Abstract
Treatment for pediatric acute myeloid leukemia (AML) is highly intensive, and thus almost all patients will experience severe toxicities, which are often life-threatening. In 5–10% of patients, treatment for pediatric AML is fatal. To minimize the adverse effects of treatment, identification and characterization of risk factors for severe toxicity is important. Furthermore, toxic and leukemic responses could be related, and it is likely that toxic response is associated with treatment outcome. The focus of this thesis is to describe the severe toxicities occurring during pediatric AML treatment, investigate potential risk factors and describe prophylactic measures and their safety. In addition, we aimed to investigate how toxicity and risk factors for toxicity are related to treatment outcome.
The studies in the thesis are based on three different cohorts. Study I is based on a cohort of children diagnosed with AML in the five Nordic countries and Hong Kong. For study II, the cohort was expanded to include children diagnosed in the Netherlands, Belgium, Canada, and the USA. The cohort for studies III and IV was the same: Children diagnosed with AML in the Nordic countries, Hong Kong, Belgium, and the Netherlands.
In study I, we found that 90% of children had experienced grade 3–4 toxicities.
Overweight and older age were associated with increased risk of severe toxicity.
In study II, we found no significant differences in risk of relapse and death for four bodymass index (BMI) groups, in contrast to previous reports. Obesity was associated with core binding factor AML.
In study III, we found that time to neutrophil recovery after the first induction course was associated with time to neutrophil recovery after the remaining courses. Furthermore, longer time to neutrophil recovery after the first induction course was associated with increased risk of microbiologically documented infection and increased risk of relapse.
In study IV, we found that use of granulocyte colony-stimulating factor (G-CSF) as
supportive care was frequent in the cohort, but decreased with time. Use of G-CSF was
associated with an increased risk of relapse.
Severe acute toxicities, especially infections, are a large problem in the treatment of
pediatric AML and measures for prevention are limited. The studies in this thesis have
brought further insight into severe toxicities occurring during treatment for pediatric
AML, which will be important knowledge in the attempt to minimize the treatment burden in the future.
The studies in the thesis are based on three different cohorts. Study I is based on a cohort of children diagnosed with AML in the five Nordic countries and Hong Kong. For study II, the cohort was expanded to include children diagnosed in the Netherlands, Belgium, Canada, and the USA. The cohort for studies III and IV was the same: Children diagnosed with AML in the Nordic countries, Hong Kong, Belgium, and the Netherlands.
In study I, we found that 90% of children had experienced grade 3–4 toxicities.
Overweight and older age were associated with increased risk of severe toxicity.
In study II, we found no significant differences in risk of relapse and death for four bodymass index (BMI) groups, in contrast to previous reports. Obesity was associated with core binding factor AML.
In study III, we found that time to neutrophil recovery after the first induction course was associated with time to neutrophil recovery after the remaining courses. Furthermore, longer time to neutrophil recovery after the first induction course was associated with increased risk of microbiologically documented infection and increased risk of relapse.
In study IV, we found that use of granulocyte colony-stimulating factor (G-CSF) as
supportive care was frequent in the cohort, but decreased with time. Use of G-CSF was
associated with an increased risk of relapse.
Severe acute toxicities, especially infections, are a large problem in the treatment of
pediatric AML and measures for prevention are limited. The studies in this thesis have
brought further insight into severe toxicities occurring during treatment for pediatric
AML, which will be important knowledge in the attempt to minimize the treatment burden in the future.
| Translated title of the contribution | Alvorlige bivirkninger under behandlingen for pædiatrisk akut myeloid leukæmi |
|---|---|
| Original language | English |
| Publication status | Published - 9 May 2018 |