Characteristics and outcome of primary resistant disease in paediatric acute myeloid leukaemia
Lene Karlsson1, Daniel Cheuk2, Barbara De Moerloose3
1Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Nearly 40% of children with resistant acute myeloid leukemia (AML) can be cured with salvage chemotherapy and stem cell transplant. Further chemotherapy beyond two courses did not improve outcomes for resistant AML patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Cancer Biology
Background:
- Resistant disease (RD) is a major cause of treatment failure in pediatric acute myeloid leukemia (AML).
- Understanding risk factors and treatment outcomes for RD is crucial for improving survival rates.
Purpose of the Study:
- To investigate clinical and biological characteristics of pediatric AML patients with resistant disease.
- To evaluate the effectiveness of salvage therapy, including chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), for children with resistant AML.
Main Methods:
- Retrospective analysis of 66 patients with RD from a cohort of 1013 children with AML treated on NOPHO protocols.
- Identification of risk factors for RD, including age and white-blood-cell count at diagnosis.
- Assessment of complete remission (CR) rates and overall survival (OS) following different salvage treatment strategies.
Main Results:
- Older age (≥10 years) and high white-blood-cell count (≥100 × 10^9/L) were identified as risk factors for RD.
- Five-year overall survival (OS) for patients with RD was 38%.
- Salvage chemotherapy achieved CR in 59% of patients, with a significantly improved OS (57%) compared to those not achieving CR (12%).
- Allogeneic HSCT in CR patients resulted in a 56% OS, with an overall OS of 49% for all HSCT recipients.
- Additional chemotherapy courses beyond two did not increase CR rates.
Conclusions:
- Approximately 40% of children with primary resistant AML can achieve long-term survival with salvage therapy and HSCT.
- Early identification of risk factors for RD can aid in treatment planning.
- Treatment strategies should focus on achieving CR with limited salvage chemotherapy courses followed by HSCT for eligible patients.
Abstract:
A significant proportion of events in paediatric acute myeloid leukaemia (AML) are caused by resistant disease (RD). We investigated clinical and biological characteristics in 66 patients with RD from 1013 children with AML registered and treated according to the NOPHO-AML 93, NOPHO-AML 2004, DB AML-01 and NOPHO-DBH AML 2012 protocols. Risk factors for RD were age10 years or older and a white-blood-cell count (WBC) of 100 × 109 /L or more at diagnosis. The five-year overall survival (OS) was 38% (95% confidence interval [CI]: 28%-52%). Of the 63 children that received salvage therapy with chemotherapy, 59% (N = 37) achieved complete remission (CR) with OS 57% (95% CI: 42%-75%) compared to 12% (95% CI: 4%-35%) for children that did not achieve CR. Giving more than two salvage chemotherapy courses did not increase CR rates. OS for all 43 patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) was 49% (95% CI: 36%-66%). Those achieving CR and proceeding to HSCT had an OS of 56% (95% CI: 41%-77%, N = 30). This study showed that almost 40% of children with primary resistant AML can be cured with salvage therapy followed by HSCT. Children that did not achieve CR after two salvage courses with chemotherapy did not benefit from additional chemotherapy.
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