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Acute Leukemias

Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985–2000)

Abstract

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20–30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0–18 years were treated on four consecutive protocols: 85-01 (1985–1987), 87-01 (1987–1991), 91-01 (1991–1955) and 95-01 (1996–2000). The 10-year event-free survival (EFS)±s.e. by protocol was 77.9±2.8% (85-01), 74.2±2.3% (87-01), 80.8±2.1% (91-01) and 80.5±1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79–85% for T-cell ALL patients and 75–78% for adolescents (age 10–18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

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References

  1. Sallan SE, Cammita BM, Cassady JR, Nathan DG, Frei IIIrd E . Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. Blood 1978; 51: 425–433.

    CAS  Google Scholar 

  2. Sallan SE, Hitchcock-Bryan S, Gelber R, Cassady JR, Frei IIIrd E, Nathan DG . Influence of intensive asparaginase in the treatment of childhood non-T- cell acute lymphoblastic leukemia. Cancer Res 1983; 43: 5601–5607.

    CAS  Google Scholar 

  3. Clavell LA, Gelber RD, Cohen HJ, Hitchcock-Bryan S, Cassady JR, Tarbell NJ et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med 1986; 315: 657–663.

    Article  CAS  Google Scholar 

  4. Schorin MA, Blattner S, Gelber RD, Tarbell NJ, Donnelly M, Dalton V et al. Treatment of childhood acute lymphoblastic leukemia: results of Dana- Farber Cancer Institute/Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01. J Clin Oncol 1994; 12: 740–747.

    Article  CAS  Google Scholar 

  5. LeClerc JM, Billett AL, Gelber RD, Dalton V, Tarbell N, Lipton JM et al. Treatment of childhood acute lymphoblastic leukemia: results of Dana- Farber ALL Consortium Protocol 87-01. J Clin Oncol 2002; 20: 237–246.

    Article  Google Scholar 

  6. Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001; 97: 1211–1218.

    Article  CAS  Google Scholar 

  7. Moghrabi A, Levy DE, Asselin B, Barr R, Clavell L, Hurwitz C et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood 2007; 109: 896–904.

    Article  CAS  Google Scholar 

  8. Silverman LB, McLean TW, Gelber RD, Donnelly MJ, Gilliland DG, Tarbell NJ et al. Intensified therapy for infants with acute lymphoblastic leukemia: results from the Dana-Farber Cancer Institute Consortium. Cancer 1997; 80: 2285–2295.

    Article  CAS  Google Scholar 

  9. Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ . Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol 1993; 11: 1780–1786.

    Article  CAS  Google Scholar 

  10. Asselin BL, Kreissman S, Coppola DJ, Bernal SD, Leavitt PR, Gelber RD et al. Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1999; 21: 6–12.

    Article  CAS  Google Scholar 

  11. Schwartz CL, Thompson EB, Gelber RD, Young ML, Chilton D, Cohen HJ et al. Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia. J Clin Oncol 2001; 19: 1040–1046.

    Article  CAS  Google Scholar 

  12. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  13. Cox DR, Oates D . Regression models and life tables. J Royal Stat Soc 1972; B34: 187–220.

    Google Scholar 

  14. Klabfleisch JD, Prentice RL . The Statistical Analysis of Failure Time Data. Wiley: New York, 1980.

  15. Gray RJ . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  16. Zhou J, Goldwasser MA, Li A, Dahlberg SE, Neuberg D, Wang H et al. Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01. Blood 2007; 110: 1607–1611.

    Article  CAS  Google Scholar 

  17. Loh ML, Goldwasser MA, Silverman LB, Poon WM, Vattikuti S, Cardoso A et al. Prospective analysis of TEL/AML1 positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01. Blood 2006; 107: 4508–4513.

    Article  CAS  Google Scholar 

  18. Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L et al. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol 2003; 21: 3616–3622.

    Article  Google Scholar 

  19. Barry E, DeAngelo DJ, Neuberg D, Stevenson K, Loh ML, Asselin BL et al. Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols. J Clin Oncol 2007; 25: 813–819.

    Article  CAS  Google Scholar 

  20. DeAngelo DJ, Dahlberg S, Silverman LB, Couban S, Amrein PC, Deftel MD et al. A multicenter Phase II study using a dose intensified pediatric regimen in adults with untreated acute lymphoblastic leukemia. Blood 2007; 110: 181a.

    Google Scholar 

  21. Lipshultz SE, Giantris AL, Lipsitz SR, Kimball Dalton V, Asselin BL, Barr RD et al. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol 2002; 20: 1677–1682.

    Article  CAS  Google Scholar 

  22. Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR et al. Dexrazoxane reduces myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia: results from a randomized trial. N Engl J Med 2004; 351: 145–153.

    Article  CAS  Google Scholar 

  23. Barry EV, Vrooman LM, Dahlberg SE, Neuberg DS, Asselin BL, Athale UH et al. Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J Clin Oncol 2008; 26: 1106–1111.

    Article  CAS  Google Scholar 

  24. Waber DP, Turek J, Catania L, Stevenson K, Robaey P, Romero I et al. Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. J Clin Oncol 2007; 25: 4914–4921.

    Article  CAS  Google Scholar 

  25. Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG et al. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 2007; 297: 1207–1215.

    Article  CAS  Google Scholar 

  26. Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002; 30: 41–47.

    Article  CAS  Google Scholar 

  27. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002; 1: 75–87.

    Article  CAS  Google Scholar 

  28. Dulucq S, St-Onge G, Gagne V, Ansari M, Sinnett D, Labuda D et al. DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL. Blood 2008; 111: 3692–3700.

    Article  CAS  Google Scholar 

  29. Armstrong SA, Kung AL, Mabon ME, Silverman LB, Stam RW, Den Boer ML et al. Inhibition of FLT3 in MLL Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 2003; 3: 173–183.

    Article  CAS  Google Scholar 

  30. Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, Letai A . BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood 2008; 111: 2300–2309.

    Article  CAS  Google Scholar 

  31. Wei G, Twomey D, Lamb J, Schlis K, Agarwal J, Stam RW et al. Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance. Cancer Cell 2006; 10: 331–342.

    Article  CAS  Google Scholar 

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Acknowledgements

These trials were supported in part by a grant from the National Institute of Health (NCI Grant 5P01CA068484). We thank the patients, families, physicians, nurses, clinical research coordinators and all others who participated in these trials. We acknowledge the important contributions of Jennifer Cronin, Annette Dalton, Virginia Dalton, Meghan Eaton and Richard D Gelber.

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Correspondence to L B Silverman.

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Silverman, L., Stevenson, K., O'Brien, J. et al. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985–2000). Leukemia 24, 320–334 (2010). https://doi.org/10.1038/leu.2009.253

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