Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group

Abstract

Infant acute lymphoblastic leukemia (ALL) has a poor therapeutic outcome despite attempts to treat it based on prognostic factor-guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/ 11q23 rearrangement. All infants enrolled on Children's Cancer Group (CCG) 1953 were tested for MLL rearrangement by Southern blot and the 11q23 translocation partner was identified (4;11, 9;11, 11;19, or "other") by reverse-transcriptase polymerase chain reaction (PCR).One hundred fifteen infants were enrolled; overall event-free survival (EFS) was 41.7% (SD ‫؍‬ 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL-rearranged cases was 33.6% and for MLL-nonrearranged cases was 60.3%. The difference in EFS between the 3 major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age younger than 6 months, and MLL rearrangement,

DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4

“…The eventfree survival of infant ALL is exceptionally low (45-50%), when compared with older children with ALL (B80%). 1,[3][4][5][6] The MLL rearrangement as a first, prenatal leukemogenic event has been elegantly shown to occur in utero by Ford and colleagues. 7 Although the same is true for other types of leukemia, the far shorter latency to leukemia in infant ALL compared with older children, and the exceptionally high concordance rate for ALL in monochorionic twins, 8 indicate that the sole MLL fusion gene could be sufficient for overt leukemia development.…”

A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia

“…12 Furthermore, in clinical studies, etoposide, another DNA-damaging agent, has been shown to have anti-leukemic activity when used in combination with cyclophosphamide and has been incorporated in many protocols for high risk or relapsed ALL. 13,14 We initiated this phase I study to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with etoposide and cyclophosphamide, and to characterize the potential activity and safety of this regimen to treat children with relapsed acute leukemia. 15,16 The phase II portion of the study is currently ongoing.…”

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group

“…1 However, infants with ALL, who represent 2.5-5% of all childhood ALL cases, continue to have high relapse rates and a dismal prognosis, as illustrated by recently published event-free survival (EFS) rates of 22-54%. [2][3][4][5][6][7][8] ALL in infancy has several distinctive clinical characteristics compared with common childhood ALL, including hyperleukocytosis, hepatosplenomegaly, central nervous system (CNS) disease and a high frequency of molecularly evident rearrangement of the MLL gene at chromosome band 11q23. [9][10][11][12] Among these features, MLL gene rearrangement, found in 70-80% of infant ALL cases studied with molecular techniques, is an independent risk factor most predictive of recurrent leukemia.…”