Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

Richardson PG, (2016) Blood, (Link to Abstract)


Veno-occlusive disease is a well-known complication of HSCT with a high mortality in patients developing multi organ failure of >80%. The authors assessed 102 patients with a diagnosis of veno-occlusive disease (VOD) and multi-organ failure. These patients were given defibrotide 25mg/kg/d and were compared to 32 historical controls. Survival at +100 days was 38.2% in the defibrotide group vs. 25% in controls (p=0.01). Day +100 complete response was seen in 25.5% in the treatment group vs. 12.5% in controls. Adverse events were encountered in a similar incidence in the two groups. Day +180 survival was not statistically significant but the authors point out that the causes of death were not directly related to VOD.

* Defibrotide 25mg/kg/d in patients with multi-organ failure was safe and survival was improved at +100 days but not at +180 days. In conclusion, defibrotide can be given in multi-organ failure due to VOD but long-term survival benefits were not shown.

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor StudyBreast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhoo

Henderson, TO, (2016) Journal of Clinical Oncology (Link to abstract)


Another study delves into the Childhood Cancer Survivors Study (CCSS) cohort and uses their big numbers to find a small signal. In particular, female survivors are at a higher risk of breast cancer at a young age than their siblings even when they receive no radiotherapy. Although the standardized incidence ratio (similar to relative risk) is high at 4.0 compared to the general population, the absolute risk by age 45 is 1.2% in survivors. The biggest risk factors for developing breast cancer were initial diagnosis of ALL or sarcoma and higher doses of alkylators or anthracyclines.

* This study should make us think about how we follow up our survivors. The findings seem to draw attention to high doses of anthracyclines and alkylators as risk factors and this is physiologically plausible. However, breast cancer at a young age is a criterion for Li Fraumeni syndrome and since sarcoma and hypodiploid ALL are also part of this disease it needs to be considered as a possible explanation. It’s also important to bear in mind that sarcoma patients get some of the highest doses of anthracyclines and alkylators introducing a confounder.

Neurodevelopmental Outcome at 2 Years of Age After General Anaesthesia and Awake-Regional Anaesthesia in Infancy (GAS): an International Multicentre, Randomized Controlled Trial

Davidson, AJ, 2016, The Lancet (Link to abstract)


This paper reports the secondary outcome of an RCT comparing neurodevelopmental outcomes in infants undergoing surgery for inguinal hernias. The randomization is between general anaesthesia (sevofluorane) and regional awake anaesthesia. The outcome reported here is neurodevelopmental outcome at 2 years of age by the Bayley scale. 360 infants less than 60 weeks postmenstrual age (premature babies were included) were in each arm in the intention to treat analysis although 69 in the regional group were converted to general anaesthesia. There was no difference in the mean of the composite cognitive score between the groups. The analysis reported here was a per-protocol analysis (not intention to treat).

* This is a hot area of contention in all fields of paediatrics – how much harm are we doing to our young patients when we put them under GA? This RCT (the first to ask this question) suggests the harm may not be real. But bear in mind that these children underwent a single short procedure – not multiple GAs over the course of the year the way our patients do. The primary outcome is the Weschler intelligence scale at 5 years of age and will be reported in the future.