High rate of hematological responses to sorafenib in FLT3‐ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation

Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3‐ITD‐positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off‐label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post‐transplantation FLT3‐ITD‐positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand‐foot syndrome. None of the patients developed graft‐vs.‐host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T‐cell infusions. Six patients are alive and in remission at the last follow‐up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3‐ITD‐positive post‐transplantation relapses, manageable also in combination with other therapeutic strategies.     

Influence of intra- and extrauterine factors on infant sleep in the first 6 months of life

ObjectiveInfant sleep problems can affect the child's health. Maternal characteristics have been associated with the quality of infant sleep, but few studies have investigated the impact of intrauterine conditions. The aim of the study was to evaluate the association between adverse intrauterine environments (maternal smoking, hypertension, diabetes, and intrauterine growth restriction) and extrauterine factors on infant sleep in the first 6 months of life.MethodsProspective cohort study, including singleton and at-term infants. Mothers were interviewed after delivery and at 30 days, 3 months, and 6 months of life. Socioeconomic, breastfeeding, and sleep data were self-reported by mothers using semi-structured interviews. Maternal stress (Perceived Stress Scale) and postpartum depression symptoms (Edinburgh Postpartum Depression Scale) were assessed.ResultsThere was no statistically significant association between intrauterine environments and the sleep of infants of the 359 mother–child dyads investigated. Total infant sleep time decreased from approximately 13–11 h from 30 days to 6 months of age (p < 0.001) and the longest period of uninterrupted sleep increased from approximately 4–6 h during the same period (p < 0.001). Breastfed infants slept longer in 24-h periods in the first month, but they woke up more often throughout the night when compared to infants receiving formula. Mothers with depressive symptoms reported increased sleep latency time.ConclusionsAdverse intrauterine environments did not significantly affect sleep measures in the first 6 months of life. Maternal characteristics and practices, however, were associated with infant sleep, suggesting that environmental factors significantly contribute to sleep quality early in life.