Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia

D J DeAngelo, K E Stevenson, S E Dahlberg, L B Silverman, S Couban, J G Supko, P C Amrein, K K Ballen, M D Seftel, A R Turner, B Leber, K Howson-Jan, K Kelly, S Cohen, J H Matthews, L Savoie, M Wadleigh, L A Sirulnik, I Galinsky, D S Neuberg, S E Sallan, R M Stone, D J DeAngelo, K E Stevenson, S E Dahlberg, L B Silverman, S Couban, J G Supko, P C Amrein, K K Ballen, M D Seftel, A R Turner, B Leber, K Howson-Jan, K Kelly, S Cohen, J H Matthews, L Savoie, M Wadleigh, L A Sirulnik, I Galinsky, D S Neuberg, S E Sallan, R M Stone

Abstract

On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.

Figures

Figure 1
Figure 1
DFCI ALL Consortium Protocol flow diagram. One hundred patients with newly diagnosed ALL were enrolled. Ninety-two patients were considered eligible, of whom 78 (85%) achieved a complete remission within 1 month. Fifty-seven were evaluable for the asparaginase feasibility end point. All 92 patients were evaluable for analysis of EFS and OS.
Figure 2
Figure 2
(a and b) represent the OS for 92 eligible patients and DFS for 78 patients who achieved a CR, respectively. With a median follow-up of 4.5 years, the 4-year OS for all 92 patients on protocol was 67% (95% CI; 56–76%) and the 4-year DFS was 69% (95% CI; 56–78%) for the 78 patients who achieved a CR. The solid lines represent the Kaplan–Meier estimates, and the dashed lines represent the 95% confidence bands about those estimates. (c and d) Represent OS and DFS by immunophenotype and Philadelphia chromosome status, respectively.
Figure 3
Figure 3
(a and b) Median asparaginase dose and nadir serim asparaginase activity during the 30-week Consolidation Course. Error bars extend to the 25th and 75th percentiles.

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