Seminars in Hematology
Volume 46, Issue 1 , Pages 52-63 , January 2009

Treatment of Childhood Acute Lymphoblastic Leukemia

  • Martin Stanulla
    • ,
  • Martin Schrappe

      Affiliations

    • Corresponding Author InformationAddress correspondence to Martin Schrappe, MD, Children's Hospital at the University Medical Center Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany

References 

  1. Pui CH, Evans WE. Treatment of childhood acute lymphoblastic leukemia. N Engl J Med. 2006;354:166–178
  2. Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL. A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL). Eur J Cancer Care (Engl). 2005;14:53–62
  3. Howard SC, Metzger ML, Wilimas JA, Quintana Y, Pui CH, Robison LL, et al. Childhood cancer epidemiology in low-income countries. Cancer. 2008;112:461–472
  4. Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008;112:416–432
  5. Spix C, Eletr D, Blettner M, Kaatsch P. Temporal trends in the incidence rate of childhood cancer in Germany 1987-2004. Int J Cancer. 2008;122:1859–1867
  6. Swaminathan R, Rama R, Shanta V. Childhood cancers in Chennai, India, 1990-2001: incidence and survival. Int J Cancer. 2008;122:2607–2611
  7. Aricò M, Valsecchi MG, Rizzari C, Barisone E, Biondi A, Casale F, et al. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Münster based chemotherapy. J Clin Oncol. 2008;26:283–289
  8. Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008;111:4477–4489
  9. Gaynon PS, Trigg ME, Heerema NA, Sensel MG, Sather HN, Hammond GD. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia. 2000;14:2223–2233
  10. Harms DO, Janka-Schaub GE. Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia. 2000;14:2234–2239
  11. Kamps WA, Bökkerink JP, Hakvoort-Cammel FG, Veerman AJ, 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
  12. 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
  13. Vilmer E, Suciu S, Ferster A, Bertrand Y, Cavé H, Thyss A, et al. Children Leukemia Cooperative Group Long-term results of three randomized trials (58831, 58832, 58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report. Leukemia. 2000;14:2257–2266
  14. Gustafsson G, Schmiegelow K, Forestier E, Clausen N, Glomstein A, Jonmundsson G, et al. Nordic Society of Pediatric Haematology and Oncology (NOPHO) Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Leukemia. 2000;14:2267–2275
  15. Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital. Blood. 2004;104:2690–2696
  16. Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N, et al. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15. Haematologica. 2008;93:1155–1160
  17. Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO, et al. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL 97 randomized trial. Br J Haematol. 2005;129:734–745
  18. Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig WD, Henze G, et al. Longterm results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Leukemia. 2000;14:2205–2222
  19. Pinkel D. Five year follow-up of “Total Therapy” of childhood lymphocytic leukemia. JAMA. 1971;216:648–652
  20. Riehm H, Gadner H, Henze G, Langermann H-J, Odenwald E. The Berlin childhood acute lymphoblastic leukemia therapy study, 1970-1976. Am J Pediatr Hematol Oncol. 1980;2:299–306
  21. Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007;370:240–250
  22. Jones LK, Saha V. Philadelphia positive acute lymphoblastic leukaemia of childhood. Br J Haematol. 2005;130:489–500
  23. Bennett JM, Catovski D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. French-American-British (FAB) cooperative group Proposals for the classification of the acute leukaemias. Br J Haematol. 1976;33:451–458
  24. Mahmoud HH, Rivera GK, Hancock ML, Krance RA, Kun LE, Behm FG, et al. Low leukocyte counts with blast cells in cerebrospinal fluid of children with newly diagnosed acute lymphoblastic leukemia. N Engl J Med. 1993;329:314–319
  25. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukaemias (European Group for the Immunological Characterisation of Leukaemias (EGIL)). Leukemia. 1995;9:1783–1786
  26. Hiddemann W, Wormann B, Ritter J, Thiel E, Gohde W, Lahme B, et al. Frequency and clinical significance of DNA aneuploidy in acute leukemia. Ann N Y Acad Sci. 1986;468:227–240
  27. Fletcher JA, Lynch EA, Kimball VM, Donnelly M, Tantravahi R, Sallan SE. Translocation t(9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. Blood. 1991;77:435–439
  28. Rubnitz JE, Link MP, Shuster JJ, Carroll AJ, Hakami N, Frankel LS, et al. Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood. 1994;84:570–573
  29. Behm FG, Raimondi SC, Frestedt JL, Liu Q, Crist WM, Downing JR, et al. Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age. Blood. 1996;87:2870–2877
  30. Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Janssen JW, Ratei R, et al. Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL) (A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM 90 and CoALL-05-92). Leukemia. 1996;10:957–963
  31. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, et al Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials (Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group). Blood. 1997;90:571–577
  32. Trka J, Zuna J, Hrusak O, Kalinova M, Muzikova K, Lauschman H, et al. Impact of TEL/AML1-positive patients on age distribution of childhood acute lymphoblastic leukemia in Czech Republic. Leukemia. 1998;12:996–1007
  33. Loh ML, Silverman LB, Young ML, Neuberg D, Golub TR, Sallan SE, et al. Incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia. Blood. 1998;15:4792–4797
  34. Cave H, van der Werff ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J, et al. European Organization for Research and Treatment of Cancer–Childhood Leukemia Cooperative Group (Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia). N Engl J Med. 1998;339:591–598
  35. 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
  36. Foroni L, Harrison JC, Hoffbrand AV, Potter MN. Investigation of minimal residual disease in childhood and adult acute lymphoblastic leukemia by molecular analysis. Br J Haematol. 1999;105:7–24
  37. Ciudad J, San Miguel JF, López-Berges MC, Vidriales B, Valverde B, Ocqueteau M, et al. Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol. 1998;16:3774–3781
  38. Coustan-Smith E, Sancho J, Hancock ML, Boyett JM, Behm FG, Raimondi SC, et al. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood. 2000;96:2691–2696
  39. Dworzak MN, Froschl G, Printz D, Mann G, Pötschger U, Mühlegger N, et al. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood. 2002;99:1952–1958
  40. Nyvold C, Madsen HO, Ryder LP, Seyfarth J, Svejgaard A, Clausen N, et al. Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome. Blood. 2002;99:1253–1258
  41. Brisco MJ, Condon J, Hughes E, Neoh SH, Sykes PJ, Seshadri R, et al. Outcome prediction in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction. Lancet. 1994;343:196–200
  42. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008;111:5477–5485
  43. Flohr T, Schrauder A, Cazzaniga G, Panzer-Grümayer R, van der Velden V, Fischer S, et al. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia. 2008;22:771–782
  44. Pui CH, Williams DL, Raimondi SC, Rivera GK, Look AT, Dodge RK, et al Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia. Blood. 1987;70:247–253
  45. Trueworthy R, Shuster J, Look T, Crist W, Borowitz M, Carroll A, et al. Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol. 1992;10:606–613
  46. Heerema NA, Nachman JB, Sather HN, Sensel MG, Lee MK, Hutchinson R, et al. Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the Childrens' Cancer Group. Blood. 1999;94:4036–4045
  47. Harris MB, Shuster JJ, Carroll A, Look AT, Borowitz MJ, Crist WM, et al. Trisomy of leukemic cells chromosomes 4 and 10 identifies children with B-progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group study. Blood. 1992;79:3316–3324
  48. Nachman JB, Heerema NA, Sather H, Camitta B, Forestier E, Harrison CJ, et al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood. 2007;110:1112–1125
  49. Harbott J, Ritterbach J, Ludwig W-D, Bartram CR, Reiter A, Lampert F. Clinical significance of cytogenetic studies in childhood acute lymphoblastic leukemia: experience of the BFM trials. Recent Results Cancer Res. 1993;131:123–132
  50. Pui CH, Rivera GK, Hancock ML, Raimondi SC, Sandlund JT, Mahmoud HH, et al. Clinical significance of CD10 expression in childhood acute lymphoblastic leukemia. Leukemia. 1993;7:35–40
  51. Ludwig W-D, Harbott J, Bartram CR, Riehm H. Incidence and prognostic significance of immunophenotypic subgroups in childhood acute lymphoblastic leukemia: experience of the BFM study 86. In:  Ludwig W-D,  Thiel E editor. Recent advances in cell biology of acute leukemia: impact on clinical diagnosis and therapy. Berlin: Springer Verlag; 1993;p. 269–282
  52. Pui CH, Boyett JM, Relling MV, Harrison PL, Rivera GK, Behm FG, et al. Sex differences in prognosis for children with acute lymphoblastic leukemia. J Clin Oncol. 1999;17:818–824
  53. 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
  54. Riehm H, Reiter A, Schrappe M, Berthold F, Dopfer R, Gerein V, et al. The in vivo response on corticosteroid therapy as an additional prognostic factor in childhood acute lymphoblastic leukemia (therapy study ALL-BFM 83). Klin Pädiatr. 1987;199:151–160
  55. Gaynon PS, Bleyer WA, Steinherz PG, Finklestein JZ, Littman P, Miller DR, et al. Day 7 marrow response and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features. Med Pediatr Oncol. 1990;18:273–279
  56. Janka-Schaub GE, Stührk H, Kortüm B, Graubner U, Jürgens H, Spaar HJ, et al. Bone marrow blast count at day 28 as the single most important prognostic factor in childhood acute lymphoblastic leukemia. Haematol Blood Transfus. 1992;34:233–237
  57. Arico M, Basso G, Mandelli F, Rizzari C, Colella R, Barisone E, et al. Good steroid response in vivo predicts a favorable outcome in children with T-cell acute lymphoblastic leukemia. Cancer. 1995;75:1684–1693
  58. Gajjar A, Ribeiro R, Hancock ML, Rivera GK, Mahmoud H, Sandlund JT, et al. Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia. Blood. 1995;86:1292–1295
  59. Steinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, et al. Cytoreduction and prognosis in acute lymphoblastic leukaemia—the importance of early marrow response: report from the Childrens Cancer Group. J Clin Oncol. 1996;14:389–398
  60. Tubergen DG, Gilchrist GS, O'Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, et al. Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial. J Clin Oncol. 1993;11:527–537
  61. Kaspers GJ, Veerman AJ, Popp-Snijders C, Lomecky M, Van Zantwijk CH, Swinkels LM, et al. Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia. Med Pediatr Oncol. 1996;27:114–121
  62. Jones B, Freeman AI, Shuster JJ, Jacquillat C, Weil M, Pochedly C, et al. Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia. Med Pediatr Oncol. 1991;19:269–275
  63. Veerman AJ, Hählen K, Kamps WA, Van Leeuwen EF, De Vaan GA, 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 VI from the Dutch Childhood Leukemia Study Group). J Clin Oncol. 1996;14:911–918
  64. 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
  65. Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003;101:3809–3817
  66. Igarashi S, Manabe A, Ohara A, Kumagai M, Saito T, Okimoto Y, et al. No advantage of dexamethasone over prednisolone for the outcome of standard- and intermediate-risk childhood acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group L95-14 protocol. J Clin Oncol. 2005;23:6489–6498
  67. Hurwitz CA, Silverman LB, Schorin MA, Clavell LA, Dalton VK, Glick KM, et al. Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia. Cancer. 2000;88:1964–1969
  68. Waber DP, Carpentieri SC, Klar N, Silverman LB, Schwenn M, Hurwitz CA, et al. Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. J Pediatr Hematol Oncol. 2000;22:206–213
  69. Rizzari C, Valsecchi MG, Aricò M, Conter V, Testi A, Barisone E, et al. Associazione Italiano Ematologia Oncologia Pediatrica (Effect of protracted high-dose L-asparaginase given as a second exposure in a Berlin-Frankfurt-Münster-based treatment: results of the randomized 9102 Intermediate-Risk Childhood Acute Lymphoblastic Leukemia Study–a report from the Associazione Italiana Ematologia Oncologia Pediatrica). J Clin Oncol. 2001;19:1297–1303
  70. 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 leukemia. J Clin Oncol. 2005;23:7161–7167
  71. Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med. 1998;338:1663–1671
  72. Seibel NL, Steinherz PG, Sather HN, Nachman JB, DeLaat C, Ettinger LJ, et al. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008;111:2548–2555
  73. Mattano LA, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group. J Clin Oncol. 2000;18:3262–3272
  74. Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol. 2008;9:257–268
  75. Evans AE, Gilbert ES, Zandstra R. The increasing incidence of central nervous system leukemia in children. Cancer. 1970;26:404–409
  76. Clarke M, Gaynon P, Hann I, Harrison G, Masera G, Peto R, et al. CNS-directed therapy for childhood acute lymphoblastic leukemia: Childhood ALL Collaborative Group overview of 43 randomized trials. J Clin Oncol. 2003;21:1798–1809
  77. Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather HN, 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
  78. Bürger B, Zimmermann M, Mann G, Kühl J, Löning L, Riehm H, et al. Diagnostic cerebrospinal fluid (CSF) examination in children with acute lymphoblastic leukemia (ALL): significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol. 2003;21:184–188
  79. Cario G, Izraeli S, Teichert A, Rhein P, Skokowa J, Möricke A, et al. High interleukin-15 expression characterizes childhood acute lymphoblastic leukemia with involvement of the CNS. J Clin Oncol. 2007;25:4813–4820
  80. Schrauder A, von Stackelberg A, Schrappe M, Cornish J, Peters C. Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials. Bone Marrow Transplant. 2008;41:S71–S74
  81. Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005;366:635–642
  82. Aricò M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med. 2000;342:998–1006
  83. Giverhaug T, Loennechen T, Aarbakke J. Increased concentrations of methylated 6-mercaptopurine metabolites and 6-thioguanine nucleotides in human leukemic cells in vitro by methotrexate. Biochem Pharmacol. 1998;55:1641–1646
  84. Dervieux T, Hancock ML, Evans WE, Pui CH, Relling MV. Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine. Leukemia. 2002;16:209–212
  85. Rivard GE, Infante-Rivard C, Dresse MF, Leclerc JM, Champagne J. Circadian time-dependent response of childhood lymphoblastic leukemia to chemotherapy: a longterm follow-up study of survival. Chronobiol Int. 1993;10:201–204
  86. Schmiegelow K, Glomstein A, Kristinsson J, Salmi T, Schroder H, Bjork O. Impact of morning versus evening schedule for oral methotrexate and 6-mercaptopurine on relapse risk for children with acute lymphoblastic leukemia (Nordic Society for Pediatric Hematology and Oncology (NOPHO)). J Pediatr Hematol Oncol. 1997;19:102–109
  87. Sofianou-Katsoulis A, Khakoo G, Kaczmarski R. Reduction in bioavailability of 6-mercaptopurine on simultaneous administration with cow's milk. Pediatr Hematol Oncol. 2006;23:485–487
  88. Relling MV, Hancock ML, Boyett JM, Pui CH, Evans WE. Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia. Blood. 1999;93:2817–2823
  89. Conter V, Valsecchi MG, Silvestri D, Campbell M, Dibar E, Magyarosy E, et al. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007;369:123–131
  90. Childhood ALL Collaborative Group. Duration and intensity of maintenance chemotherapy in acute lymphoblastic leukaemia: overview of 42 trials involving 12 000 randomised children. Lancet. 1996;347:1783–1788
  91. Harms DO, Göbel U, Spaar HJ, Graubner UB, Jorch N, Gutjahr P, et al. Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92. Blood. 2003;102:2736–2740
  92. Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SB, Lilleyman J, et al. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet. 2006;368:1339–1348
  93. Stork LC, Sather H, Hutchinson RJ, Broxson EH, Matloub Y, Yanofsky R, et al. Comparison of mercaptopurine (MP) with thioguanine (TG) and IT methotrexate (ITM) with IT “triples” (ITT) in children with SR-ALL: results of CCG-1952 [abstract]. Blood. 2002;100:156a
  94. Henze G, Fengler R, Hartmann R. Chemotherapy for relapsed childhood acute lymphoblastic leukemia: results of the BFM Study Group. Haematol Blood Transfus. 1994;36:374–379
  95. Gaynon PS, Qu RP, Chappell RJ, Willoughby ML, Tubergen DG, Steinherz PG, et al. Survival after relapse in childhood acute lymphoblastic leukemia: impact of site and time to first relapse: the Children's Cancer Group experience. Cancer. 1998;82:1387–1395
  96. Wheeler K, Richards S, Bailey C, Gibson B, Hann IM, Hill FG, et al. Comparison of bone marrow transplant and chemotherapy for relapsed childhood acute lymphoblastic leukaemia: the MRC UKALL X experience: Medical Research Council Working Party on Childhood Leukaemia. Br J Haematol. 1998;101:94–103
  97. Borgmann A, von Stackelberg A, Hartmann R, Ebell W, Klingebiel T, Peters C, et al. Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: a matched-pair analysis. Blood. 2003;101:3835–3839
  98. Eapen M, Raetz E, Zhang M, Muehlenbein C, Devidas M, Abshire T, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood. 2006;107:4961–4967
  99. Eckert C, Biondi A, Seeger K, Cazzaniga G, Hartmann R, Beyermann B, et al. Prognostic value of minimal residual disease in relapsed childhood acute lymphoblastic leukaemia. Lancet. 2001;358:1239–1241
  100. Mody R, Li S, Dover DC, Sallan S, Leisenring W, Oeffinger KC, et al Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood. 2008;111:5515–5523
  101. Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, Hester AL, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol. 2004;22:4979–4990

 Supported by the Deutsche Krebshilfe, the Bundesministerium für Bildung und Forschung, the Madeleine Schickedanz Kinderkrebsstiftung, and the Deutsche José Carreras-Leukämie-Stiftung.

PII: S0037-1963(08)00150-9

doi: 10.1053/j.seminhematol.2008.09.007

Seminars in Hematology
Volume 46, Issue 1 , Pages 52-63 , January 2009

Article Tools

* Image Usage & Resolution