Children diagnosed with acute myeloid leukaemia (paediatric AML [pAML]) have limited treatment options and relapse rates due to chemoresistance and refractory disease are over 30%. Current treatment is cytotoxic and in itself has long-lasting harsh side effects. New, less toxic treatments are needed. The bone marrow microenvironment provides chemoprotection to leukaemic cells through cell communication and interaction with mesenchymal stem cells (MSCs), but this is not well defined in pAML. Using primary patient material, we identify a cell contact-independent mechanism of MSC-mediated chemoprotection involving extrinsic soluble factors that is abrogated through inhibition of the JAK/STAT and ERK pathways.

A 57-year-old woman was referred for investigation of chronic thrombocytopenia prior to elective hip replacement. Her blood count showed haemoglobin concentration 129 g/L, MCV 96 fL, WBC 6.5 × 109/L, neutrophils 3.9 × 109/L, lymphocytes 1.8 × 109/L, monocytes 0.7 × 109/L, and platelets 58 × 109/L. She had a history of epilepsy treated with sodium valproate 1 g twice daily. Her blood film confirmed a true thrombocytopenia and was notable for abnormal neutrophil segmentation with frequent bilobed forms and condensed nuclear chromatin, resembling the Pelger-Huët anomaly, with normal cytoplasmic granulation (images, ×100 objective). A diagnosis of a myelodysplastic syndrome was considered but it was noted that sodium valproate therapy, particularly in large doses, can cause thrombocytopenia and pseudo-Pelger-Huët neutrophil features. The sodium valproate dose was titrated down and stopped after 4 weeks being replaced by levetiracetam. The platelet count improved to 156 × 109/L and 230 × 109/L at 4 and 9 weeks, respectively, and the neutrophil morphology returned to normal. Pseudo-Pelger neutrophil morphology can result from exposure to a number of medications including mycophenolate mofetil, tacrolimus, taxols, ganciclovir, and valproate. It is important to consider this possibility, particularly in patients with associated cytopenias. The authors declare no conflicts of interest.

Acute myeloid leukemia (AML) develops when there is a block in differentiation and uncontrolled proliferation of myeloid precursors, resulting in bone marrow failure. AML is a clinically, morphologically, and genetically heterogeneous disease, and biological differences between adult and childhood AML have been identified. AML comprises 15%-20% of all children < 15 years of age diagnosed with acute leukemia. Relapse occurs in up to 40% of children with AML and is the most common cause of death. Relapse arises from leukemic stem cells (LSCs) that persist after conventional chemotherapy. The treatment of AML is challenging, and new strategies to target LSCs are required. The cell surface marker CD33 has been identified as a therapeutic target, and novel anti-CD33 immunotherapies are promising new agents in the treatment of AML. This review summarizes recent developments emphasizing the genetic differences in adult and childhood AML and highlights the rationale for CD33 as a target for therapy in all age groups. Copyright (c) 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.

Keywords: multiple myeloma; renal impairment; myeloma therapy; renal replacement therapy; clinical