Development of a rapid risk evaluation tool for herbs/drugs interactions in cancer patients: a multicentric experience in south of France.

Cancer patients use herbs in spite of severe interactions risks with major anticancer drugs. In daily practice, it is very difficult for oncologists to detect and define the risk of a herb-anticancer drug interaction (HDI). In this work, we realised a state of play in one of the most populated region of France by evaluating, through a specific questionnaire, the position of a representative panel of oncologists. About 80% of them thought that herbs interact with anticancer treatments whereas only 15.4% of them actually knew the real HDI. About 89.1% of them thought that a practical detection tool would be relevant and useful for their daily practice. Then, we constructed a tool in order to rapidly evaluate a HDI risk level. Based on experts' reviews and using a criticality matrix, we determined the HDI risk level between 11 herbs and 126 anticancer drugs. Then, we measured satisfactory of oncologists. All of them considered the tool as useful in their daily practice and then used it. This work highlighted that even if HDI has been integrated as a theoretical risk, its practical detection and risk evaluation is difficult to implement for oncologists in their daily practice. Thus, the tool we developed should answer to an unmet medical need.

Scn1a dysfunction alters behavior but not the effect of stress on seizure response.

Mutations in the voltage-gated sodium channel gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition, dysfunction in SCN1A is increasingly being linked to neuropsychiatric abnormalities, social deficits and cognitive disabilities. We have previously reported that mice heterozygous for the SCN1A R1648H mutation identified in a GEFS+ family have infrequent spontaneous seizures, increased susceptibility to chemically and hyperthermia-induced generalized seizures and sleep abnormalities. In this study, we characterized the behavior of heterozygous mice expressing the SCN1A R1648H mutation (Scn1a(RH/+)) and the effect of stress on spontaneous and induced seizures. We also examined the effect of the R1648H mutation on the hypothalamic-pituitary-adrenal (HPA) axis response. We confirmed our previous finding that Scn1a(RH/+) mutants are hyperactive, and also identified deficits in social behavior, spatial memory, cued fear conditioning, pre-pulse inhibition and risk assessment. Furthermore, while exposure to a stressor did increase seizure susceptibility, the effect seen in the Scn1a(RH/+) mutants was similar to that seen in wild-type littermates. In addition, Scn1a dysfunction does not appear to alter HPA axis function in adult animals. Our results suggest that the behavioral abnormalities associated with Scn1a dysfunction encompass a wider range of phenotypes than previously reported and factors such as stress exposure may alter disease severity in patients with SCN1A mutations.

Prior rituximab administration is associated with reduced rate of acute GVHD after in vivo T-cell depleted transplantation in lymphoma patients.

Rituximab is one of the most commonly used drugs in the treatment of B-cell non-Hodgkin lymphoma. Because of its ability to target CD20(+) lymphocytes, its use before allogeneic stem cell transplantation seemed to reduce risk of graft-vs.-host disease (GVHD) occurrence. We retrospectively analyzed the outcomes of adult patients diagnosed with CD20(+) lymphoproliferative disease undergoing allogeneic stem cell transplantation and receiving, or not receiving, rituximab up to 3 months before transplantation. Analysis on a cohort of 57 patients showed a protective role of rituximab on the occurrence of acute GVHD for those receiving anti-thymocyte globulin during conditioning (n = 39). Grade 2 to 4 and 3 to 4 acute GVHD occurred in 10% vs. 48% (p = 0.03) and 0% vs. 24% (p = 0.08) in the rituximab and no-rituximab groups, respectively. No impact on chronic GVHD was observed. These results confirm a protective role of rituximab on the occurrence of GVHD and enhance further investigation on future studies aimed at reducing GVHD incidence.