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The main objectives of multidisciplinary clinical investigation center (CIC-P) are to facilitate the availability of new drugs for patients, to enhance the visibility and attractiveness of French clinical research, to improve the quality of early phase trials, and to enhance the value of academic research by evaluating molecules in rare diseases. Since 2017, the CIC-P has been committed to a quality approach process, launching in 2018 its first satisfaction survey on patient care and clinical trial management of all its employees. A second satisfaction survey targeted by profession type was to be launched in 2020, in view of the requirements of the ISO 9001:2015 standard, but the process was interrupted following the coronavirus diseases 2019 (COVID-19) pandemic. The successful reorganization of the CIC-P activity during the first containment of the COVID-19 pandemic was driven by the implementation of a quality management system that promotes continuous improvement through the organization and involvement of all the staff. This voluntary and participative approach motivated the CIC-P to apply for the organizational sesame. The ISO 9001:2015 certification of CIC-P aims at increasing its performance, to satisfying its customers and to fully integrate its activities in a continuous improvement process, according to the requirements of this international standard, through the deployment of quality tools such as The Deming wheel (PDCA), an indispensable tool for transformation and reorganization; the analysis of the environment by the strengths, weakness, opportunities, threats (SWOT) analysis tool; the analysis and management of risks by the FMEA method, and all with performance indicators (SMART) and precise objectives at each stage of a project/process. The implementation of satisfaction questionnaires remains the essential tool for evaluating the expectations and needs of interested parties, but also for improving the quality of CIC-P activities and services. All these tools put in place have allowed us to continuously improve the means of production and to constantly improve our organization., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The Clinical Investigations Center of Saint-Louis Hospital (CIC-1427) is a structure dedicated to clinical trials and mainly early phase trials (first-in-man administration, phase 1 and 2). These trials are conducted in a French Regional Health Agency (ARS) authorized structure. In March 2020, faced to the global COVID-19 pandemic and the French national lockdown measures, the CIC-1427 had to rapidly adapt its operating procedures to ensure the safety of both patients and staff., Study Objective: Ensuring optimal management of patients included in early phase clinical trials, while respecting the good clinical and professional practices (GCP/GPP) of the CICs protocol sponsors' requirements, patients' safety and clinical research multidisciplinary staff safety (nurses, caregivers' assistants (AS), clinical research assistants (CRA), clinical trial coordinators (CTC), project leaders, health executive and investigating physicians), in the context of the health crisis related to COVID-19., Methods and Results: Due to their activity, requiring on-site presence, each staff member of the CIC-1427 clinical research team had to adapt their daily activity to the constraints of the health crisis. New specific procedures were quickly developed to deal with the pandemic. Most of the on-site medical visits were replaced by virtual consults with biological assessments in the local laboratories. "Remote monitoring" replaced on-site monitoring visits. Treatments were sent to each patient's home via couriers after agreement of the CPPs of each protocol (Committee for the Protection of Persons). The essential visits were maintained on site thanks to the unfailing involvement of our clinical care team, with implementation of a specific sanitary protocol., Conclusion: The involvement of our entire multidisciplinary research team ensured that each patient was able to benefit from a personalized follow-up and to continue the treatment on-trial. The newly introduced procedures also allowed collection of a maximum of safety and efficacy data for clinical trial sponsors while complying with good regulatory practices. This set of procedures developed during the first epidemic wave, fundamentally helped setting the frame for a better coping during the subsequent pandemic waves., (Copyright © 2021 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

THE ROLE OF RUXOLITINIB IN THE TREATMENT OF MYELOPROLIFERATIVE NEOPLASMS: The discovery of the JAK2V617F mutation in 2005, present in 95% of polycythemia vera (PV) and in 55% of myelofibrosis (MF) patients, opened the way for a new era of targeted therapies for myeloproliferative neoplasms. Ruxolitinib was the first-in-class Janus Kinase (JAK) inhibitor approved for the management of these diseases. In PV patients, conventional treatment strategies including aspirin, phlebotomy, cytoreductive agents such as hydroxyurea and interferon, clearly provide clinical benefits. However, some patients develop resistance or intolerance to these treatments. Ruxolitinib has been approved for PV patients who are resistant to or intolerant of hydroxyurea, based on the results of the phase 3 RESPONSE study. This study showed that ruxolitinib improves hematocrit control, reduces splenomegaly, and ameliorate disease-related symptoms as compared with best available therapy. In MF patients, the only curative treatment is allogeneic stem cell transplantation, but it remains restricted to a limited group of patients with poor prognosis and who are eligible for such procedure associated with non-negligible transplant-related mortality. Other treatments are palliative and unlikely to prolong survival. Ruxolitinib has been approved in the United States for MF patients with intermediate or high-risk disease, and in Europe for disease-related splenomegaly or symptoms in adults with MF, based on phase 3 COMFORT-I and COMFORT-II studies. These studies showed that ruxolitinib was able to reduce splenomegaly, ameliorate symptoms, and improve survival. However, the journey is not finished yet since there are still important unmet needs for MF patients, including improvement in cytopenias, and significant modification of disease natural history., (© 2016 Société Française du Cancer. Publié par Elsevier Masson SAS.)

Introduction: Fever during a myelodysplastic syndrome can be due to infectious complications, systemic disease or acute transformation with clonal evolution., Case Report: A 51-year-old woman, with a 5q- syndrome and neutropenia, presented with a several week fever duration. Infectious work-up was negative and therapy with antibiotics had no influence on the clinical course. Neither bone marrow nor blood blasts were detected, but liver biopsy demonstrated significant blast infiltration compatible with the diagnosis of acute myeloid leukaemia (AML)., Conclusion: The absence of blasts in blood or bone marrow does not exclude the malignant transformation of a myelodysplastic syndrome to AML. Tissue biopsy may be necessary to confirm the leukaemic progression.

Primary thrombocythemia is a frequent myeloproliferative disorder that may be asymptomatic for a long period of time. Once the usual reactive causes have been excluded, further diagnosis requires specialized exploration. The severity level of the disease is not necessarily related to reduce survival rates, but to thrombotic or hemorrhagic complications that can affect quality of life. Myelofibrotic and acute leukemic transformations can also be long-term complications, possibly influenced by treatment strategy. Cytoreductive treatment is required in patients older than 60, or with a history of thrombosis or hemorrhage, or with a platelet count above 1 500 - 109/L. In cases where these indicators do not exist, there are no guidelines for treatment in France, and all investigators try to discriminate patients with a low vascular risk in order to avoid cytoreductive treatment. In fact, in the absence of curative treatment, it seems reasonable to avoid potentially leukemogenic drugs in younger patients.

In a 70 year old man with primary glomerulonephritis, severe anemia occurred after 4 years on hemodialysis and rHu-EPO. The usual mechanisms of EPO-resistance were excluded. A bone marrow sample showed red all aplasia. No circulating EPO could be detected; the serum inhibited the growth of erythroid precursors in bone marrow cultures. Immunoprecipitation identified an IgG anti-EPO, still active against deglycosylated EPO, i.e. directed against the peptidic matrix. Its high neutralising capacity and the absence of any immune abnormality rule out an auto-antibody. Anti-rHu EPO immunisation is a very rare occurrence, made severe by transfusion-dependence and the risk of hemosiderosis. An immuno-modulating treatment can therefore be justified.

Megakaryocyte proliferation in bone marrow is a feature common to the three Philadelphia negative chromosome myeloproliferative disorders (MPD)--essential thrombocythemia (ET), polycythemia vera, and myelofibrosis with splenic myeloid metaplasia--and chronic myelocytic leukemia. Enlarged megakaryocytes, clustering in close neighbouring with multilobulated nuclei are the hallmark of all the Philadelphia negative chromosome MPD. Clonality of hematopoietic cells, based on X-chromosome inactivation can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. A significant increase in circulating CFU-MK has been repeatedly observed in MPD as well as a spontaneous megakaryocyte colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation with a functional defect of the TPO-MPL pathway may play a major role in spontaneous megakaryocyte growth. There is presently no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However the role of platelets activation in the pathogenesis of ischemic erythromelalgia has been established.