Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of the biology of the disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management is needed to improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) and who experience relapse. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric ALL provide recommendations on the workup, diagnostic evaluation, and treatment of the disease, including guidance on supportive care, hematopoietic stem cell transplantation, and pharmacogenomics. This portion of the NCCN Guidelines focuses on the frontline and relapsed/refractory management of pediatric ALL.

Background/Aims: Adrenocortical carcinoma (ACC) is an aggressive childhood cancer. Limited evidence exists on a definite histopathological criterion to differentiate ACC from adrenocortical adenoma. The aim of this study was to investigate the clinicopathological data of children with ACC, identify prognostic factors, and validate a histopathological criterion to differentiate ACC from adrenocortical adenoma. Methods: This retrospective cohort included 41 children, followed at the Mayo Clinic from 1950 to 2017 (onset of symptoms ≤21 years). Outcomes of interest were: alive with no evidence of disease, alive with evidence of disease, and dead of disease. Results: Median age at onset of symptoms was 15.7 years (n = 41; range, 0.2–21 years). Female:male ratio was 3.6: 1. Mixed symptomatology (> 1 hormone abnormality) was the most common presentation (54%, n = 22). Sixty-six percent of patients (n = 27 out of 41) underwent total adrenalectomy. Metastatic disease was more common in children aged > 12 years (p = 0.002 compared to < 4 years). The most common sites of metastases were the liver and lungs. Overall 2-year and 5-year survival rates were 61% (95% CI 45–77) and 46% (95% CI 30–62), respectively. Metastasis at the time of diagnosis was independently associated with poor prognosis (risk ratio 13.7%; 95% CI 3.9–87.7). Weiss criteria (29%) and modified Weiss criteria (33%) were less accurate in younger patients (< 12 years), compared to the Wieneke index (100%). Conclusion: The presence of metastases was an independent prognostic factor. The Wieneke index was the most accurate in predicting clinical outcomes in younger children.

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