1. ANCO ASH 2005 Review Acute Leukemias Feb 22, 2006 Charles Linker MD

2. Abstract # 43 Mini-allo for AML Herr et al EBMT Review

3. Mini-allo for AML EBMT Registry n = 204 Age 58 (median) Sib and MUD donors Regimen - Flu/Bu, Flu/TBI FU 13mo 1-yr TRM15% 1-yr Rel34% 1-yr LFS50% 1-yr OS 62%

4. Abstract # 47 Mini-allo for AML Shimoni et al Tel Hashomer, Israel

5. Mini-allo AML Israel n = 67 Age > 55 Sib and MUD donors Regimen - Flu/Bu FU 22mo 2-yr TRM 8% 2-yr OS 47% If CR1: 2-yr OS 80%, TRM 0%

6. CALGB 100103 Phase II Study of mini-allo for AML CR1, age > 60 Study Chair: Steve Devine CTN co-chair: Sergio Giralt

7. CALGB 100103 Background - 1 Poor results of chemotherapyPoor results of chemotherapy No signs of progress in chemotherapyNo signs of progress in chemotherapy New approaches are warrantedNew approaches are warranted

8. CALGB 100103 CALGB background data Analysis of 600 CALGB AML age > 60 with cytogeneticsAnalysis of 600 CALGB AML age > 60 with cytogenetics CR 50% 5-year OS 7% !!! Cytogenetics predictive of outcome

9. AML CR1, age > 60 DFS by Cytogenetics < 5 Abnormalities P<0.001  5 Abnormalities

10. AML CR1, age > 60 OS by Cytogenetics

11. AML CR1, age > 60 OS by Age

12. CALGB 100103 Background - 2 Results in best group are still poor (n = 276)Results in best group are still poor (n = 276)CR1 Age 60-75 Receive first consolidation on randomized trial 2-year DFS 24%2-year DFS 24% 3-year DFS 17%3-year DFS 17%

13. CALGB 100103 Eligibility - 1 AML CR1AML CR1 Prior MDS, t-AML allowed < 2 cycles induction < 2 courses consolidation < 6 months in CR1 exclude APL, prior MPD Age 60-74Age 60-74 Matched sibling or 10/10 MUD donorMatched sibling or 10/10 MUD donor

14. CALGB 100103 Eligibility - 2 PS 0 - 2PS 0 - 2 Adequate organ functionAdequate organ function DLCO > 40% EF > 30% Creatinine clearance > 40 Bili < 2.0 AST < 3x normal

15. CALGB 100103 Preparative Regimen Fludarabine 30 mg/m2 x 5days -7 to -3Fludarabine 30 mg/m2 x 5days -7 to -3 Busulfan 0.8 mg/kg IV x 8days -4 to -3Busulfan 0.8 mg/kg IV x 8days -4 to -3 Thymoglobulin 2.5 mg/kg x 3days -4 to -2Thymoglobulin 2.5 mg/kg x 3days -4 to -2 Stem cell infusionday 0Stem cell infusionday 0

16. CALGB 100103 GVH Prophylaxis Tacrolimusday - 2 to +90Tacrolimusday - 2 to +90 MTX 5 mg/m2days, +1, 3, 6, 11MTX 5 mg/m2days, +1, 3, 6, 11 Taper tac day +90 to +150/+180Taper tac day +90 to +150/+180

17. CALGB 100103 Statistics Primary objective 2-year DFS > 35%Primary objective 2-year DFS > 35% 90% power to exclude DFS < 20% Accrual goal = 61Accrual goal = 61 Stopping rules for TRMStopping rules for TRM Assume true TRM 20% Unacceptable TRM 40%

18. CALGB 100103 Currently active in CALGBCurrently active in CALGB sib donors only Amendment in processAmendment in process Add CTN Add MUD

19. Mini-allo for AML, age > 60 Currently treatments work poorlyCurrently treatments work poorly Mini-allo is feasibleMini-allo is feasible Several pilot studies show DFS > 40%Several pilot studies show DFS > 40% Deserves testing in Group settingDeserves testing in Group setting CALGB 100103 is last chance for USA studyCALGB 100103 is last chance for USA study

20. Abstract # 146 Ph+ ALL Dellanoy et al GRALL, France

21. Ph+ ALL,age > 55 Treatment Pre-phasePre-phase Prednisone x 1 week InductionInduction CyDVP Imatinib 600 x 2 mo ConsolidationConsolidation 10 blocks of chemo 2 x 2 mo imatinib CNS-PCNS-P i.t. mtx + cranial RT

22. Ph+ ALL, age > 55 Results N = 30 Age 66 (58 - 78) FU 15mo CR 20/29( vs 6/21 historical control) 1-yr OS 71%(11% control) 1-yr EFS 57%(5% control)

23. ASCT for high-risk ALL Protocol 9501 & SOC

24. Protocol 9501 SOC for Ph+ Effect of Imatinib

25. Ph+ ALL Role of Imatinib Plays major role in inductionPlays major role in induction Safe to combine with chemotherapy Increases remission rate Encouraging results post-remissionEncouraging results post-remission May play role in transplantMay play role in transplant Allo transplant is treatment of first choice Patients get to transplant in remission May reduce relapse rate ASCT being tested in CALGB 10001 May allow PCR neg stem cells for ASCT

26. Abstract # 150 Nelarabine for T-ALL Goekbuget et al GMALL, Germany

27. CALGB 19801 De Angelo et al ASH #743 (2002) Eligibility T-ALL or T-LL Relapse or refractory Treatment Nelarabine (GW 506U) 1.5g/m2 days 1, 3, 5 q3 weeks x 2 cycles Responders may get additional 2 cycles Results 10/38 CR (26%) MDCR 10mo 1-yr DFS 40%

28. Nelarabine Patients and Treatment n = 53 Age 31 (19 - 81) Disease category: First relapse 36 Second relapse 7 Relapse after transplant 7 Refractory 3 Treatment: Nelarabine 1.5g/m2 days 1, 3, 5

29. Nelarabine Results 25/53 CR (47%) 19/25 Cr go to transplant OS 16% OS of CR 27%

30. Nelarabine for T-ALL Important new agentImportant new agent Good choice for relapseGood choice for relapse Should be tested up frontShould be tested up front