No abstract

Androgens have represented the historical therapeutic backbone of bone marrow failure (BMF) syndromes. However, their role has been rarely analyzed in prospective setting and systematic and long-term data are currently unavailable regarding their usage, effectiveness and toxicity in both acquired and inherited BMF. Here, taking advantage of a unique disease-specific international dataset, we retrospectively analyzed the so far largest cohort of BMF patients who received androgens before or in absence of an allogeneic hematopoietic cell transplantation (HCT), reappraising their current use in these disorders. We identified 274 patients across 82 EBMT affiliated centers, 193 with acquired (median age of 32) and 81 with inherited BMF (median age of 8 years). With a median duration of androgen treatment of 5.6 and 20 months respectively, complete/partial remission rates at 3 months were of 6%/29% in acquired and 8%/29% in inherited disorders. Five-year overall survival and failure free survival (FFS) were respectively 63% and 23% in acquired and 78% and 14% in inherited contexts. Androgen initiation after second line treatments for acquired, and after > 12 months post-diagnosis for inherited group were identified as factors associated with improved FFS in multivariable analysis. Androgen use was associated with a manageable incidence of organ-specific toxicity and low rates of solid and hematological malignancies. Sub-analysis of transplant-related outcomes after exposure to these compounds showed probabilities of survival and complications similar to other transplanted BMF cohorts. This study delivers a unique opportunity to track androgen use in BMF syndromes and represents the basis for general recommendations on their use on behalf of the SAAWP of the EBMT.

A 4-month-old female infant referred to our care for three episodes of melena, vomiting with blood streaks and hyporeactivity. She was being treated for infant B-cell precursor acute lymphoblastic leukaemia according to AIEOP/BFM LLA 2017. Her family history was negative for gastrointestinal diseases or bleeding disorder. Upon clinical examination, we observed cold extremities, skin pallor, tachycardia, and blood tests showed: haemoglobin 7.8 g/dL, haematocrit 29.2%, albumin 2.8 g/dL, prothrombin time (PT) 48.2%, activated partial thromboplastin time (aPTT) 36.8 s, fibrinogen 58 mg/dL. Abdominal X-ray was negative. Initially, intravenous proton-pump inhibitors, transfusion of packed red blood cells and fibrinogen were administered. Subsequently, we performed emergency upper endoscopy under general anaesthesia. During the procedure, we noted the presence of a dilated visible vessel with oozing haemorrhage at the level of the superior duodenal flexure (Fig. 1a,b), but did not observe any muco-sal abnormality in other examined sections or surrounding the lesion.What is the most likely diagnosis? (Answer on page 155