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.
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.
Authors: ZoAnn E Dreyer; Joanne M Hilden; Tamekia L Jones; Meenakshi Devidas; Naomi J Winick; Cheryl L Willman; Richard C Harvey; I-Ming Chen; Fred G Behm; Jeanette Pullen; Brent L Wood; Andrew J Carroll; Nyla A Heerema; Carolyn A Felix; Blaine Robinson; Gregory H Reaman; Wanda L Salzer; Stephen P Hunger; William L Carroll; Bruce M Camitta Journal: Pediatr Blood Cancer Date: 2014-11-14 Impact factor: 3.167
Authors: Wanda L Salzer; Tamekia L Jones; Meenakshi Devidas; ZoAnn E Dreyer; Lia Gore; Naomi J Winick; Lillian Sung; Elizabeth Raetz; Mignon L Loh; Cindy Y Wang; Paola De Lorenzo; Maria Grazia Valsecchi; Rob Pieters; William L Carroll; Stephen P Hunger; Joanne M Hilden; Patrick Brown Journal: Pediatr Blood Cancer Date: 2014-11-18 Impact factor: 3.167
Authors: Prakash Satwani; Harland Sather; Fevzi Ozkaynak; Nyla A Heerema; Kirk R Schultz; Jean Sanders; John Kersey; Virginia Davenport; Michael Trigg; Mitchell S Cairo Journal: Biol Blood Marrow Transplant Date: 2007-02 Impact factor: 5.742
Authors: Lynda M Vrooman; Kristen E Stevenson; Jeffrey G Supko; Jane O'Brien; Suzanne E Dahlberg; Barbara L Asselin; Uma H Athale; Luis A Clavell; Kara M Kelly; Jeffery L Kutok; Caroline Laverdière; Steven E Lipshultz; Bruno Michon; Marshall Schorin; Mary V Relling; Harvey J Cohen; Donna S Neuberg; Stephen E Sallan; Lewis B Silverman Journal: J Clin Oncol Date: 2013-01-28 Impact factor: 44.544
Authors: Lynda M Vrooman; Jeffrey G Supko; Donna S Neuberg; Barbara L Asselin; Uma H Athale; Luis Clavell; Kara M Kelly; Caroline Laverdière; Bruno Michon; Marshall Schorin; Harvey J Cohen; Stephen E Sallan; Lewis B Silverman Journal: Pediatr Blood Cancer Date: 2010-02 Impact factor: 3.167
Authors: L B Silverman; K E Stevenson; J E O'Brien; B L Asselin; R D Barr; L Clavell; P D Cole; K M Kelly; C Laverdiere; B Michon; M A Schorin; C L Schwartz; E W O'Holleran; D S Neuberg; H J Cohen; S E Sallan Journal: Leukemia Date: 2009-12-17 Impact factor: 11.528