Background The BCL‐2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population in combination regimens. Although extensive data exist for adult myeloid malignancies, there are limited preclinical data on the efficacy and/or dosing of venetoclax for pediatric myelodysplastic syndrome (MDS) or AML and thus little information to guide use of this regimen in pediatric patients. Our objective was to describe our single‐center experience with venetoclax in combination with the hypomethylating agent 5‐azacitidine (aza) in pediatric patients with MDS or AML. Procedure We conducted a retrospective chart review of patients treated at Children's Hospital Colorado prior to March 2020 with at least one cycle of ven/aza. Patients were included if between the ages of 1 and 25 years with a diagnosis of high‐grade MDS or AML. AML patients had relapsed or primary refractory disease or were deemed poor candidates for standard chemotherapy. Results Eight patients received ven/aza, two for high‐grade MDS and six for AML. Ven/aza was well tolerated by all patients. The most common adverse events seen with this regimen were gastrointestinal and hematologic. Morphologic responses were seen in six patients including both patients with MDS. All four AML responders became minimal residual disease negative. Three responders have thus far proceeded to allogeneic hematopoietic stem cell transplant following ven/aza. Conclusions Our clinical experience suggests that ven/aza is a safe and promising regimen that should be further explored with late‐phase clinical trials.

Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.

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Excellent outcomes for patients with Wilms' tumour (WT), >90% for all stages together, have been achieved through researching WT in multicentre and multinational trials and studies in the last 50 years, led by two major groups-the International Society of Paediatric Oncology (SIOP) and the Children's Oncology Group (COG) (previously the National Wilms' Tumour Study Group). Despite the two groups having different approaches, the survival outcomes are remarkably similar. In general, in the SIOP approach, which is followed in Europe and most other countries around the world, patients are first treated with preoperative chemotherapy; this is followed by surgery and, if necessary, postoperative chemotherapy and radiotherapy. In the COG approach, which is mainly followed in North America, patients are treated with upfront surgery, followed, if necessary, by postoperative chemotherapy and radiotherapy. In both groups, postoperative treatment primarily depends on tumour histological classification and stage, although, in recent studies, other prognostic factors have also been included (tumour volume, response to preoperative chemotherapy, and molecular markers). Owing to separate initial treatments, there are differences in histological assessment and subtyping of WT, and, more importantly, in staging criteria. In this review, we discuss the similarities and differences between the two groups in order to help pathologists who are dealing with WT to understand and follow the pathological protocol that is appropriate for a particular case, because, in many centres, both approaches may be followed, depending on individual case/patient circumstances.

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