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Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999
J M Chessells1, C J Harrison, S L Watson
1Molecular Haematology Unit, Camelia Botnar Laboratories, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. j.chessels@ich.ucl.ac.uk
Insights
Infant 92 protocol improved survival for infants with acute lymphoblastic leukemia (ALL) compared to Infant 87. While high-dose therapy and bone marrow transplantation showed no added benefit, younger age and CNS involvement remained poor prognostic factors.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Infants with acute lymphoblastic leukemia (ALL) have a historically poor prognosis.
- Intensive treatment strategies are crucial for improving outcomes in this high-risk group.
Purpose of the Study:
- To evaluate the efficacy of two consecutive treatment protocols (Infant 87 and Infant 92) in improving survival rates for infants with ALL.
- To identify prognostic factors influencing treatment outcomes in infant ALL.
Main Methods:
- A comparative study of 126 infants with ALL treated on Infant 87 (n=40) and Infant 92 (n=86) protocols.
- Both protocols included intensive induction, consolidation, and central nervous system (CNS) protection.
- Infant 92 incorporated modified intensification therapy and allowed high-dose chemotherapy with bone marrow transplantation (BMT) in first remission.
Main Results:
- The Infant 92 protocol demonstrated superior 4-year event-free survival (33%) and overall survival (46%) compared to Infant 87 (22.5% and 32.5%, respectively).
- A significant reduction in remission deaths was observed in the Infant 92 cohort.
- Multivariate analysis identified younger age, CNS involvement at diagnosis, and high initial leukocyte count as adverse prognostic factors.
- Cytogenetic analysis in Infant 92 revealed frequent 11q23 rearrangements (67%), including t(4;11) translocation (39%), but no significant survival difference between cytogenetic subgroups was found.
Conclusions:
- The Infant 92 protocol significantly improved survival outcomes for infants with ALL, largely due to reduced remission deaths.
- While high-dose therapy and BMT in first remission did not enhance survival in this study, younger age and CNS involvement remain critical adverse prognostic indicators.
- The contribution of unfavorable cytogenetics to the poor prognosis of infant ALL requires further investigation, and the role of intensified therapy and BMT needs continued evaluation.
Abstract:
One hundred and twenty-six infants with acute lymphoblastic leukaemia (ALL) were treated on two consecutive protocols, Infant 87 (n = 40) and Infant 92 (n = 86), in an attempt to improve the poor prognosis of this disease. Both included intensive induction and consolidation with intrathecal and high-dose systemic therapy for central nervous system (CNS) protection. Intensification therapy was modified and high-dose chemotherapy with bone marrow transplantation in first remission was permitted in Infant 92. Four-year event-free survival was superior in Infant 92 (33%; 95% CI 23-44%) compared with Infant 87 (22.5%; 95% CI 12-37%) (P = 0.04) and survival at 4 years was also superior, 46% (95% CI 35-57%) c.f. 32.5% (95% CI 20-48%) (P = 0.01), largely as a result of a significant reduction in remission deaths. Twelve patients in Infant 92 underwent bone marrow transplantation (BMT) in first remission, but their survival was no better than that of patients receiving chemotherapy. Multivariate analysis of prognostic factors showed the adverse influence of younger age, CNS involvement at diagnosis and a high initial leucocyte count, but not of CD10 expression. Cytogenetic analysis, available in 93% of patients in Infant 92, showed that 67% had chromosomal rearrangements involving 11q23 of which 39% had the translocation t(4;11) (q21;q23). There was no significant difference in event-free survival between cytogenetic subgroups, although no children under 6 months of age with 11q23 abnormalities, other than the t(4;11), survived. In conclusion, infants with lymphoblastic leukaemia remain a high-risk group, but it is unclear whether their adverse prognosis can be attributed to unfavourable cytogenetics alone. The role of high-dose therapy and BMT in first remission remains uncertain.
