Pharmacologic Therapies to Prevent Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML

Novel strategies to prevent and overcome relapse after allogeneic hematopoietic cell transplantation in acute lymphoblastic leukemia

The outcome of B-cell acute lymphoblastic leukemia (B-ALL) has improved over time with the incorporation of multi-agent chemotherapy in the treatment landscape as well as the recent approval of immunotherapeutic agents allowing a larger proportion of patients to undergo allogeneic hematopoietic cell transplantation (allo-HCT) which is still considered a potential curative approach. However, relapse post-transplant is still occurring and constitutes a common cause of treatment failure in B-ALL. The present review aims to discuss the novel strategies and therapies used to prevent and overcome relapse post allo-HCT in patients with ALL, focusing on the role of tyrosine kinase inhibitors in Philadelphia chromosome positive B-ALL, the role of innovative agents such as blinatumomab and inotuzumab ozogamicin, and finally the role of cellular therapy

Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3 internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia . Because of the poor prognosis associated with FMS-like tyrosine kinase 3 internal tandem duplication mutated Acute myeloid leukemia, allogeneic-hematopoietic stem-cell transplantation was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays. Similarly, recent progress in allogeneic-hematopoietic stem-cell transplantation includes improvement of transplant techniques, the use of haplo-identical donors in patients lacking an HLA matched donor, and the introduction of FLT3 inhibitors as posttransplant maintenance therapy. Nevertheless, current transplant strategies vary between centers and differ in terms of transplant indications based on the internal tandem duplication allelic ratio and concomitant nucleophosmin-1 mutation, as well as in terms of post-transplant maintenance/consolidation. This review generated by international leukemia or transplant experts, mostly from the European Society for Blood and Marrow Transplantation, attempts to develop a position statement on best approaches for allogeneic-hematopoietic stem-cell transplantation for acute myeloid leukemia with FMS-like tyrosine kinase internal tandem duplication including indications and modalities of allogeneic-hematopoietic stem-cell transplantation and on potential optimization of post-transplant maintenance with FMS-like tyrosine kinase inhibitors

Elements on the emergence of the diversity of forms of the management control function : the case of companies in the Lebanese insurance market

Notre recherche est focalisée sur le rôle du contrôleur de gestion dans les compagnies d’assurance d’un pays appartenant à une région de perturbations économiques et politiques continues tel que le Liban.Ainsi, notre thèse vise à saisir les conditions dans lesquelles les sociétés d’assurance libanaises choisissent leurs pratiques de contrôle de gestion, et plus précisément à déterminer les différents facteurs de contingence qui peuvent influer sur la fonction contrôle de gestion des compagnies d’assurance au Liban. L’emploi de deux méthodologies a permis d’obtenir un éclairage approfondi des pratiques de contrôle de gestion dans les sociétés d’assurance au Liban. L’étude exploratoire menée auprès de sept compagnies d’assurance a mis en exergue l’existence de deux types de fonction contrôle de gestion, qui se distinguent par leur autonomie relative vis-à-vis de la direction générale de l’entreprise.Plus particulièrement, le rôle du contrôleur de gestion dépend de sa position dans la structure, et sa marge d’autorité varie selon son rattachement hiérarchique.Une typologie plus large est réalisée ensuite par une étude quantitative approfondie à l’aide d’un questionnaire, menée auprès de seize compagnies d’assurance libanaises. L’étude quantitative a apporté un éclairage plus précis en mettant en exergue l’existence de trois types du système de contrôle de gestion dans les sociétés d’assurance libanaises : le système de contrôle de gestion organisationnel, le système de contrôle de gestion partagé, et le système d’information général. L’adoption d’un de ces trois types diffère selon des facteurs de contingence comme la taille, l’internationalisation de la société, la nature de l’actionnariat…, mais aussi la conception de la fonction de contrôle de gestion par la gouvernance de l’organisationOur research focuses on the role of the management controller in insurance companies in a country belonging to a region of continuous economic and political disturbances such as Lebanon.Thus, our thesis aims to capture the conditions under which Lebanese insurance companies choose their management control practice, and more specifically to determine the different contingency factors that can influence the management control function of insurance companies in Lebanon.The use of two methodologies has provided an insight into management control practices in insurance companies in Lebanon.The exploratory study conducted within seven insurance companies highlighted the existence of two types of management control functions, which are distinguished by their relative autonomy vis-à-vis of the company general management.More particularly, the role of the management controller depends on his position within the structure, and his authority margin varies according to his hierarchical connection.A broader typology is then carried out by a thorough quantitative study using a survey conducted among sixteen Lebanese insurance companies.The quantitative study shed more light on the existence of three types of management control systems in Lebanese insurance companies: the organizational management control system, the shared management control system, and the general information system. The adoption of one of these three types differs according to several contingency factors such as the company’s size, the internationalization of the company, the nature of the shareholding ..., and also according to the conception of the management control function designated by the governance of the organizatio

Éléments sur l’émergence de la diversité des formes de la fonction contrôle de gestion: le cas des entreprises du marché libanais de l’assurance

Texte intégral accessible uniquement aux membres de l'Université de Lorraine.Our research focuses on the role of the management controller in insurance companies in a country belonging to a region of continuous economic and political disturbances such as Lebanon.Thus, our thesis aims to capture the conditions under which Lebanese insurance companies choose their management control practice, and more specifically to determine the different contingency factors that can influence the management control function of insurance companies in Lebanon.The use of two methodologies has provided an insight into management control practices in insurance companies in Lebanon.The exploratory study conducted within seven insurance companies highlighted the existence of two types of management control functions, which are distinguished by their relative autonomy vis-à-vis of the company general management.More particularly, the role of the management controller depends on his position within the structure, and his authority margin varies according to his hierarchical connection.A broader typology is then carried out by a thorough quantitative study using a survey conducted among sixteen Lebanese insurance companies.The quantitative study shed more light on the existence of three types of management control systems in Lebanese insurance companies: the organizational management control system, the shared management control system, and the general information system. The adoption of one of these three types differs according to several contingency factors such as the company’s size, the internationalization of the company, the nature of the shareholding ..., and also according to the conception of the management control function designated by the governance of the organizationNotre recherche est focalisée sur le rôle du contrôleur de gestion dans les compagnies d’assurance d’un pays appartenant à une région de perturbations économiques et politiques continues tel que le Liban.Ainsi, notre thèse vise à saisir les conditions dans lesquelles les sociétés d’assurance libanaises choisissent leurs pratiques de contrôle de gestion, et plus précisément à déterminer les différents facteurs de contingence qui peuvent influer sur la fonction contrôle de gestion des compagnies d’assurance au Liban. L’emploi de deux méthodologies a permis d’obtenir un éclairage approfondi des pratiques de contrôle de gestion dans les sociétés d’assurance au Liban. L’étude exploratoire menée auprès de sept compagnies d’assurance a mis en exergue l’existence de deux types de fonction contrôle de gestion, qui se distinguent par leur autonomie relative vis-à-vis de la direction générale de l’entreprise.Plus particulièrement, le rôle du contrôleur de gestion dépend de sa position dans la structure, et sa marge d’autorité varie selon son rattachement hiérarchique.Une typologie plus large est réalisée ensuite par une étude quantitative approfondie à l’aide d’un questionnaire, menée auprès de seize compagnies d’assurance libanaises. L’étude quantitative a apporté un éclairage plus précis en mettant en exergue l’existence de trois types du système de contrôle de gestion dans les sociétés d’assurance libanaises : le système de contrôle de gestion organisationnel, le système de contrôle de gestion partagé, et le système d’information général. L’adoption d’un de ces trois types diffère selon des facteurs de contingence comme la taille, l’internationalisation de la société, la nature de l’actionnariat…, mais aussi la conception de la fonction de contrôle de gestion par la gouvernance de l’organisatio

Polymeres insolubles fonctionnels : affinite specifique pour les anticorps anti VIII:C

CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Pharmacologic Strategies for Post-Transplant Maintenance in Acute Myeloid Leukemia: It Is Time to Consider!

Patients with high-risk acute myeloid leukemia are offered allogeneic hematopoietic cell transplantation (allo-HCT) in first remission to reduce risk of relapse. However, disease recurrence remains the major reason of allo-HCT failure, occurring in around 35–45% of patients, and leading to dismal outcomes. Strategies to reduce the risk of relapse are greatly needed, especially in the early post-transplant phase where the graft-versus-leukemia (GVL) effect is not yet activated. Some practices include the use of myeloablative conditioning regimens, close monitoring of measurable residual disease and donor chimerism, rapid tapering of immunosuppression, and implementation of pre-emptive strategies as the use of donor lymphocyte infusion. However, it’s time to consider prophylactic pharmacologic interventions post allo-HCT that aim at maintaining leukemic clones under control by both direct cytotoxic activity and by enhancing the GVL effect. In this current review, available data on drugs targeting epigenetic pathways like azacitidine, or actionable mutations like FLT3 and IDH1/2 inhibitors used as maintenance post allo-HCT, will be discussed

Primary small cell carcinoma of the breast: a case report

Abstract Background Neuroendocrine breast cancer is a rare entity that was defined in 2003 by the World Health Organization as a separate breast cancer subtype. The diagnosis of neuroendocrine breast cancer requires the presence of neuroendocrine features in at least 50% of malignant cells, the exclusion of non-mammary primary tumors, as well as the presence of an in situ component in breast histology. The treatment and prognosis of neuroendocrine breast cancer are still not well established. Small cell carcinoma of the breast is a subtype of neuroendocrine cancer, resembling small cell carcinoma of the lung. It has a very poor prognosis and warrants treatment with platinum-based chemotherapy. Case presentation We herein report the case of a 47-year-old white woman with a left breast mass that was found to be an early-stage, high-grade small cell carcinoma of the breast. Positron emission tomography-computed tomography imaging excluded any other primary disease. Our patient underwent a left total mastectomy with sentinel lymph node biopsy and received cisplatin-based adjuvant chemotherapy. Our patient remains free of disease to date. Conclusions This case report sheds light on a rarely described disease and provides a comprehensive approach to diagnosis and management. Neuroendocrine carcinoma of the breast is a well-defined histologic subtype of breast cancer. Small cell carcinoma of the breast is a rare subtype of neuroendocrine breast cancer. Due to the rarity of this entity, prognosis has still not been well established, and treatment has not been standardized, cisplatin-based treatment has been used in this case similar to small cell carcinoma of the lung