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Intensified therapy for infants with acute lymphoblastic leukemia
Author(s) -
Silverman Lewis B.,
McLean Thomas W.,
Gelber Richard D.,
Donnelly Mia J.,
Gilliland D. Gary,
Tarbell Nancy J.,
Sallan Stephen E.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12<2285::aid-cncr10>3.0.co;2-q
Subject(s) - medicine , asymptomatic , pediatrics , incidence (geometry) , pneumonia , leukemia , cytarabine , pneumonitis , lung , physics , optics
BACKGROUND Infants with acute lymphoblastic leukemia (ALL) have a very poor prognosis. Since 1985, we have intensified therapy for infants with ALL by including a month of high dose multiagent chemotherapy after remission induction. METHODS Between 1985 and 1995, we treated 23 infants (age < 12 months). We compared the presenting characteristics and outcomes of these infants with the 11 infants treated on our protocols between 1973 and 1985, an era prior to the intensification of therapy. Available bone marrow samples from infants treated since 1985 were analyzed for the presence of MLL gene rearrangements by Southern blot analyses and for TEL‐AML1 gene fusion by reverse transcriptase‐polymerase chain reaction. RESULTS With a median follow‐up of 5.6 years, the 50‐month event free survival (EFS) (± standard error) for the 23 infants was 54 ± 11%, a significant improvement ( P = 0.001) compared with the outcome for the 11 infants treated on our protocols prior to 1985 (EFS = 9 ± 9%). Of the seven infants found to have a rearranged MLL gene, three (43%) remained in first complete remission. None of the nine infant bone marrow specimens tested had evidence of TEL‐AML1 gene fusion. The intensified therapy was complicated by a high incidence of infections, including septicemia in 52% of patients and Pneumocystis carinii pneumonitis in 22% of patients. Late effects identified in the 13 long term survivors (median age, 6 years) included developmental delay and learning disabilities of varying severity (82% of evaluable patients), asymptomatic cataracts (67%), asymptomatic echocardiographic abnormalities (30%), obesity (27%), and short stature (18%). CONCLUSIONS Intensification of therapy significantly improved the EFS of infants with ALL compared with previous, less intensive regimens and with the experience of other investigators. Future treatment for infants should attempt to improve efficacy while minimizing toxicity. Cancer 1997; 80:2285‐95. © 1997 American Cancer Society.