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[Acute lymphoblastic leukemia in infancy: results of 5 multicenter ALL-BFM therapy studies 1970-1986]
Insights
Infant acute lymphoblastic leukemia (ALL) has a poor prognosis due to more frequent unfavorable subtypes, characterized by high tumor burden and central nervous system (CNS) involvement. However, improved treatment strategies significantly enhance remission rates in infant ALL patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Leukemia Research
Background:
- Infantile acute lymphoblastic leukemia (ALL) presents a less favorable prognosis compared to other age groups.
- Understanding the biological and clinical factors contributing to this outcome is crucial for improving infant ALL treatment.
- Previous clinical trials (ALL-BFM 1970-1986) provide a retrospective data set for analysis.
Purpose of the Study:
- To retrospectively evaluate clinical and biological features of infant patients (≤2 years) in five ALL-BFM trials (1970-1986).
- To identify causes and biological principles behind the impaired outcome in infant ALL.
- To assess the impact of treatment advancements on remission probabilities.
Main Methods:
- Retrospective analysis of 196 infant patients (≤2 years) with ALL, including 42 infants under 1 year.
- Evaluation of clinical characteristics such as tumor burden and central nervous system (CNS) involvement.
- Assessment of biological features including leukemic blast cell immunophenotype (cALLa, Tdt).
Main Results:
- Unfavorable childhood ALL subtypes are more prevalent in infants, particularly those under six months, correlating with poor prognosis.
- These unfavorable subtypes are associated with large tumor burden, initial CNS involvement, and higher CNS relapse rates.
- Undifferentiated leukemic blast cells often exhibit negative cALLa and Tdt reactions (0-ALL, AUL).
Conclusions:
- The increased frequency of prognostically unfavorable ALL subtypes in infants, especially those under six months, explains their poorer outcomes.
- While treatment failures do not appear to influence the poorer outcome, advancements in trials ALL-BFM 81 and ALL-BFM 83 significantly improved the probability of continuous complete remission (pCCR) for infant patients.
- Treatment itself is a major prognostic determinant in managing infant ALL.
Abstract:
Acute lymphoblastic leukemia (ALL) of infancy has in contrast to all other age groups a less favorable prognosis. In order to determine the possible causes and biological principles for impaired outcome of infant patients in five consecutive clinical trials ALL-BFM 1970-1986, both clinical characteristics and biological features for one hundred and ninety-six patients aged two years and less have been evaluated retrospectively (forty-two infants under one year of age). The observations illustrate, that less favorable subtypes of childhood ALL are more frequent in these children, preferably in infants aged six months and less, explaining decisively the impaired prognosis. These subtypes are characterized by large tumor burden (p = less than 0.001), initial central nervous system (CNS) involvement (p = less than 0.001), and a high CNS relapse rate (p = 0.03). Phenotypically the undifferentiated leukemic blast cells show negative reactions for cALLa and often for Tdt (0-ALL and AUL; p = less than 0.001). The switch to prognostically more favorable ALL subtypes occurs about the end of the first year of life. Nevertheless, early failures by non-response or late-response seem not to influence the poorer outcome. However, compared to the preceding trials, results of studies ALL-BFM 81 and ALL-BFM 83 were significantly improved in respect to the probability of continuous complete remission for infant patients (pCCR less than 1 y: 0.44 vs. 0.28), confirming that treatment by itself is one of the major prognostic determinants.