[847] Outcomes for B-Precursor Patients in Legacy Children
s Cancer Group (CCG) and Pediatric Oncology Group (POG) Studies in Childhood Acute Lymphoblastic Leukemia (ALL): A Childrens Oncology Group (COG) Report. Session Type: Poster Session, Board #1-I
Paul S. Gaynon, Bruce C. Camitta, Yousif Matloub, Paul L. Martin, Naomi Winick, Nita L. Seibel, W. Paul Bowman, Harland N. Sather, Meenakshi Devidas, Stephen Hunger, William L. Carroll Childrens Oncology Group, Arcadia, CA, USA
Background: Improved post induction intensification (PII) has led to improved outcome for children with ALL over past decades. The merger of POG and CCG provided an opportunity to compare strategies, specifically, POG: intermediate dose methotrexate (Mtx, 1-2 g/m2) with leucovorin (lv) rescue; CCG: Berlin Frankfurt M
nster (BFM) Protocol Ib and Protocol II (delayed intensification, DI), 
augmented
with additional vincristine (Vcr), escalating-dose parenteral Mtx with no lv rescue, and l-asparaginase (Asp). Methods: Between 1996 and 2005, POG 9904/5/6 trials and CCG 1991/ 1961 trials accrued 6774 B-precursor patients, age > 1 year. NCI standard risk (SR) patients received induction with Vcr, Asp, dexamethasone; NCI higher risk (HR) patients received induction with Vcr, Asp, daunorubicin, and prednisone. POG allocated PII based on age, gender, presenting WBC and the presence or absence of double trisomy 4+10 or t(12;21). CCG allocated PII based on age, presenting WBC, and the Induction Day 7/14 marrow response. POG SR patients without trisomies 4+10 were randomized +/- DI. CCG SR patients received at least one DI. CCG SR slow early response (SER) patients received daunomycin in induction and augmented intensification. ALL CCG HR patients received at least one DI and many received augmented intensification; some POG HR patients received no DI. A subset of POG HR patients, defined by age, gender, and WBC, with very high risk of relapse were designated Pragmatic Very High Risk (VHR) and assigned to a modification of CCG Augmented BFM (Aug BFM, NEJM 1998; 338:1663, see Table). Results: The 5-year EFS was 84
2% (n=1831) and 882% (n=2539) for POG and CCG SR patients (p<0.003). POG and CCG SR patients with double trisomies 4+10 had 5-year EFS of 913% (n=387) with no DI and 953% (n=317) with one or two DIs, respectively. The 5-year EFS was 604% (n=992) and 712% (n=1412) for POG and CCG HR patients (p< 0.001). Results are similar when adjusted for ethnicity. Both SR and HR patients on CCG trials had a statistically significant 25% reduction in risk of an adverse event. Conclusions: This is a non-randomized cross-study comparison. Differences in patient population, treatment assignment, and clinical practice may affect results and interpretation. However, our data suggest the overall superiority of the CCG modified BFM strategy and support the COG decision to build current trials, e.g., AALL0331 and AALL0232, on this platform.
| POG 9904 | POG 9904 | POG 9905 | POG 9906 | CCG 1991 | CCG 1991 | CCG 1961 | CCG 1961 |
| NCI SR | NCI SR | NCI SR + HR | NCI HR | NCI SR | NCI SR | NCI HR | NCI HR |
| Double Trisomy 4 + 10 | t(12;21) | Pragmatic VHR | Day 14 RER | Day 14 SER | Day 7 RER | Day 7 SER | |
| Mtx 1 g versus 2 g/m2 + lv | Mtx 1 g versus 2 g/m2 + lv | Mtx 1 g versus 2 g/m2 + lv | POG Modified Augmented  BFM | Vcr + IV Mtx | Daunomycin rescue | stronger intensification | Augmented BFM |
| DI | DI | Augmented BFM | 10 vs 6 months intensification | Doxo versus Ida/Cpm |
Abstract #847 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Acute Lymphoblastic Leukemia|Children|Adolescents
Disclosure: Research Funding: National Cancer Institute. Honoraria Information: Enzon.
Saturday, December 8, 2007 5:30 PM
Session Info: Poster Session: Acute Lymphocytic Leukemias: Therapy, excluding Transplantation I (5:30 p.m.-7:30 p.m.)