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.

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.

[Proteomics, a new tool for an accurate typing of amyloidosis]. / La protéomique, une nouvelle technique pour un typage optimal des amyloses.

Amyloidosis is a rare group of diseases related to extracellular deposition of proteins in an insoluble beta-pleated sheet structure presenting a characteristic apple-green birefringence under polarized light after Congo red staining. Thirty types of proteins are known to cause amyloidosis. The accurate identification of the amyloid protein is of paramount importance since it is a key step for the clinical management and personalized treatment. Amyloid typing is usually based on immunohistochemistry and immunofluorescence on tissular sections. This approach has several limits leading to a subtyping failure rate of 15 to 58% of cases. To overcome these difficulties, proteomic methods have been developed to characterize directly the amyloid protein. The most advanced technique carried out on fixed and paraffin-embedded tissue consists of laser microdissection followed by mass spectrometry. The type of amyloidosis can be determined in more than 95% of cases. However, the experience for this technique is very limited apart from the Mayo Clinic (Rochester, United States). In France, a very close proteomic assay has been implemented in the department of pathology of Foch Hospital with similar results. The introduction of proteomics in clinical practice represents a major improvement for typing amyloidosis. In this article, we discuss the benefits and limits of the different techniques used for amyloid classification and we briefly report our proteomic results.

Autologous transplantation in CLL patients with B and C Binet stages: final results of the prospective randomized GOELAMS LLC 98 trial.

The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to compare two strategies in previously untreated CLL patients aged <60 years. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP followed by six CHOP courses in every 3 months in those achieving a complete or PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as consolidation after three CHOP courses in case of CR or very good PR. A total of 86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates that frontline high-dose therapy with auto-SCT prolongs PFS but does not translate into a survival advantage in advanced CLL patients in the pre-rituximab era.

Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS.

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.

18F-fluorodeoxyglucose-positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group.

BACKGROUND: In non-cutaneous T-cell/natural killer (T/NK) lymphomas, the prognostic value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during or after therapy is unknown. PATIENTS AND METHODS: In this retrospective study, 54 T/NK lymphoma patients were assessed using FDG-PET before (n = 40), during (n = 44) and/or after therapy (n = 31). RESULTS: FDG-PET showed an abnormal FDG uptake in all cases. Interim FDG-PET was negative in 25 of 44 cases. After completion of therapy, 19 of 31 patients reached complete remission with negative FDG-PET. In ALK+ anaplastic large cell lymphomas, the 4-year progression-free survival (PFS) was 80% and the negative predictive value of post-therapy FDG-PET was 83% (n = 9). In ALK- T/NK lymphomas, the 4-year PFS was 59% for patients with a negative interim FDG-PET versus 46% for patients with a positive interim FDG-PET (P = 0.28, n = 35). Similarly, there was no statistical difference in 4-year PFS between negative and positive post-therapy FDG-PET in these lymphomas (51% and 67%, respectively, P = 0.96). The 4-year cumulative incidence of relapse from a negative post-therapy FDG-PET was 53% in ALK- T/NK lymphomas. CONCLUSIONS: Although T/NK lymphomas are FDG-avid at diagnosis, a negative interim or post-therapy FDG-PET does not translate into an improved PFS in ALK- T/NK lymphomas.

Impact of high-dose chemotherapy followed by auto-SCT for positive interim [18F] FDG-PET diffuse large B-cell lymphoma patients.

[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is increasingly used for response assessment in diffuse large B-cell lymphoma (DLBCL). A positive interim FDG-PET was shown to be associated with an unfavorable outcome in high-grade non-Hodgkin's lymphomas. For positive interim FDG-PET patients, the question of increasing the intensity of treatment using high-dose chemotherapy followed by auto-SCT (HDC-ASCT) remains unanswered. We retrospectively analyzed the prognostic value of FDG-PET in 42 DLBCL patients who were systematically evaluated at time of diagnosis, before and after HDC-ASCT. Of note, HDC-ASCT was part of the initial treatment strategy, while FDG-PET results did not influence the treatment approach. Results and outcome were analyzed according to FDG-PET results before and after HDC-ASCT. Patients were classified into three groups according to FDG-PET results before and after HDC-ASCT: those who were negative before and after (-/-; n=25), positive before and negative after (+/-; n=9) or positive before and after (+/+; n=8). The median follow-up was 34.5 (range, 19-74) months. The median EFS was significantly lower for the +/+ group (27.4 months) as compared with other groups (median not reached; P=0.0001). More importantly, there was no difference in term of EFS between the -/- group compared with the +/- group. These results suggest that HDC-ASCT can significantly improve the bad prognosis, otherwise indicated by a positive interim FDG-PET.

Large granular lymphocyte leukemia with pure red cell aplasia associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: an unfortuitous association?

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a recessively inherited monogenic disease caused by a mutation in the autoimmune regulator (AIRE) gene. AIRE plays a major role in central (thymic) immune tolerance. In the absence of AIRE, autoimmunity develops that is especially targeted at endocrine tissues. T-cell large granular lymphocyte (T-LGL) leukemia is a monoclonal lymphoproliferative disease characterized by persistent and indolent lymphocytosis. Autoimmune manifestations, such as rheumatoid arthritis or autoimmune cytopenia, are also common. We report the case of a patient with APECED, who presented with pure red cell aplasia associated with T-LGL leukemia. The association of T-LGL leukemia and APECED is very rare and may not be fortuitous. The immunological mechanisms of this association are discussed.

[Improving medical information for patients with a customized website]. / Amélioration de l'information médicale des patients: intérêt pour un service d'ophtalmologie de disposer d'un site Internet.

INTRODUCTION: In order to improve medical information for the patients consulting at the Department of Ophthalmology, an Internet website was set up. We wanted to estimate the rate of patients connecting to this website. Then we evaluated how the patients could draw a benefit from visiting this Internet site. PATIENTS AND METHODS: Prospective study of the patients seen in the department of ophthalmology over 4 consecutive days in May 2007. The first questionnaire was distributed to all patients and completed in the department. The second one was given only to the patients equipped with a broadband Internet connection and was to be completed at home after having visited the website. RESULTS: Six hundred twenty-one patients were admitted to the department during the period; 510 (82%) were included in the study. Among them, 382 (74.9%) responded to the first questionnaire. The broadband connection rate was 42.5%, 74.5% of these patients took an interest in our site, and 64.6% thought of visiting it. Forty-two (29%) responded to the second questionnaire. After having visited the site, 61.2% of the patients felt that their medical information was improved, 71.8% rated the quality of the site as good, and 87.9% would recommend this site to their relatives. CONCLUSION: This type of website is liable to efficiently supplement the information provided by the Ophthalmology Department doctors. It justifies the time and staff investment necessary for its operation.

Website navigation and surgical education.

We evaluated the way in which medical students interacted with a surgical education Website. Ten medical students on their paediatric surgery rotation were asked to study online a chapter on intussusception in young children, for a period of 1 h. The computer was connected by video link to a video-recorder that recorded their navigation movements, i.e. navigation time, time spent in front of each page, stepwise, progressive exploration of the surgical contents, and use of interactive links. The students were asked to complete a questionnaire to identify their overall competency in computers and Internet navigation capabilities. The mean time spent viewing the entire Website was 48 min (range 31-63) and the mean time spent on the assigned chapter was 38 min (range 8-53). Each page out of 14 within the chapter was visited a mean of 1.8 times (range 0-10). Access to video selections occurred after a mean of 10 min after beginning the session. A connection was made to the video a mean of 2.3 times per session. The mean time spent viewing video footage was 9 min (24% of the time spent viewing the chapter). The questionnaire results showed that few students regularly accessed the Internet for educational purposes.

Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma.

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.

Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.

[WebSurg and the Virtual University]. / WebSurg si universitatea virtuala.

Multimedia medical education has been demonstrated to be effective, and in some situations, superior to traditional methods of instruction, surgeons being able to acquire new skills from a distance. The purpose of this project was to develop an instructional aid that can be used for surgical education in laparoscopic techniques. A concept of "Virtual University" was developed for surgeons in the field of laparoscopic and minimally invasive surgery. This concept permits surgeons to update their knowledge from a distance any time they want. Using new technologies surgical techniques can be presented in a new fashion, more attractive for surgeons. With the aid of the internet we are now able to add animations and color illustrations with no limits, either in terms of size and number. Contributions were commissioned to international opinion leaders, under the control and seal of approval of national and international societies. The WebSurg site contains surgical techniques (rich illustrated), films presenting surgical procedures and films of expert's opinion. All partners (authors, reviewers, editors, sponsors, owners) must be in agreement with content, and also accept editorial independence. Scientific integrity and academic environment are the key factors to get high quality standards. Codes of ethics have been issued for internet information and must be followed by all websites.

Ovarian transposition by laparoscopy before radiotherapy in the treatment of Hodgkin's disease.

BACKGROUND: The use of inverted Y irradiation in the treatment of Hodgkin's disease with pelvic lymph node involvement can cause iatrogenic early menopause in young women as a result of ovarian exposure to radiation. Ovarian transposition protects the ovaries by removing them from the irradiation field. This surgical procedure, initially performed by laparotomy, can now be done by laparoscopy. METHODS: During the period July 1994 to April 1996, laparoscopic ovarian transposition was performed on 4 young women with Hodgkin's disease 1 week before inverted Y radiotherapy. The surgical procedure, complications, length of hospitalization, and hormonal, clinical, and biologic results were evaluated. RESULTS: The mean duration of hospitalization was 4 days, and there were no postoperative complications. Iatrogenic menopause did not occur in any of the patients during the mean follow-up period of 20.75 months (range, 6-35 months; median, 20 months). CONCLUSIONS: Laparoscopy offers many advantages over laparotomy for ovarian transposition. This procedure, which can be performed without opening the abdominal wall, is highly efficient, requires only a short period of hospitalization, and leads to few postoperative complications. Laparoscopy is an attractive alternative to laparotomy for ovarian transposition in young women with advanced Hodgkin's disease who require pelvic radiotherapy.