Chromosome fragility in Fanconi anemia patients: diagnostic implications and clinical impact

International audienceFanconi anemia (FA) is a rare syndrome characterized by bone marrow failure, malformations, and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing agents such as DEB or MMC is the gold standard test for the diagnosis of FA. In this study we present data from 198 DEB-induced chromosome fragility tests in non-FA and in FA patients where information on genetic subtype, cell sensitivity to MMC and clinical data were available. This large series allowed us to quantify the variability and the level of overlap in ICL-sensitivity among FA patients and normal population. In this article we propose a new chromosome fragility index that provides a cut-off diagnostic level to unambiguously distinguish FA patients, including mosaics, from non-FA individuals. Spontaneous chromosome fragility and its correlation with DEB-induced fragility was also analyzed, indicating that, while both variables are correlated, 54% of FA patients do not have spontaneous fragility. Our data reveal a correlation between malformations and sensitivity to ICLs, This correlation is also statistically significant when the analysis is restricted to the patients from the FA-A complementation group and suggests that genome instability during embryo development may be related to malformations in FA. Finally, chromosome fragility does not correlate with the age of onset of hematological disease, indicating that DEB-induced chromosome breaks in T-cells has no prognostic value in FA

Effect of poloxamer 188 vs placebo on painful vaso-occlusive episodes in children and adults with sickle cell disease : a randomized clinical trial

Key PointsQuestionCan poloxamer 188, an agent that is reported to reduce blood viscosity and cell-cell interactions, effectively reduce the duration of vaso-occlusive episodes (painful crises) in hospitalized patients with sickle cell disease? FindingsIn this randomized clinical trial that included 388 children and adults with sickle cell disease, treatment with poloxamer 188 vs placebo resulted in mean time to last dose of parenteral opioids during vaso-occlusive episodes of 81.8 vs 77.8 hours, a difference that was not statistically significant. MeaningAmong patients with sickle cell disease, poloxamer 188 did not significantly shorten the duration of painful vaso-occlusive episodes

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Key PointsQuestionCan poloxamer 188, an agent that is reported to reduce blood viscosity and cell-cell interactions, effectively reduce the duration of vaso-occlusive episodes (painful crises) in hospitalized patients with sickle cell disease? FindingsIn this randomized clinical trial that included 388 children and adults with sickle cell disease, treatment with poloxamer 188 vs placebo resulted in mean time to last dose of parenteral opioids during vaso-occlusive episodes of 81.8 vs 77.8 hours, a difference that was not statistically significant. MeaningAmong patients with sickle cell disease, poloxamer 188 did not significantly shorten the duration of painful vaso-occlusive episodes