Early progression as a predictor of survival in marginal zone lymphomas: An analysis from the FIL-NF10 study

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome inMZL and identifies a high-risk population

Pregnant women affected by thalassemia major: a controlled study of traits and personality

Background: The reproductive and sexual health issues concerning persons affected by thalassemia major are complex. The study was planned to investigate the psychological attitudes and expectations in a group of thalassemic pregnant women attending hospital for regular blood transfusion. Methods: This is a preliminary cross-sectional study involving 20 consecutive thalassemic patients and a control group of 42 healthy pregnant volunteers. The personality structure was evaluated by Rorschach's test and the presence of psychic symptoms by SCL-90-R and STAI. Results: Narcissism and sexual traumas are significantly higher in thalassemic women with respects to the control group. Also the percent of anxiety and depression observed with the SCL-90-R was significantly higher than in control group (45% vs. 3%, p < 0.001, mean and SD values are 1.65 \ub1 0.15 vs. 0.43 \ub1 0.18 for anxiety; 55% vs. 12%, p < 0.001, mean and SD values are 1.76 \ub1 0.18 vs. 0.85 \ub1 0.25 for depression). The score observed with the STAI shows that the trait of anxiety differed between thalassemic pregnant women and the control group, even though the score values aren't pathologic in neither group (87% vs. 42%, p < 0.05, mean and SD values are 33 \ub1 0.8 vs. 22 \ub1 0.2). Conclusions: This study addresses the need for developing, implementing and evaluating proper psychological support for thalassemic pregnant patients. Moreover, psychological screening and support prior to, during and following pregnancy would be indicated

PSYCHOLOGICAL EVALUATION IN PREGNANT WOMEN AFFECTED BY THALASSEMIA MAJOR: TRAITS AND PERSONALITY

Background. The reproductive and sexual health issues concerning persons affected by thalassemia major are complex. The study was planned to investigate the psychological attitudes and expectations in a group of thalassemic pregnant women attending hospital for regular blood transfusion.&#13; Methods. The study included 20 consecutive thalassemic patients and a control group of 42 healthy pregnant volunteers. We evaluated the personality structure by Rorschach's test and the presence of psychic symptoms by SCL-90-R and STAI. &#13; Results. Narcissism and sexual traumas are significantly higher in thalassemic women with respects to the control group. Also the percent of anxiety and depression observed with the SCL-90-R was significantly higher than in control group. The score observed with the STAI shows that the state of anxiety changed significantly between thalassemic pregnant women and the control group, even though the scores values aren’t pathologic in neither group.&#13; Conclusions. This study addresses the need for developing, implementing and evaluating proper psychological support for thalassemic pregnant patients. The limit of this study is to analyze just thalassemic women because it doesn’t consider other pathologies; so the results can’t be extended to other pathologies different from thalassemic. Moreover, psychological screening and support prior to, during and following pregnancy would be indicated. Since not there are psychological studies in literature on the pregnancy in the thalassemic patients, the evaluation of the effects of pregnancy on the thalassemic disease will be the aim of future psychological investigations

A Phase II study of Bendamustine in Combination With Rituximab as Initial Treatment for Patients With Indolent non-follicular non-Hodgkin's Lymphoma

The purpose of this phase 2 study was to determine the activity and safety of 6 cycles of bendamustine and 8 rituximab (RB) as first-line treatment of adult patients with advanced stage non-follicular indolent non-Hodgkin lymphomas (INFL). The primary endpoint was the complete response rate (CRR) with expected CRR of 75%. Sixty-nine patients were enrolled; median age was 65 years (45-75), 65% were male, 93% of patients had stage IV disease. Complete and overall response rates were 48% (95% IC 35.6-60.2), and 86% (IC 75.0-92.8). The most common grade 3/4 adverse events were neutropenia (43%), thrombocytopenia (7%), anemia (4%); whereas the rate of febrile neutropenia was very low (3%). At a median follow up of 22 months (1-43 months), 2-year progression free survival was 89% (IC: 79-95), and 2-year overall survival was 96% (IC: 87-99). RB combination is active and well tolerated in patients with advanced stage previously untreated INFL

Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study

Rituximab (®) provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade ≥ 3 neutropenia: 26%; grade ≥ 3 infections: 8%). Of the 15 deaths, two occurred on treatment (one sepsis and one pneumonia). Six deaths were due to lymphoma progression, four to secondary neoplasia, one to sepsis, one to pneumonia and one to splenectomy complications. R-COMP should be restricted to patients with bulky disease associated with symptoms or to patients with possible histological transformation

Risk factors for impaired gonadal function in female Hodgkin lymphoma survivors: final analysis of a retrospective multicenter joint study from Italian and Brazilian Institutions.

Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors

Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: the FIL_ReRi Phase 2 Study

: Treatment of diffuse large B-cell lymphoma (DLBCL) in elderly patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. The Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a two-stage single arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2)in ≥ 70-year-old untreated frail DLBCL patients. Frailty was prospectively defined according to a simplified geriatric assessment tool. Patients were given a maximum of 6 28-day cycles of 20 mg oral lenalidomide on days 2-22 and intravenous rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients in partial (PR) or complete response (CR) at cycle 6 were given lenalidomide 10 mg/d on days 1-21 in q28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) after cycle 6; the co-primary endpoint was the rate of grade 3-4 extra-hematological toxicity. The ORR was 50.8%, with 27.7% of CR. After a median follow-up of 24 months, median progression-free survival (PFS) was 14 months, and two-year duration of response was 64%. Thirty-four patients experienced extra-hematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3. Activity of R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach of elderly frail patients with DLBCL. The trial was registered at ClinicalTrials.gov as NCT01805557

Safety and efficacy of lenalidomide in combination with rituximab in recurrent indolent non-follicular lymphoma: final results of a phase II study conducted by the Fondazione Italiana Linfomi

We present the final results of a Phase II study that evaluated safety and efficacy of lenalidomide in combination with rituximab in 39 patients with recurrent small lymphocytic lymphoma (N=18), marginal zone lymphoma (N=8), or lymphoplasmacytic lymphoma (N=13). Patients received oral doses of lenalidomide 20 mg once daily on days 1-21 and rituximab 375 mg/m2 on day 14 of each 28-day course. Patients received up to 6 courses. The overall response was 54%, with a complete response of 21%. At 2 years, progression free survival, duration of remission, and overall survival were 45%, 76%, and 78%, respectively. The evaluation of treatment response by histology showed an overall response rates of 75%, 46%, and 50%, in marginal zone, lymphoplasmacytic and small lymphocytic lymphoma, respectively. Histology-based estimates of remission durations at 2 years were 100%, 100%, and 51% for marginal zone, lymphoplasmacytic, and small lymphocytic lymphomas, respectively. A log rank test showed that the marginal zone and lymphoplasmacytic lymphoma curves were marginally significantly different from the small lymphocytic lymphoma curve. Our results demonstrated that patients with recurrent marginal zone and lymphoplasmacytic lymphomas that responded to the combination treatment had long-lasting responses. Of note, no other studies have published the effects of this combination treatment on patients with relapsed lymphoplasmacytic lymphoma. Our findings showed a mild, predictable, and manageable toxicity profile. Confirmation of these results in Phase III trials will facilitate moving towards a chemotherapy-free approach in the management of indolent non-Hodgkin lymphoma. ClinicalTrials.gov; Identifier: NCT01830478