Rituximab maintenance after autologous stem cell transplantation prolongs response duration in non-naive rituximab follicular lymphoma patients: a single institution experience.

We retrospectively evaluated the role of rituximab (R) in maintenance treatment after autologous stem cell transplantation performed in patients with relapsed follicular lymphoma. We compared the outcome of 67 follicular lymphoma (FL) patients according to the use of rituximab maintenance (RM) or not. All patients received rituximab plus chemotherapy before autologous stem-cell transplantation (ASCT). Patients received median of two lines of prior therapy. The RM schedule was one injection of rituximab every 3 months for 2 years. Median follow-up is 4.6 years. The 3-year progression-free survival (PFS) after ASCT was 86 % with RM vs. 46 % without (p = 0.0045). Median is not reached in the RM arm vs. 31 months in non-RM arm. The 3-year OS was 96 % with RM vs. 78 % without (p = 0.059). The present monocentric study shows that 2 years of RM after ASCT significantly increases response duration for non-naive rituximab relapsed FL patients compared with observation.

Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC.

Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.

Venous thromboembolism related to warm autoimmune hemolytic anemia: a case-control study.

BACKGROUND: The risk of venous thromboembolism (VTE) during warm autoimmune hemolytic anemia (wAIHA) is apparent in several published series. Unlike proximate disorders (autoimmune thrombocytopenia, non-immune hemolytic diseases) little is known about the presentation and risk factors for VTE in this setting. OBJECTIVE: To determine the frequency, presentation and risk factors for VTE associated with wAIHA. METHODS: We performed a single center retrospective study of adult patients (>18years) followed for wAIHA between 2009 and 2013. VTE risk factors were systematically assessed. The characteristics of patients with or without VTE were compared. VTE presentation and precipitating factors were analyzed. The Padua VTE risk score was calculated in each case. RESULTS: Forty patients were included. wAIHA was idiopathic in 24 patients (60%). Twelve patients (30%) had Evans syndrome. Mean lowest hemoglobin level was 6.6g/dl [3.7-11.5]. Eight patients (20%) presented VTE after the appearance of wAIHA, at a mean age of 52.5years. All patients had pulmonary embolus, associated with a deep venous thrombosis in 4 cases. At the time of VTE 7/8 patients had frank hemolysis (median hemoglobin level: 7g/dL) and 6/8 were outpatients with a low Padua VTE risk score. The frequency of usual VTE risk factor was similar in cases and controls. By contrast, lowest hemoglobin level was significantly lower in patients that experienced VTE (5.3 vs 7.2g/dL, p=0.016). During the first episode of wAIHA, patients with concurrent VTE had a more pronounced anemia (5.3 vs 7.4g/dL, p=0.026). At the time of VTE, anemia was more severe when no other precipitating factor was present (6 vs 8.9g.dL, p=0.04). CONCLUSION: In our cohort, 20% of patients with wAIHA presented VTE. The vast majority of VTE occurred during severe hemolytic flares and were not attributable to usual VTE risk factors. VTE prophylaxis is advisable in any patient admitted for wAIHA, irrespective of Padua VTE risk score. Prophylaxis also seems reasonable for outpatients with marked hemolysis.

Upfront allogeneic stem-cell transplantation for patients with nonlocalized untreated peripheral T-cell lymphoma: an intention-to-treat analysis from a single center.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases with dismal outcome when treated with chemotherapy alone. Because allogeneic stem-cell transplantation (allo-SCT) can cure relapse/refractory patients, we hypothesized that upfront allo-SCT may provide a better outcome. Therefore, all patients that presented with advanced PTCL in our institution at diagnosis were scheduled to undergo upfront allo-SCT after induction chemotherapy. PATIENTS AND METHODS: The aim of the present work was to assess the feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly diagnosed PTCL patients were scheduled to receive upfront allo-SCT. A human leukocyte antigen-matched donor was found for 42 patients: related to the patient in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in 7 cases. RESULTS: After induction chemotherapy, 17 patients reached complete remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the 1 and 2-year overall survival (OS) rates were 59% [95% confidence interval (CI) 47-75] and 55% (95% CI 43-71), respectively. The most frequent reason we did not proceed to allo-SCT was disease progression or insufficient response after induction. For transplanted patients, the 1- and 2-year OS were 76% (95% CI 62-93) and 72.5% (95% CI 58-91), respectively. Toxicity-related mortality (TRM) 1 year after allo-SCT was only 8.2% (95% CI 0-18.5). The 2-year progression-free survival (PFS) rate of patients who did not proceed to allo-SCT (n = 20) was below 30%. The disease status at the time of transplantation was a strong predictive marker for both PFS and OS in transplant patients. CONCLUSIONS: Upfront allo-SCT in PTCLs is feasible with low TRM, and it provides long-term disease control. However, one-third of patients remain chemo-refractory and, thus, new therapeutic approaches are warranted. The role of upfront allo-SCT compared with other therapeutic approaches in PTCLs requires investigation in randomized studies.

Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience.

IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4-128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.

Waiting time disparities in breast cancer diagnosis and treatment: a population-based study in France.

Waiting times are key indicators of a health's system performance, but are not routinely available in France. We studied waiting times for diagnosis and treatment according to patients' characteristics, tumours' characteristics and medical management options in a sample of 1494 breast cancers recorded in population-based registries. The median waiting time from the first imaging detection to the treatment initiation was 34 days. Older age, co-morbidity, smaller size of tumour, detection by organised screening, biopsy, increasing number of specimens removed, multidisciplinary consulting meetings and surgery as initial treatment were related to increased waiting times in multivariate models. Many of these factors were related to good practices guidelines. However, the strong influence of organised screening programme and the disparity of waiting times according to geographical areas were of concern. Better scheduling of diagnostic tests and treatment propositions should improve waiting times in the management of breast cancer in France.

[Acquired hemophilia A. A monocentric retrospective study of 39 patients]. / Hémophilie A acquise. Étude d'une série rétrospective monocentrique de 39 patients.

PURPOSE: Acquired haemophilia A (AHA) is a rare bleeding disorder, due to the presence of an inhibitor directed against factor VIII (FVIII). About 50% of the AHA are idiopathic, while the remaining 50% are related to an underlying disorder or condition (autoimmune diseases, malignancies, postpartum, etc.). PATIENTS AND METHODS: We report on a monocentric retrospective cohort of 39 patients with AHA. Data were collected and compared to recent published data. RESULTS: Thirty-nine patients were admitted for AHA between 1993 et 2011. Mean age at diagnosis was 71.3 years, and we noted a marked male predominance. Although the majority of patients presented a bleeding event at diagnosis (94.9%), the hemorrhagic mortality was low (2.6%). On the contrary, immunosuppressive morbidity and mortality were high in this elderly population. There was a clear correlation between initial FVIII inhibitor titer and complete remission delay. We did not identify prognostic factor for global survival. CONCLUSION: AHA is a rare but potentially fatal disorder. Rapidity of diagnosis and treatment initiation is crucial. Morbidity and mortality, particularly of infectious cause, due to immunosuppressive treatment, should lead to consider other available therapeutical options.

Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience.

BACKGROUND: Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy. PATIENTS AND METHODS: We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers. RESULTS: Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS. CONCLUSIONS: These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen.

Topical corticosteroid phobia in atopic dermatitis: a study of its nature, origins and frequency.

BACKGROUND: Topical corticosteroids remain the mainstay of atopic dermatitis therapy. Many atopic dermatitis therapeutic failures appear to be attributable to poor adherence to treatment due to topical corticosteroid phobia. OBJECTIVES: To assess the facets, origins and frequency of fear of topical corticosteroid use among patients with atopic dermatitis. METHODS: A questionnaire comprising 69 items, generated from information gathered during interviews with 21 patients and 15 health professionals, was given to consecutive patients consulting at the outpatient dermatology departments of five regional university hospitals or with 53 dermatologists in private practice. RESULTS: A total of 208 questionnaires were analysed (including 144 from parents and 87 from adult patients, 27 of whom were also parents); 80·7% of the respondents reported having fears about topical corticosteroids and 36% admitted nonadherence to treatment. A correlation was found between topical corticosteroid phobia and the need for reassurance, the belief that topical corticosteroids pass through the skin into the bloodstream, a prior adverse event, inconsistent information about the quantity of cream to apply, a desire to self-treat for the shortest time possible or poor treatment adherence. Topical corticosteroid phobia was not correlated with atopic dermatitis severity. CONCLUSION: Topical corticosteroid phobia is a genuine and complex phenomenon, common among French patients with atopic dermatitis, that has an important impact on treatment compliance.

Incidentally-discovered gallbladder cancer: When, why and which reoperation?

Cancer of the gallbladder, a rare entity with a poor prognosis, is often discovered incidentally during or after cholecystectomy. It tends to disseminate early via lymphatic, peritoneal, endobiliary, and hematogenous pathways. Diagnosis is made intra-operatively in only a quarter of cases, by examination of the opened cholecystectomy specimen in the operating room by the surgeon; this procedure should be routine. For incidentally-discovered cancers, survival was 28% at five years. Prognostic factors include age, TNM stage, gallbladder perforation during cholecystectomy and less-than-optimal resection at re-operation. Whether the laparoscopic route for the initial cholecystectomy has an impact on survival remains a subject of debate. R0 surgery is the only potentially curative treatment: simple cholecystectomy with clear margins is adequate resection for stage T1a tumors; extended cholecystectomy with lymphadenectomy and possibly resection of the bile duct is required for more advanced stages. After curative resection, neo-adjuvant or adjuvant chemotherapy and radiotherapy have not, so far, proven effective. Improvement of surgical practices (systematic review of cholecystectomy specimens in the OR, prevention of gallbladder perforation with bile spillage during surgery, early re-intervention for optimal resection) could improve the prognosis of these cancers.

Risk factors of thyroid tumors: role of environmental and occupational exposures to chemical pollutants.

BACKGROUND: The rising incidence of thyroid cancer observed during the last few decades in most western countries is explained in large part by increasing numbers of diagnoses due to changes in medical screening practices. However, beside radiation exposure, exposure to environmental chemicals may also play a role in thyroid cancer etiology and in the increased incidence. This paper presents the main chemicals suspected to induce thyroid tumorigenesis, and epidemiological results on the association between chemical exposure and thyroid tumors. METHODS: We reviewed experimental studies to identify the main chemicals possibly involved in thyroid tumorigenesis. We also reviewed the main epidemiological studies investigating the association between environmental chemical exposure and thyroid neoplasm in humans. RESULTS: Environmentally abundant chemicals may disrupt thyroid function and/or play a role in tumorigenesis through a variety of mechanisms. Epidemiological results provide insufficient evidence of a causal link between exposure to environmental chemicals and thyroid tumors, but raise the hypothesis of an increased risk of thyroid neoplasm for workers in the leather, wood, and paper industries, and those exposed to certain solvents and pesticides. CONCLUSION: This paper highlights the need for large epidemiological studies evaluating the exposure to various groups of environmental chemicals and its impact on the thyroid gland.

Recent trends in breast cancer incidence rates in the Loire-Atlantique, France: a decline since 2003.

BACKGROUND: A recent decline in breast cancer incidence rates has been reported in the United States and in Europe. This decrease has been partly attributed to the reduced use of hormone replacement therapy (HRT). No study in Europe has detailed recent breast cancer incidence trends both by hormonal receptor status and mode of detection at an individual level. METHODS: We examined trends in breast cancer incidence rates in the French administrative area of Loire-Atlantique between 1991 and 2007, by age, mode of detection, histological subtype, estrogen/progesterone receptor (ER/PR) status and grade. Annual age-standardized breast cancer incidence rates were estimated using the Loire-Atlantique and Vendée Cancer Registry data. Annual percentage changes (APCs) were estimated using an age-adjusted Poisson regression model. RESULTS: Incidence rates of breast cancer increased 3.5% per year in 1991-2003, dropped -4.3% per year in 2003-2006 and increased in 2007 (9.1%). Stratified analyses by age groups showed that the decrease concerned predominantly women aged 50-64 years, whereas an increasing proportion of cancers detected by organized screening was observed in this age group. Among these women, the decline of incidence particularly concerned positive estrogen and progesterone receptor tumors, lobular subtype tumors, and low-grade tumors. CONCLUSION: The drop in breast cancer incidence rates observed between 2003 and 2006 in women 50-64 years old was greater for ER+PR+ tumors. During the same period, the incidence of breast cancers diagnosed by organized screening increased. These patterns appear consistent with an impact of the reduced use of HRT.

[Time trends in the geographic variation of thyroid cancer incidence by tumor size from 1983 to 2000 in France]. / Disparités géographiques d'évolution d'incidence des cancers de la thyroïde par taille entre 1983 et 2000 en France.

BACKGROUND: The aim of this investigation was to study geographic time trends of thyroid cancer incidence according to tumor size in France, 1983 to 2000. METHODS: Incidence data were provided from six French registries over the period 1983-2000 covering seven administrative districts. Five tumor size groups were distinguished: < 10mm, 10-20mm, 20-40mm, > 40mm and unknown size. Papillary cancers diagnosed in women were analyzed according to tumor size in each geographic area. World age standardized rates were calculated and annual percent change rates were estimated for each tumor size group in each geographic area. Loglinear Poisson regression models were used to study geographic discrepancies in time trends incidences. RESULTS: The six French registries included 2222 papillary thyroid cancers in women between 1983 et 2000. Thyroid cancer incidence was increasing in the six geographic areas. Geographical variations in time trends incidence between registries reflected geographical variations in time trends incidence of small sized tumors (less than 10mm). CONCLUSION: Wide geographic variations in thyroid cancer incidence were noticed for small size tumors, which may be correlated with geographic variations in medical practices.