Interfant 99 - treatment reflecting unique biology of the infant acute lymphoblastic leukemia. The results in the Czech Republic
Abstract
Acute lymphoblastic leukemia (ALL) affecting infants is a rare malignancy with the biological behavior different from the leukemia of older children. About 80% infants have a rearrangement of the MLL gene at the chromosomal locus 11q23.
The most frequent abnormality is the t(4;11)(q21;q23) translocation producing the MLL-AF4 fusion gene. The MLL+ ALL originates usually in the immature B-cell precursors with aberrant expression of myeloid antigens.
It is characterized by hyperleukocytosis, poor initial treatment response and high risk of the early relapse. Treatment results are significantly worse than in older children.
Current protocols usually combine elements used in the therapy of both lymphoid and myeloid acute leukemias. Between 1990 and 1999, twenty-one infants were diagnosed with ALL in the Czech Republic and only 6 of them were treated according to a protocol designed specifically for the infants.
Five-years event-free survival (EFS) was 33 %, only one out of the ten children with MLL-AF4 fusion gene was cured. Between 2000 and 2005, fourteen infants were diagnosed with ALL and 13 of them were treated in the international randomized study Interfant 99.
Ten children bear an MLL rearrangement, most frequently the t(4;11) in 6 of them. Flow cytometry showed pro-B ALL immunophenotype in nine patients, pre-B ALL in two cases and two children were diagnosed as T-ALL (unusual in the infant age) with complex karyotype.
Ten children had WBC >= 50 000/μl, 7 infants were younger than 6 months at diagnosis. Twelve children achieved complete remission.
Two children with a poor early treatment response were stratified into the high risk group, all others into the standard risk group. Seven children suffered from relapse and one child developed secondary malignancy.
Altogether, 7 children are alive, four of them in the first remission. Five children underwent 7 stem cell transplantations from the unrelated (n = 6) or HLA identical donor (n = 1) (only one of them in the first remission).
Five-years EFS of 482 patients enrolled in the international study Interfant 99 is 46% and overall survival 55% showing the improvement in comparison with majority of the previous studies.