Myelodysplastic syndromes (MDS) are characterized by inefficient hematopoiesis and result in peripheral cytopenia. This heterogenous disease group arises from clonal disorders of hematopoietic stem cells. Several cohort studies and numerous case reports have highlighted a link between MDS and autoimmune disorders. Patients with MDS are more prone to develop particular systemic inflammatory diseases. On the other hand, patients suffering from autoimmune diseases are at higher risk to develop MDS. The scope of this article is to review the association between myelodysplasia and autoimmunity. It gives practical clues when to look for MDS in a patient suffering from autoimmunity and lists the main autoimmune diseases which may complicate the course of a MDS.

Breast cancers are highly radiosensitive since the risk of recurrences and of mortality after adjuvant radiotherapy following breast-conserving surgery is decreased by 15.7% and 3.8%, respectively at 10 years. The total dose if irradiation also significantly increases local control: a boost of 16 Gy to the tumour bed after breast-conserving surgery reduces the absolute risk of recurrence by 4% at 10 years. Breast cancers are sensitive to the dose per fraction, as shown by the results from four randomized trials which compared standard irradiation (50 Gy/25 fractions) with a hypofractionated scheme: no statistical difference was observed in locoregional recurrence and overall survival at 10 years. The α/β ratio, which reflects the dose per fraction and is theoretically over 10 Gy for tumour tissues, has been estimated between 2.2 and 4.4 Gy for breast cancers. Molecular abnormalities, such as overexpression of HER1 (especially in triple negative breast cancer) and HER2, induce a higher radioresistance. In vitro studies showed that targeted therapies, which block these receptors, increase breast cancer radiosensitivity. Tumour stem cells have been identified in breast cancers and are characterized by a higher radioresistance. This radioresistance could be related to a better repair of radiation-induced DNA damages and a decrease of reactive oxygen species (ROS), which are involved in their occurrence. In the future, a better understanding of genetics tumour abnormalities will allow to identify new radiosensitivity settings in breast cancers.

Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

Philadelphia or BCR-ABL positive acute lymphoblastic leukemia (PH+ ALL) is the most common and severe of adult ALL. The only potentially curator treatment remains allogeneic hematopoietic stem cells transplantation (SCT) in first complete remission. The use of imatinib has revolutionized the treatment of chronic myeloid leukemia. Its incorporation into PH + ALL protocols also improved the prognosis of this disease giving better complete remission rates compared to chemotherapy alone. The treatment of patients not eligible for SCT remains controversial. Prolonged use of high dose tyrosine kinase inhibitors (TKI) (ie: imatinib at 600 or 800 mg/j) as maintenance therapy seems to be a reasonable approach. We present a case of prolonged molecular remission of PH+ ALL under TKI alone as maintenance therapy.

In solid organ transplant, immunosuppressive therapy helped to increase graft and patient survival. However, these treatments are associated with toxic risks and infectious or tumor complications. The identification of immunoregulatory properties of regulatory cells and in particular Mesenchymal Stem Cells opens new therapeutic perspectives in the prevention of acute rejection and for the treatment of chronic rejection. In this review we will describe immunoregulatory properties of these cells and their potential use in solid organ transplantation.

Mesenchymal stromal cells are multipotent cells found in a large number of adult tissues. Their ability to participate in the repair of these damaged tissues is the origin of the enthusiasm that they elicit in the field of cell therapy. It gradually became apparent that their ability to change a pathological environment is more related to their ability to modulate the behavior of other cell types than their capacity of diferentiation. Recent years have expanded the scope of our knowledge about their way of communication with their environment but also the amount of information that they receive from this environment. In this brief review, we will present some of the mechanisms by which MSCs can communicate remotely with other cell types and how it currently appears possible to direct the secretion pattern of these cells.

Sonic Hedgehog (Shh) pathway is physiologically activated during embryogenesis and development. It plays a role in idiopathic lung fibrosis and is also activated in several solid cancers.

In order to overcome the quasi-total inability of the mammalian central nervous system to regenerate in response to injuries, and in parallel to the studies dedicated to prevent neuronal loss under these circumstances, alternative approaches based on the programming of pluripotent cells or the reprogramming of somatic cells into neurons have recently emerged. These uniquely combine growing knowledge of the mechanisms that underlie neurogenesis and neuronal specification during development to the most recent findings of the molecular and epigenetic mechanisms that govern the acquisition and maintenance of cellular identity. Here, we discuss the possibility to instruct the regeneration of the central nervous system from within for therapeutic purposes, in light of the recent works reporting on the generation of neurons by direct conversion of various cerebral cell types in vitro and in vivo.

The concept of cancer stem cell (CSC) was established from models of leukemogenesis explaining tumor repopulation by the clonogenic properties of this specific population of tumoral cells. Among solid tumors, glioblastoma are currently the most documented models. Cancer stem cells reside in specific locations within tumors called niches. Anatomically, two complementary niches have been described in glioblastoma. The first one is a perivascular niche composed of vessels (endothelial cells, pericytes) and their microenvironment (integrins, interleukins) constitutive the nest of "normal" neural stem cells and cancer stem cells. The second one is a hypoxic niche found in regions with low oxygen tension such as the core of the tumor. In these niches, mutual interactions between CSC and their microenvironment involving the activation of multiple signaling pathways promote stemness maintenance and tumor propagation. The median overall survival of glioblastoma does not exceed 15 months despite an aggressive multimodal treatment, thus the therapeutic targeting of these niches, by systemic agents or radiotherapy, in order to inhibit the signaling pathways involved in the maintenance of the CSC niches, represents a major challenge. The combination of these two strategies appears promising and many clinical trials are underway.

Oral mucositis is a very common complication of allograft. However, preventive treatments are still limited. The objective of this study is to identify risk factors for onset of oral mucositis in patients undergoing allogeneic hematopoietic stem cells transplantation (HSCT), to measure clinical consequences and to study their evolution according to type of prevention.

Extranodal NK/T-cell lymphoma (ENKTL) is a rare form of non-Hodgkin's lymphoma and carries a poor prognosis. Depending on the primary sites of anatomical involvement, it is subcategorized into nasal or extra-nasal ENKTL. Cutaneous involvement is the second localization reported for these lymphomas.