Four decades of stem cell transplantation for Fanconi anaemia in the Netherlands.

This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty-two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m(2) and cyclophosphamide 30 mg/kg ± anti-thymocyte globulin - no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow-up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation-wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non-irradiation and busulfan-free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder.

Application of sepsis calculator in newborns with suspected infection.

OBJECTIVE: To compare actual antibiotic use to the stratification based on the sepsis calculator in newborns with suspected early onset sepsis (EOS). To investigate differences in EOS risk and vital signs between newborns that received early (<12 h) versus late antibiotics (≥12 h of life). METHODS: Newborns born ≥34 weeks gestation in 2014 treated with antibiotics started within 72 h after birth were included. We calculated the risk per 1000 live births and retrospectively assigned each newborn to one of four recommended categories using the sepsis calculator. RESULTS: There were 2094 newborns, 111 (5.3%) received antibiotics and 108 newborns were included. The incidence of culture-proven EOS was 0.096%. In 57 newborns, the advice of the sepsis calculator was not to start antibiotic therapy. Antibiotic treatment was started early in 66 (61%) and late in 42 (39%) newborns. In the "late treatment" group, clinical condition deteriorated, including two newborns with culture-proven EOS. Tachypnea and respiratory distress were significantly more present. CONCLUSION: Antibiotic use could be reduced by more than 50%. Newborns with initial low sepsis risk score clinically deteriorated beyond 12 h of life. Continuous good clinical observation remains very important. Prospective validation is necessary to evaluate the safety of this approach.