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11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia
C H Pui1, F G Behm, J R Downing
1Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101-0318.
Insights
Infant acute lymphoblastic leukemia (ALL) with 11q23/MLL rearrangement has a poor prognosis. This genetic abnormality is an independent predictor of adverse events in infant ALL cases.
Area of Science:
- Pediatric Oncology
- Hematology
- Molecular Genetics
Background:
- Infant acute lymphoblastic leukemia (ALL) presents unique challenges due to its poor prognosis compared to childhood ALL.
- Identifying specific adverse prognostic factors is crucial for developing targeted treatment strategies.
Purpose of the Study:
- To analyze leukemic cell characteristics in infants under 1 year with ALL.
- To determine adverse prognostic factors contributing to the poor outcomes in this specific patient group.
Main Methods:
- Analysis of treatment outcomes in 30 infants with ALL treated between 1979 and 1993.
- Utilized a stepwise multivariate regression model to identify key prognostic indicators for event-free survival.
Main Results:
- High presenting leukocyte count, CNS leukemia, CD10- phenotype, myeloid-associated antigen expression, and 11q23/MLL rearrangement were common in infant ALL.
- 11q23/MLL rearrangement was significantly correlated with younger age, CD10- phenotype, myeloid antigen expression, and high leukocyte count.
- Rearranged 11q23/MLL independently predicted a worse prognosis, with a 4.7-fold increased risk of adverse events.
Conclusions:
- 11q23/MLL rearrangement defines a high-risk subgroup of infant ALL requiring novel therapeutic approaches.
- Infants without 11q23/MLL abnormality have an intermediate prognosis and can be managed with risk-directed protocols.
Purpose:
Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group.
Patients And Methods:
Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival.
Results:
Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants.
Conclusion:
The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.