Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group
Klein, Kim; van Litsenburg, Raphaële R.L.; de Haas, Valérie; Dors, Natasja; van den Heuvel-Eibrink, Marry M.; Knops, Rutger R.G.; Tissing, Wim J.E.; Versluys, Birgitta A.; Zwaan, C. Michel; Kaspers, Gertjan J.L.
(2020) Pediatric Blood and Cancer, volume 67, issue 4
(Article)
Abstract
Background: With the current more effective treatment regimens for pediatric acute myeloid leukemia (AML), research on early death (ED), treatment-related mortality (TRM), and toxicity becomes increasingly important. The aim of this study was to give an overview of the frequency, clinical features, and risk factors associated with ED and TRM
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in first complete remission (CR1) during the last three consecutive treatment protocols of the Dutch Childhood Oncology Group (DCOG) between 1998 and 2014. Methods: Incidence and risk factors associated with ED and TRM in CR1 were retrospectively studied in 245 patients treated according to the Dutch ANLL-97/AML-12 (n = 118), AML-15 (n = 60), or DB AML-01 (n = 67) protocols. Results: The incidence of ED was, respectively, 5.1%, 6.7%, and 3.0% excluding deaths before treatment (P = NS), and 7.4%, 11.1%, and 4.4% including deaths before the onset of treatment. Severe underweight at initial diagnosis was significantly associated with more frequent ED. When relapse was included as a competing risk, cumulative incidence of death in CR1 were 5.9%, 5.0%, and 4.6% for ANLL97, AML15, and DB01, respectively (P = NS). The most important cause of TRM included infectious and SCT-related complications. Conclusion: We report relatively stable rates of ED and TRM in CR1 in the latest completed DCOG protocols for newly diagnosed AML patients. The most important causes of TRM were SCT- or infection-related, warranting further evaluation and awareness.
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Keywords: Adolescent, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Child, Child, Preschool, Female, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Incidence, Infant, Infant, Newborn, Leukemia, Myeloid, Acute/mortality, Male, Retrospective Studies, Young Adult, Journal Article
ISSN: 1545-5009
Publisher: Wiley-Liss Inc.
Note: Funding Information: —were eligible for inclusion. Written informed consent (IC) by the patient and/or parents/guardians for the use of information for study purposes (normally implemented in the overall IC of the applicable protocols) had to be present. Patients who died prior to IC of the protocol could not be included. However, the number of patients with death before inclusion is registered by the DCOG and was queried separately. Patients with acute promyelocytic leukemia, myeloid leukemia of Down syndrome, or secondary AML were excluded. Patients, aged 0 to 19 years, with AML, newly diagnosed between 1998 and 2014 and participating in one of the following DCOG protocols—ANLL‐97/MRC AML‐12 (ANLL97; 1998‐2002), AML‐15 (AML15; 2002‐2009), DB AML‐01 (DB01; 2009‐2014) After a list with eligible patients was provided by the DCOG, coordinating members of the study team contacted the (at that time) seven treating Dutch pediatric oncology centers. Medical records of all patients eligible for inclusion were reviewed on site by members of the study team between January 2016 and June 2018. Baseline characteristics, treatment details, outcomes, including causes of death, and follow‐up were structurally documented in patient‐specific case report forms. In case of missing baseline data in the chart, the DCOG database was checked to complement the information. Toxicity data and details on the cause of death were collected during initial treatment until the patient had recovered from the last episode of neutropenia, until progression to relapse/refractory treatment, or until the date of allogenic stem cell transplantation (allo‐SCT), if applicable. Causes of death in refractory and/or relapsed patients were registered, but not included in the main analyses of this article. Allo‐SCT‐related death was registered, but details on SCTs were beyond the scope of this study. Response measures and events were adopted from the DCOG database. Follow‐up data with regard to events was collected for all patients until the last date of follow‐up closed to the study visit date or until the date of death. This study was approved by the DCOG's research committee and the Ethical Committee at VU University Medical Center, Amsterdam, the Netherlands. Funding Information: We thank Lynn Ball, a pediatric oncologist, for providing the data of patients treated in Leiden University Hospital. Furthermore, we thank all collaborating pediatric oncologists, research coordinators, and data managers in the participating hospitals for their hospitality, cooperation, and help during this project. We thank all students involved in the data collection during this project and Emily Schwartz, NAF-Fulbright Grant student, for her efforts in optimizing and organizing the database. We thank Birgit Witte, a statistician at VU University, for her help with cumulative incidence analyses. We thank Femke Verwer, a trial coordinator at DCOG, for providing additional/missing data from the DCOG database. Publisher Copyright: © 2019 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.
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