3. OBVIOUS DIFFERENCES Other medical conditions in adults - effects of [subclinical] organ dysfunction on drug disposition Better tolerance in children with ability to deliver repetitive courses more easily (eg. l- aspariginase) Need for more of a focus on long term toxicities in children

6. “BIOLOGIC” ISSUES Cytogenetics - differing incidence of tel/AML, hyperdiploidy, t(9;22) - similar impact of t(4;11), t(8;14) and variants - unknown effect of hypodiploidy, t(1;19) in adults but probably similar (favorable - rare in adults) (unfavorable - much more common in adults)

8. “Nobody does it better” (attributed to James Bond) How about pediatric vs adult oncologists??

9. Outcome of adolescents and young adults with ALL: A comparison of Children’s Cancer Group (CCG) and Cancer and Leukemia Group B regimens [2009]. Stock, Sather, Dodge, Bloomfield, Larson, Nachman for CALGB and CCG.

10. Results in patients aged 16- 21 years CCGCALGB # pts196103 Years1989-951988-98 CR96%93% EFS @ 3 yrs64%38% Median Surv.NR5.2 yrs

11. POSSIBLE EXPLANATIONS Risk factors - groups were very similar except for slightly more pts (10 vs 5%) with t(9;22) or t(4;11) in the CALGB group Regimens Doses delivered Physicians and sites of treatment Differences in:

12. Highly Specific Agents Targeted inhibitors - STI571, antisense Antibodies - anti CD33 Cytotoxics Maybe a bit specific - 506U Plain old new drugs Supportive Care Cytokines Cardioprotectants “Broad” Biologic Activity Antiangiogenesis

13. In some ways this is also a discussion about how to develop therapeutic agents for uncommon (ie economically uninteresting for pharmaceutical companies) disorders. Currently, this is a major issue re the discovery and development of molecularly targeted therapies for hematologic manignancies.

14. PROGNOSTIC FACTORS Age (or stage??) “Leukemia” vs “lymphoma” LDH (or stage??) CNS involvement at diagnosis BUT…… many older patients with ALL and CNS disease are cured

15. RECENT TRIALS IN ADULTS WITH SNCL AND L3 LEUKEMIA nAge (med) OS Comments NCI2025 85% 85% earlier stage French6526 yrs 74% 56% earlier stage German5935 50% all L3 CALGB5444 52% 21% earlier stage MDA2658 49% all L3

16. STI 571 DOSING Should Shaquille O’Neal and Mugsy Bogues receive the same dose simply because they are both old enough to vote?

17. Pediatrics - “Short vs Long” Patte et al JCO 9:123, 1991

18. CALGB 9251