Infant acute myeloid leukemia (AML) is a rare subgroup of AML of children <2 years of age. It is as frequent as infant acute lymphoblastic leukemia (ALL) but not clearly distinguished by study groups. However, infant AML demonstrates peculiar clinical and biological characteristics, and its prognosis differs from AML in older children. Acute megakaryoblastic leukemia (AMKL) is very frequent in this age group and has raised growing interest. Thus, AMKL is a dominant topic in this review. Recent genomic sequencing has contributed to our understanding of infant AML. These data demonstrated striking features of infant AML: fusion genes are able to induce AML transformation without additional cooperation, and unlike AML in older age groups there is a paucity of associated mutations. Mice modeling of these fusions showed the essential role of ontogeny in the infant leukemia phenotype compared to older children and adults. Understanding leukemogenesis may help in developing new targeted treatments to improve outcomes that are often very poor in this age group. A specific diagnostic and therapeutic approach for this age group should be investigated.

Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.

Background: Preventing premature ovarian failure (POF) is a major challenge in oncology. With conventional regimens, cytotoxicity-associated POF involves primordial follicles (PF) pool depletion by apoptosis or overactivation mechanisms, notably mediated by the ABL/TAp63 and PI3K/Akt/mTOR pathways. New anticancer treatments have been designed to target pathways implicated in tumor growth. Although concerns regarding fertility arise with these targeted therapies, we hypothesized that targeted therapies may exert off-tumor effects on PF that might delay POF. We provide an overview of evidence concerning these off-tumor effects on PF. Limitations and future potential implications of these findings are discussed. Design: PubMed was searched by combining Boolean operators with the following keywords: fertility, ovarian, follicle, anti-tumoral, cancer, targeted, cytotoxic, and chemotherapy. Results: Cisplatin-related PF apoptosis via the ABL/TAp63 pathway was targeted with a tyrosine kinase inhibitor, imatinib, in mice, but effects were recently challenged by findings on human ovarian xenografts in mice. In cyclophosphamide-treated mice, PI3K/Akt/mTOR pathway inhibition with mTOR inhibitors and AS101 preserved the PF pool. Proteasome and GSK3 inhibitors were evaluated for direct and indirect follicle DNA damage prevention. Surprisingly, evidence for cytotoxic drug association with PF pool preservation was found. We also describe selected non-anticancer molecules that may minimize gonadotoxicity. Conclusion: Not all anticancer treatments are associated with POF, particularly since the advent of targeted therapies. The feasibility of associating a protective drug targeting PF exhaustion mechanisms with cytotoxic treatments should be evaluated, as a way of decreasing the need for conventional fertility preservation techniques. Further evaluations are required for transfer into clinical practice. Implications for Practice: Anticancer therapies are associated with infertility in 10%–70% of patients, which is the result of primordial follicles pool depletion. Alone or associated with gonadotoxic treatments, some targeted therapies may exert favorable off-targets effects on the primordial follicle pool by slowing down their exhaustion. Current evidence of these effects relies on murine models or human in vitro models. Evaluation of these protective strategies in humans is challenging; however, if these results are confirmed with clinical and biological data, it not only could be a new approach to female fertility preservation but also would change standard fertility strategies.

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV₁) threshold, focus on obstructive defects defined by FEV₁/vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT.