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Risk stratified treatment for childhood acute lymphoblastic leukaemia: a multicentre observational study from India

Gogoi, M. P.
Das, P.
Das, N.
Das, S.
Narula, G.
Trehan, A.
Bakhshi, S.
Radhakrishnan, V.
Seth, R.
Tembhare, P.
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Abstract
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.
Affiliation
Clinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical Center, Kolkata, West Bengal, 700160, India. Department of Statistics, Bidhannagar College, Kolkata, 700064, India. Department of Pediatric Oncology, Tata Memorial Centre, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India. Homi Bhabha National Institute, Mumbai, Maharashtra, 40094, India. Pediatric Hematology-Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. Department of Medical Oncology, BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India. Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, 600020, India. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India. Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, 410210, India. Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, 110029, India. Department of Oncopathology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, 600020, India. Cytogenetics Department, Tata Medical Center Kolkata, West Bengal, 700160, India. Department of Statistics, University of Calcutta, Kolkata, 700019, India. Department of Paediatric Haematology and Oncology, Tata Medical Center, Kolkata, West Bengal, 700160, India. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M20 4GJ, UK.
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2025
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Gogoi MP, Das P, Das N, Das S, Narula G, Trehan A, et al. Risk stratified treatment for childhood acute lymphoblastic leukaemia: a multicentre observational study from India. The Lancet regional health Southeast Asia. 2025 Jun;37:100593. PubMed PMID: 40487914. Pubmed Central PMCID: PMC12142348. Epub 2025/06/09. eng.
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