Abstract
The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin–Frankfurt–Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 × 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.
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References
Rivera G, Pinkel D, Simone JV, Hancock ML, Crist WM . Treatment of acute lymphoblastic leukemia. 30 yrs' experience at St Jude Children's Research Hospital. N Engl J Med 1993; 329: 1289–1295.
Van der Does-van den Berg A, Veerman AJP, van Wering ER, de Vries JA, de Waal FC, van Zanen GE et al. Childhood acute lymphoblastic leukemia in the Netherlands. Randomized studies and nationwide treatment results from 1972 to 1995. Int J Ped Hematol Oncol 1998; 52: 125–139.
Van der Does-van den Berg A, van Wering ER, Suciu S, Solbu G, van 't Veer MB, Rammeloo JA et al. Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V). A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG). Am J Pediatr Hematol Oncol 1989; 11: 125–133.
Kamps WA, Veerman AJ, van Wering ER, van Weerden JF, Slater R, van der Does-van den Berg A . Long-term follow-up of Dutch Childhood Leukemia Study Group (DCLSG) protocols for children with acute lymphoblastic leukemia, 1984–1991. Leukemia 2000; 14: 2240–2246.
Veerman AJP, Hählen K, Kamps WA, van Leeuwen EF, de Vaan GAM, Solbu G et al. High cure rate with a moderately intensive treatment regimen in non-high risk childhood acute lymphoblastic leukemia: results of protocol ALL IV from the Dutch Childhood Leukemia Study Group. J Clin Oncol 1996; 14: 911–918.
Reiter A, Schrappe M, Ludwig W, Hiddemann W, Sauter S, Henze G et al. Chemotherapy in 998 unselected childhood ALL patients. Blood 1994; 84: 122–133.
Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig W-D, Henze G et al. Long-term results of four consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 1995. Leukemia 2000; 14: 2205–2222.
Kamps WA, Bökkerink JP, Hählen K, Hermans J, Riehm H, Gadner H et al. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988–1991). Blood 1999; 94: 1226–1236.
Kamps WA, Bökkerink JPM, Hakvoort-Cammel FGAJ, Veerman AJP, Weening RS, van Wering ER et al. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8(1991–1996). Leukemia 2002; 16: 1099–1111.
Veerman AJP, van der Does-van den Berg A, Korbijn CM, van den Berg H, Bökkerink JPM, Bruin MCA et al. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997–2004). Lancet Oncol 2009; 10: 957–966.
Pession A, Valsecchi MG, Masera G, Kamps WA, Magyarosy E, Rizzari C et al. Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukaemia. J Clin Oncol 2005; 23: 7161–7167.
van Dongen JJ, Seriu T, Panzer-Grümayer ER, Biondi A, Pongers-Willemse MJ, Corral L et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 1998; 352: 1731–1738.
Biondi A, Valsecchi MG, Seriu T, D'Aniello E, Willemse MJ, Fasching K et al. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group. Leukemia 2000; 14: 1939–1943.
Groninger E, Meeuwsen-de Boer T, Koopmans P, Uges D, Sluiter W, Veerman A et al. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG). Eur J Cancer 2005; 41: 98–103.
Appel IM, Kazemier KM, Boos J, Lanvers C, Huijmans J, Veerman AJP et al. Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study. Leukemia 2008; 22: 1665–1679.
Appel IM, den Boer ML, Meijerink JPP, Veerman AJP, Reniers NCM, Pieters R . Upregulation of asparagine synthetase expression is not linked to the clinical response to L-asparaginase in pediatric acute lymphoblastic leukemia. Blood 2006; 107: 4244–4249.
De Wreede LC, Fiocco M, Putter H . The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models. www.msbi.nl/multistate (submitted to Computer Methods and Programs in Biomedicine).
Putter H, Fiocco M, Geskus RB . Tutorial in biostatistics: competing risks and multi-state models. Statist Med 2007; 26: 2389–2430.
Gray RJ . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Annal Stat 1988; 16: 1141–1154.
Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather H, D'Angio G . Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Med Pediatr Oncol 1986; 14: 191–194.
Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 1996; 14: 18–24.
Te Poele EM, de Bont ES, Marike Boezen H, Revesz T, Bökkerink JP, Beishuizen A et al. Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment: is the risk of lethal infections too high? Eur J Cancer 2007; 43: 2532–2536.
Jansen NC, Kingma A, Schuitema A, Bouma A, Veerman AJ, Kamps WA . Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia. J Clin Oncol 2008; 26: 3025–3030.
Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M et al. A treatment protocol for infants younger than 1 yr with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet 2007; 370: 240–250.
Dutch Childhood Oncology Group, te Loo DM, Kamps WA, van der Does-van den Berg A, van Wering ER, de Graaf SS . Prognostic significance of blasts in the cerebrospinal fluid without pleiocytosis or a traumatic lumbar puncture in children with acute lymphoblastic leukaemia: experience of the Dutch Childhood Oncology Group. J Clin Oncol 2006; 24: 2332–2336.
Gajjar A, Harrison PL, Sandlund JT, Rivera GK, Ribeiro RC, Rubnitz JE et al. Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia. Blood 2000; 96: 3381–3384.
Bürger B, Zimmermann M, Mann G, Kühl J, Löning L, Riehm H et al. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003; 21: 184–188.
Boudestein K, Kamps WA, Veerman AJP, Pieters R . Different outcomes in older children with acute lymphoblastic leukemia with different treatment protocols in the Netherlands. Submitted.
Acknowledgements
We thank all patients, the physicians participating in the DCOG studies and members of the involved DCLSG Protocol Committees (Bökkerink JPM, Bruin MCA, de Vaan GAM, Hählen K, Hakvoort-Cammel FGAJ, Korthof ET, Schouten TJ, Taminiau JAJM, van den Berg H, van den Heuvel-Eibrink MM, van der Does-van den Berg A, van Leeuwen EF, van Weel-Sipman MH, van Wering ER, Weening RS).
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Kamps, W., van der Pal-de Bruin, K., Veerman, A. et al. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia 24, 309–319 (2010). https://doi.org/10.1038/leu.2009.258
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DOI: https://doi.org/10.1038/leu.2009.258
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