage was highest in patients with limited stage. Actually, 62% (15 of 24) of cases with limited disease were upstaged with PET. CONCLUSIONS: The inclusion of PET among staging procedures makes the evaluation of patients with FL more accurate and has the potential to modify therapy decision and prognosis in a moderate proportion of patients. Further prospective clinical trials on FL should incorporate PET at different moments, and the therapeutic criteria to start therapy should be re-visited in the views of this new tool.

Association of social network and social support with health-related quality of life and fatigue in long-term survivors of Hodgkin lymphoma.

PURPOSE: As the number of survivors of Hodgkin's lymphoma (HL) increases, there has been a growing interest in long-term treatment-related side effects and their impact on the quality of life (QoL). The aim of this study was to assess the association of social network and social support with the QoL and fatigue among long-term HL survivors. METHODS: A total of 200 HL survivors were included. The generic Short Form-12 (SF-12) questionnaire, the QoL cancer survivor's questionnaire (QOL-CS), and the Multidimensional Fatigue Inventory were used to assess QoL and fatigue. Social network and social support were evaluated with the Social Support Survey. RESULTS: Social network and all social support measures were favorably associated with two or more SF-12 scales, mainly with physical functioning and the mental health scales. Social network and social support dimensions were also associated with better QOL-CS scores. Affective support, informational support, positive interaction, and emotional support were associated with less fatigue. CONCLUSIONS: Both social network and social support are associated with better QoL and lower levels of fatigue in HL survivors. This information may be useful to health professionals and community organizations in implementing effective interventions to improve these patients' quality of life.

Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma.

BACKGROUND: A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkin's lymphoma (cHL). PATIENTS AND METHODS: The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS: There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION: CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

Analysis of factors influencing inclusion of 102 patients with stage III/IV Hodgkin's lymphoma in a randomized trial for first-line chemotherapy.

BACKGROUND: Data on factors influencing inclusion of Hodgkin's lymphoma (HL) patients in randomized clinical trials (RCT) are limited and, for the present study they were analyzed in a RCT for III/IV HL. PATIENTS AND METHODS: All patients with stage III/IV HL referred to the Saint-Louis Hospital between January 2003 and May 2007 were studied. A Groupe d'Etudes des Lymphomes de l'Adulte/European Organisation for Research and Treatment of Cancer RCT, to compare ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with increased-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), was open for recruitment. Noninclusion criteria and physician's reasons for non-recruitment were prospectively recorded. The reasons for patient's refusal were collected retrospectively. Logistic regression analyses were carried out in order to identify factors predicting inclusion. RESULTS: A total of 102 patients were diagnosed, among whom 51% were included. Seven patients were ineligible, 22 refused to participate, and 21 were not enrolled due to the physician's decision. Main reasons for patients' refusal were standard treatment preference and concerns about experimental arm toxicity, mainly infertility risk. Conditions that could hamper accurate follow-up and toxicity concerns accounted for most of the physicians' reasons. Adverse prognostic factors [B symptoms (odds ratio, OR = 5.35) and international prognostic score > or =3 (OR = 2.69)] were independently associated with inclusion. CONCLUSION: Despite an attractive protocol, only 51% of patients were included. It highlights concerns about selection of patients and the difficulty to obtain informed consent with better prognostic profile patients.

CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk-adaptive strategies. METHODS AND RESULTS: Bcl-2 and CD10 expression was determined by immunohistochemistry. The impact of the positivity on survival was evaluated in combination with the IPI in 86 patients with a confirmed diagnosis of DLBCL. Patients were divided according to the IPI into low-risk (no to two factors) or high-risk (three to five factors) groups. Positivity rates were 25% for CD10 and 42% for Bcl-2. In a Cox analysis, the high-risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl-2 expression (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the low-risk IPI group, CD10 positivity was associated with an excellent 8-year overall survival (92% versus 45%, P = 0.06). In the high-risk IPI group, Bcl-2 positivity identified a subgroup with invariably fatal disease. CONCLUSIONS: The expression of CD10 in the low-risk IPI group, and the expression of Bcl-2 in the high-risk IPI group can identify two subgroups of patients who might benefit from new risk-adaptive treatment approaches.

Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria.

Engraftment syndrome (ES) is an increasingly reported complication of hematopoietic stem cell transplantation (HSCT). In order to better characterize the clinical criteria for the diagnosis of ES, we retrospectively analyzed 125 autologous HSCT recipients. ES was first defined as the presence of noninfectious fever plus skin rash. Patients with and without these findings were compared (univariate and multivariate analyses) regarding the presence of weight gain, hypoalbuminemia, pulmonary infiltrates, diarrhea, neurological manifestations and jaundice. The variables that are significantly more frequent in patients with fever and skin rash were incorporated in the definition criteria. The final diagnostic criteria were noninfectious fever plus any of the following: skin rash, pulmonary infiltrates or diarrhea. The incidence of ES was 20%. The single risk factor for ES by multivariate analysis was a diagnosis other than Hodgkin's disease (odds ratio 6.17, 95% confidence interval 1.38-27.78). Patients with ES received empirical antifungal therapy more frequently than patients without the syndrome (40 vs 19%, P=0.03), and had a longer duration of hospitalization (P=0.0007). The prospective application of these diagnostic criteria may have a favorable impact on the early diagnosis of the syndrome, with the initiation of corticosteroids and a reduction in the unnecessary use of antimicrobial agents.

Application of an adapted international prognostic index for aggressive non-Hodgkin's lymphomas: good discrimination and lower survival rates in Rio de Janeiro, Brazil.

Institutions that treat patients with lymphoma must know their local therapy results and adapt their treatment strategies accordingly. To allow the application of the international prognostic factor index (IPI) in institutions where some of the data necessary are not available, we devised an approach by which the missing data would not impair the applicability of the index. We also collapsed the four categories of the IPI into two categories, and applied this adapted IPI to patients with aggressive non-Hodgkin's lymphoma treated in a public university hospital. Among the 72 patients treated with combination chemotherapy regimens containing doxorubicin, the following outcomes were observed for low and high risk groups, respectively: complete remission rates were 62% and 45% (p=0.2), overall survival rates were 48% and 14% (p=0.0098) and failure-free survival rates were 44% and 17% (p=0.03). This adapted IPI was very effective in predicting the outcome in the patients studied. The survival rates observed in our population were substantially lower than the rates reported in the IPI study. Patient selection might have played an important role in this difference, although other factors related to the social and general health status of the patients treated need to be prospectively studied.

A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients.

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Predictive value of a positive nasal swab for Aspergillus sp. in the diagnosis of invasive aspergillosis in adult neutropenic cancer patients.

To evaluate the value of a positive nasal swab for Aspergillus in the diagnosis of invasive aspergillosis, we prospectively evaluated nasal colonization in 173 episodes of neutropenia in 92 patients with hematological malignancies. Weekly nasal swabs were taken, and the patients were followed until death or resolution of neutropenia. The outcome variables were the development of invasive aspergillosis, empirical antifungal therapy and death. In 31 episodes of neutropenia (18%) there was at least one positive nasal swab for Aspergillus sp. Only two patients developed invasive aspergillosis, both with a positive nasal swab (p = 0.03). The positive and negative predictive values of a nasal swab were 6.4% and 100%, respectively. There was no difference between patients with positive or negative swabs regarding antifungal therapy or death. In this population of patients, a nasal swab for Aspergillus sp. had a low positive predictive value and a high negative predictive value for invasive aspergillosis.

Ceftazidime plus amikacin plus teicoplanin or vancomycin in the empirical antibiotic therapy in febrile neutropenic cancer patients.

A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.

Risk factors for typhlitis.

A case-control study was undertaken to identify risk factors for typhlitis in patients with hematological malignancies. A data base file with a total of 410 episodes of fever and neutropenia in patients cared for between May 1987 and 1996 was reviewed. Typhlitis was defined as a symptom complex of fever, intense abdominal pain and tenderness in the presence of neutropenia. Five cases of typhlitis were identified. Three controls for every patient were randomly selected from the same cohort. Diarrhea and jaundice were more frequent in patients than in controls (p=0.03). The presence of mucositis, prolonged duration of profound neutropenia and idarubicin treatment proved to be risk factors for typhlitis.