Trausti Oskarsson1,2, Stefan Söderhäll1,2, Johan Arvidson3, Erik Forestier4, Thomas Leth Frandsen5, Marit Hellebostad6, Päivi Lähteenmäki7, Ólafur G Jónsson8, Ida Hed Myrberg2, Mats Heyman1,2. 1. Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden. 2. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. 3. Department of Pediatric Oncology, Uppsala University Hospital, Uppsala, Sweden. 4. Department of Medical Biosciences, Umeå University, Umeå, Sweden. 5. Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. 6. Department of Pediatrics, Drammen Hospital, Drammen, Norway. 7. Department of Pediatrics, Turku University Hospital and Turku University, Turku, Finland. 8. Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
Abstract
BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes. CONCLUSIONS: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.
BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes. CONCLUSIONS: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.
Authors: Patrick A Brown; Lingyun Ji; Xinxin Xu; Meenakshi Devidas; Laura E Hogan; Michael J Borowitz; Elizabeth A Raetz; Gerhard Zugmaier; Elad Sharon; Melanie B Bernhardt; Stephanie A Terezakis; Lia Gore; James A Whitlock; Michael A Pulsipher; Stephen P Hunger; Mignon L Loh Journal: JAMA Date: 2021-03-02 Impact factor: 56.272
Authors: Allison Barz Leahy; Caitlin W Elgarten; Stephan A Grupp; Shannon L Maude; David T Teachey Journal: Expert Rev Anticancer Ther Date: 2018-10 Impact factor: 3.627