Environmental Factors in Northern Italy and Sickle Cell Disease Acute Complications: A Multicentric Study.

BACKGROUND: Environmental factors seem to influence clinical manifestations of sickle cell disease (SCD), but few studies have shown consistent findings. We conducted a retrospective multicentric observational study to investigate the influence of environmental parameters on hospitalization for vaso-occlusive crises (VOC) or acute chest syndrome (ACS) in children with SCD. METHODS: Hospital admissions were correlated with daily meteorological and air-quality data obtained from Environmental Regional Agencies in the period 2011-2015. The effect of different parameters was assessed on the day preceding the crisis up to ten days before. Statistical analysis was performed using a quasi-likelihood Poisson regression in a generalized linear model. RESULTS: The risk of hospitalization was increased for low maximum temperature, low minimum relative humidity, and low atmospheric pressure and weakly for mean wind speed. The diurnal temperature range and temperature difference between two consecutive days were determined to be important causes of hospitalization. For air quality parameters, we found a correlation only for high levels of ozone and for low values at the tail corresponding to the lowest concentration of this pollutant. CONCLUSIONS: Temperature, atmospheric pressure, humidity and ozone levels influence acute complications of SCD. Patients' education and the knowledge of the modes of actions of these factors could reduce hospitalizations.

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.