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Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare bone marrow failure syndrome associated with thrombocytopenia and a tendency to progress to aplastic anemia. Mutations in the c-MPL gene encoding for thrombopoietin receptor have been identified in the majority of the patients. Previous studies suggest a genotype-phenotype correlation wherein the severity of the disease depends on the type of mutation present and residual thrombopoietin receptor activity. The present study describes the clinical and genetic findings on a series of 7 patients with CAMT, 3 of them siblings. The patients were homozygous for 5 mutations in the c-MPL gene, including 3 unique ones: c.212+5G>A, C76T, and G1162C. The clinical picture was variable; 1 patient who was homozygous for a nonsense mutation in exon 1 (C76T) developed infantile acute lymphoblastic leukemia, whereas patients who were homozygous for a splice-site mutation (c.212+5G>A) expressing both normal and mutated transcripts had a milder clinical course. As previously suggested, c-MPL mutation analysis in CAMT patients helps to predict the clinical course and to provide optimal therapy.

We found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2Á2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3Á75; 95% CI 1Á51-9Á37; P = 0Á004) and with increasing age (OR 3Á58; 95% CI 1Á24-9Á77; P = 0Á01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9Á43; 95% CI 1Á47-60Á66; P = 0Á02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6Á42; 95% CI, 1Á01-40Á94; P = 0Á05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 AE 8% and five-year overall survival was 70 AE 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable. ALL, acute lymphoblastic leukaemia; AML, acute myeloid leukaemia; SCT, stem cell transplantation. *Variables are presented as n (%), unless otherwise stated. † The dash indicates that the variable was entered into the initial multivariate logistic regression model based on its P value in the univariate analysis (≤0Á10), but it was removed from the final model through the backward elimination procedure. ‡ Lymphocytopenia and monocytopenia were not included in the multivariate analysis as only a subcategory of patients had evaluable data. Surgical interventions were not included in order to avoid possible selection bias. SCT was not included due to its high correlation with relapsed and refractory disease (phi coefficient = 0Á78 and 0Á65, respectively).

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