Risk stratified treatment for childhood acute lymphoblastic leukaemia: a multicentre observational study from India
Manash Pratim Gogoi1, Parag Das1, Nandana Das1
1Clinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical Center, Kolkata, West Bengal, 700160, India.
Insights
Childhood acute lymphoblastic leukaemia (ALL) survival rates in India improved significantly with risk-stratified treatment protocols. Standardizing genetic and measurable residual disease (MRD) testing can further enhance outcomes for pediatric ALL patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Childhood acute lymphoblastic leukemia (ALL) survival rates in high-income countries approach 90%, but outcomes in India were significantly lower (~65%) despite similar treatment protocols.
- This highlights a critical disparity in pediatric cancer care that requires investigation and targeted interventions.
Purpose of the Study:
- To evaluate the effectiveness of a risk-stratified treatment approach using genetics and measurable residual disease (MRD) for B-cell precursor (BCP) ALL in India.
- To compare outcomes between standard-risk (SR), intermediate-risk (IR), and high-risk (HR) BCP-ALL, and uniformly treated T-cell ALL (T-ALL) patients.
Main Methods:
- The Indian Childhood Collaborative Leukaemia (ICiCLe) group enrolled 2695 children (aged 1-18 years) between January 2013 and May 2018.
- Patients were categorized into SR, IR, and HR groups based on genetics and MRD levels, receiving tailored therapy intensities. T-ALL patients received uniform treatment.
- Data on risk stratification, deaths, and relapses were collected annually.
Main Results:
- Four-year event-free survival ranged from 61% in HR to 76% in SR BCP-ALL, and overall survival ranged from 73% in HR to 88% in SR.
- T-ALL patients had a 4-year overall survival of 77%. Induction deaths were significantly lower in SR patients.
- Significant variations in treatment-related deaths (2-13%) and relapses (21-45%) were observed across centers, correlating with differences in MRD levels and time to relapse.
Conclusions:
- Risk-stratified, reduced-intensity treatment protocols, coupled with collaborative efforts, demonstrably decrease treatment-related deaths and relapses in pediatric ALL.
- Standardization of genetic and MRD testing across all treatment centers, alongside improved access to high-quality medications, is crucial for further enhancing survival rates in childhood ALL.
Background:
Overall survival rates of children with acute lymphoblastic leukaemia (ALL) in high-income countries approach 90%. Treated on the same protocols, outcomes in India, were ∼65%.
Methods:
The Indian Childhood Collaborative Leukaemia (ICiCLe) group used genetics and measurable residual disease (MRD) to categorise B-cell precursor (BCP) ALL as standard (SR), intermediate (IR) and high-risk (HR) to receive increasing intensity of therapy. T-ALL were treated uniformly. Data on risk stratification, deaths and relapses were collected annually.
Findings:
2695 patients aged 1-18 years were enrolled between January 2013 and May 2018. Induction deaths were significantly lower in SR patients (p = 0·002) compared to others. At a median 61 (59-62) months, the 4-year event free and overall survival was 76% (72-79%) and 88% (85-90%) in SR; 70% (66-74%) and 80% (77-83%) in IR; 61% (51-64%) and 73% (70-76%) in HR; and 69% (62-75%) and 77% (70-83%) in T-ALL patients (p < 0·0001). For BCP-ALL, regression analyses showed age, white cell count, bulky disease, high risk genetics and treating centre as independent prognostic variables. The cumulative incidence of treatment deaths (TRD) and relapses at centres varied from 2% (1-5) to 13% (10-17) (p ≤ 0·0001); and 21% (17-26) to 45% (39-51) (p ≤ 0·0001) respectively with significant differences in proportion of BCP-ALL patients with MRD ≥ 0·01% (p = 0·0007) and time to relapse (p = 0·0001).
Interpretation:
Risk stratified directed reduced intensity treatment and collaboration decreases treatment deaths and relapses. Standardisation of genetic and MRD tests across centres and access to high quality drugs will lead to further improvements in survival.
Funding:
DBT-Wellcome; UKIERI, TCS Foundation.
