Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Author:

Schilstra Clarissa E.,McCleary Karen,Fardell Joanna E.,Donoghoe Mark W.,McCormack Emma,Kotecha Rishi S.,Lourenco Richard De Abreu,Ramachandran Shanti,Cockcroft Ruelleyn,Conyers Rachel,Cross Siobhan,Dalla-Pozza Luciano,Downie Peter,Revesz Tamas,Osborn Michael,Alvaro Frank,Wakefield Claire E.,Marshall Glenn M.,Mateos Marion K.,Trahair Toby N.

Abstract

Abstract Background Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children’s Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children’s general and cancer-related health-related quality of life (HRQoL) and parents’ emotional well-being. Methods Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1–213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children’s HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL.

Funder

Kids Cancer Alliance

Kids to Adults (K2A) Clinical Academic Group, Australia

Sydney Partnership for Health, Education, Research & Enterprise

Research Training Program Scholarship, Australia

The Kids Cancer Project, Australia

National Health and Medical Research Council

Children’s Leukaemia and Cancer Research Foundation

Cancer Council New South Wales

Estate of the Late Harry McPaul

Kids with Cancer Foundation

Anthony Rothe Memorial Trust, Australia

Cancer Institute NSW, Australia

Royal Australasian College of Physicians, Australia

Cancer Therapeutics CRC, Australia

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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