Skip to main content
SpringerLink
Log in

Treatment of Relapsed Acute Lymphoblastic Leukemia

Perspective 2

  • Chapter
Treatment of Acute Leukemias

Part of the book series: Current Clinical Oncology ((CCO))

  • 181 Accesses

Abstract

Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in childhood. With currently used treatment, event-free survival rates (EFS) range from 70 to 75%. However, relapse of ALL remains the fourth most frequent diagnosis in childhood cancer, with an incidence ranging close to that of neuroblastoma (1,2). Compared with the prognosis for newly diagnosed ALL, the chance of long-term survival is substantially reduced in cases of relapse. The remission rate is limited by a higher rate of induction deaths owing to reduced tolerance to treatment after organ-toxic frontline therapy. Furthermore, the rate of nonresponses to treatment is increased, since blast cells surviving the intensive front line treatment have had the chance to develop resistance toward commonly used antileukemic drugs. Even if a complete remission (CR) can be achieved, the rate of subsequent relapses is high.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Henze G. Chemotherapy for relapsed childhood acute lymphoblastic leukemia. Int J Pediatr Hematol Oncol 1997;5:199–213.

    Google Scholar 

  2. Gaynon PS, Qu RP, Chappell RJ, 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.

    Article  PubMed  CAS  Google Scholar 

  3. Bene MC, Bernier M, Castoldi G, et al. Impact of immunophenotyping on management of acute leukemias. Haematologica 1999;84:1024–1034.

    PubMed  CAS  Google Scholar 

  4. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976;33:451–458.

    Article  PubMed  CAS  Google Scholar 

  5. Löffler H, Gassmann W. Morphology and cytochemistry of acute lymphoblastic leukaemia. Baillieres Clin Haematol 1994;7: 263–272.

    Article  PubMed  Google Scholar 

  6. Hayhoe FG. Cytochemistry of the acute leukaemias. Histochem J 1984;16:1051–1059.

    Article  PubMed  CAS  Google Scholar 

  7. Look AT, Roberson PK, Williams DL, et al. Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia. Blood 1985;65:1079–1086.

    PubMed  CAS  Google Scholar 

  8. Raimondi SC, Pui CH, Head DR, Rivera GK, Behm FG. Cytogenetically different leukemic clones at relapse of childhood acute lymphoblastic leukemia. Blood 1993;82:576–580.

    PubMed  CAS  Google Scholar 

  9. Heerema NA, Palmer CG, Weetman R, Bertolone S. Cytogenetic analysis in relapsed childhood acute lymphoblastic leukemia. Leukemia 1992;6:185–192.

    PubMed  CAS  Google Scholar 

  10. Steward CG, Goulden NJ, Katz F, et al. A polymerase chain reaction study of the stability of Ig heavy-chain and T-cell receptor delta gene rearrangements between presentation and relapse of childhood B-lineage acute lymphoblastic leukemia. Blood 1994; 83:1355–1362.

    PubMed  CAS  Google Scholar 

  11. Beyermann B, Adams HP, Henze G. Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia: a matched-pair analysis. Berlin-Frankfurt-Münster Study Group. J Clin Oncol 1997;15:2231–2237.

    PubMed  CAS  Google Scholar 

  12. Seeger K, Adams HP, Buchwald D, et al. TEL-AML1 fusion transcript in relapsed childhood acute lymphoblastic leukemia. The Berlin-Frankfurt-Münster Study Group. Blood 1998;91: 1716–1722.

    PubMed  CAS  Google Scholar 

  13. Goulden N, Langlands K, Steward C, et al. PCR assessment of bone marrow status in ‘isolated’ extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia. Br J Haematol 1994;87:282–285.

    Article  PubMed  CAS  Google Scholar 

  14. Uckun FM, Gaynon PS, Stram DO, et al. Paucity of leukemic progenitor cells in the bone marrow of pediatric B-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse. Clin Cancer Res 1999;5:2415–2420.

    PubMed  CAS  Google Scholar 

  15. Wolfrom C, Hartmann R, Brühmüller S, et al. Similar outcome on boys with isolated and combined testicular acute lymphoblastic leukemia relapse after stratified BFM salvage therapy. Haematol Blood Transfus 1997;38:647–651.

    Google Scholar 

  16. Bührer C, Hartmann R, Fengler R, et al. Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia. Med Pediatr Oncol 1993;21:470–476.

    Article  PubMed  Google Scholar 

  17. Ritchey AK, Pollock BH, Lauer SJ, Andejeski Y, Buchanan GR. Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study. J Clin Oncol 1999;17:3745–3752.

    PubMed  CAS  Google Scholar 

  18. Bekassy AN, Kullendorff CM, Arnbjornsson E. Elective testicular biopsy at the end of maintenance treatment for acute lymphoblastic leukemia. A prospective study. Eur J Pediatr Surg 1992;2:352–354.

    Article  PubMed  CAS  Google Scholar 

  19. Nachman J, Palmer NF, Sather HN, et al. Open-wedge testicular biopsy in childhood acute lymphoblastic leukemia after two years of maintenance therapy: diagnostic accuracy and influence on outcome-a report from Children’s Cancer Study Group. Blood 1990;75:1051–1055.

    PubMed  CAS  Google Scholar 

  20. Miller DR, Leikin SL, Albo VC, et al. The prognostic value of testicular biopsy in childhood acute lymphoblastic leukemia: a report from the Children’s Cancer Study Group. J Clin Oncol 1990;8:57–66.

    PubMed  CAS  Google Scholar 

  21. Wofford MM, Smith SD, Shuster JJ, et al. Treatment of occult or late overt testicular relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Clin Oncol 1992; 10:624–630.

    PubMed  CAS  Google Scholar 

  22. Abshire TC, Buchanan GR, Jackson JF, et al. Morphologic, immunologic and cytogenetic studies in children with acute lymphoblastic leukemia at diagnosis and relapse: a Pediatric Oncology Group study. Leukemia 1992;6:357–362.

    PubMed  CAS  Google Scholar 

  23. Lilleyman JS, Stevens RF, Hann IM, et al. Changes in cytomorphology of childhood lymphoblastic leukaemia at the time of disease relapse. Childhood Leukaemia Working Party of the United Kingdom Medical Research Council. J Clin Pathol 1995; 48:1051–1053.

    Article  PubMed  CAS  Google Scholar 

  24. van Wering ER, Beishuizen A, Roeffen ET, et al. Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia. Leukemia 1995;9: 1523–1533.

    PubMed  Google Scholar 

  25. Guglielmi C, Cordone I, Boecklin F, et al. Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications. Leukemia 1997;11: 1501–1507.

    Article  PubMed  CAS  Google Scholar 

  26. Taylor JJ, Rowe D, Kylefjord H, et al. Characterisation of nonconcordance in the T-cell receptor gamma chain genes at presentation and clinical relapse in acute lymphoblastic leukemia. Leukemia 1994;8:60–66.

    PubMed  CAS  Google Scholar 

  27. Stankovic T, Mann JR, Darbyshire PJ, Taylor AM. Clonal diversity, measured by heterogeneity of Ig and TCR gene rearrangements, in some acute leukaemias of childhood is associated with a more aggressive disease. Eur J Cancer 1995;3:394–401.

    Article  Google Scholar 

  28. Davi F, Gocke C, Smith S, Sklar J. Lymphocytic progenitor cell origin and clonal evolution of human B-lineage acute lymphoblastic leukemia. Blood 1996;88:609–621.

    PubMed  CAS  Google Scholar 

  29. Green E, McConville CM, Powell JE, et al. Clonal diversity of Ig and T-cell-receptor gene rearrangements identifies a subset of childhood B-precursor acute lymphoblastic leukemia with increased risk of relapse. Blood 1998;92:952–958.

    PubMed  CAS  Google Scholar 

  30. Rosenquist R, Thunberg U, Li AH, et al. Clonal evolution as judged by immunoglobulin heavy chain gene rearrangements in relapsing precursor-B acute lymphoblastic leukemia. Eur J Haematol 1999;63:171–179.

    Article  PubMed  CAS  Google Scholar 

  31. Vora A, Frost L, Goodeve A, et al. Late relapsing childhood lymphoblastic leukemia. Blood 1998;92:2334–2337.

    PubMed  CAS  Google Scholar 

  32. Lo Nigro L, Cazzaniga G, Di Cataldo A, et al. Clonal stability in children with acute lymphoblastic leukemia (ALL) who relapsed five or more years after diagnosis. Leukemia 1999;13:190–195.

    Article  PubMed  Google Scholar 

  33. Chessells JM, Leiper AD, Richards SM. A second course of treatment for childhood acute lymphoblastic leukaemia: long-term follow-up is needed to assess results. Br J Haematol 1994;86:48–54.

    Article  PubMed  CAS  Google Scholar 

  34. Miniero R, Saracco P, Pastore G, et al. Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology-Oncology (AIEOP). Med Pediatr Oncol 1995;24:71–76.

    Article  PubMed  CAS  Google Scholar 

  35. Rivera GK, Hudson MM, Liu Q, et al. Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia. Blood 1996;88:831–837.

    PubMed  CAS  Google Scholar 

  36. Henze G, Fengler R, Hartmann R, et al. Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM Group. Blood 1991;78:1166–1172.

    PubMed  CAS  Google Scholar 

  37. Schroeder H, Garwicz S, Kristinsson J, et al. Outcome after first relapse in children with acute lymphoblastic leukemia: a population-based study of 315 patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO). Med Pediatr Oncol 1995;25:372–378.

    Article  PubMed  CAS  Google Scholar 

  38. Wheeler K, Richards S, Bailey C, Chessells J. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Kuo AH, Yataganas X, Galicich JH, Fried J, Clarkson BD. Proliferative kinetics of central nervous system (CNS) leukemia. Cancer 1975;36:232–239.

    Article  PubMed  CAS  Google Scholar 

  40. Tsuchiya J, Moteki M, Shimano S, et al. Proliferative kinetics of the leukemic cells in meningeal leukemia. Cancer 1978;42:1255–1262.

    Article  PubMed  CAS  Google Scholar 

  41. Jahnukainen K, Saari T, Salmi TT, Pollanen P, Pelliniemi LJ. Reactions of Leydig cells and blood vessels to lymphoblastic leukemia in the rat testis. Leukemia 1995;9:908–914.

    PubMed  CAS  Google Scholar 

  42. Buchanan GR, Boyett JM, Pollock BH, et al. Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology Group study. Cancer 1991;68:48–55.

    Article  PubMed  CAS  Google Scholar 

  43. Winick NJ, Smith SD, Shuster J, et al. Treatment of CNS relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Clin Oncol 1993;11:271–278.

    PubMed  CAS  Google Scholar 

  44. Ribeiro RC, Rivera GK, Hudson M, et al. An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia. J Clin Oncol 1995;13:333–338.

    PubMed  CAS  Google Scholar 

  45. Neale GA, Pui CH, Mahmoud HH, et al. Molecular evidence for minimal residual bone marrow disease in children with ‘isolated’ extra-medullary relapse of T-cell acute lymphoblastic leukemia. Leukemia 1994;8:768–775.

    PubMed  CAS  Google Scholar 

  46. Lal A, Kwan E, al Mahr M, et al. Molecular detection of acute lymphoblastic leukaemia in boys with testicular relapse. Mol Pathol 1998;51:277–281.

    Article  PubMed  CAS  Google Scholar 

  47. Chessells JM. Relapsed lymphoblastic leukaemia in children: a continuing challenge. Br J Haematol 1998;102:423–438.

    Article  PubMed  CAS  Google Scholar 

  48. Jahnukainen K, Salmi TT, Kristinsson J, et al. The clinical indications for identical pathogenesis of isolated and non-isolated testicular relapses in acute lymphoblastic leukaemia. Acta Paediatr 1998;87:638–643.

    Article  PubMed  CAS  Google Scholar 

  49. Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995;9:1783–1786.

    PubMed  CAS  Google Scholar 

  50. Baruchel A, Cayuela JM, Ballerini P, et al. The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts. Br J Haematol 1997;99:101–106.

    Article  PubMed  CAS  Google Scholar 

  51. Henze G, Fengler R, Hartmann R, et al. Chemotherapy for bone marrow relapse of childhood acute lymphoblastic leukemia. Cancer Chemother Pharmacol 1989;24:S16–19.

    Article  PubMed  Google Scholar 

  52. Bührer C, Hartmann R, Fengler R, et al. Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. J Clin Oncol 1996;14:2812–2817.

    PubMed  Google Scholar 

  53. Crist W, Carroll A, Shuster J, et al. Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study. Blood 1990;76:489–494.

    PubMed  CAS  Google Scholar 

  54. Schlieben S, Borkhardt A, Reinisch I, 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.

    PubMed  CAS  Google Scholar 

  55. Fletcher JA, Lynch EA, Kimball VM, et al. Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. Blood 1991;77: 435–439.

    PubMed  CAS  Google Scholar 

  56. Rubnitz JE, Pui CH. Childhood acute lymphoblastic leukemia. Oncologist 1997;2:374–380.

    PubMed  Google Scholar 

  57. Uckun FM, Nachman JB, Sather HN, et al. Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: a report from the Children’s Cancer Group. Cancer 1998;83: 2030–2039.

    Article  PubMed  CAS  Google Scholar 

  58. Schrappe M, Arico M, Harbott J, et al. Philadelphia chromosomepositive (Ph+) childhood acute lymphoblastic leukemia: good initial steroid response allows early prediction of a favorable treatment outcome. Blood 1998;92:2730–2741.

    PubMed  CAS  Google Scholar 

  59. Borkhardt A, Cazzaniga G, Viehmann S, 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-Münster Study Group. Blood 1997;90:571–577.

    PubMed  CAS  Google Scholar 

  60. Takahashi Y, Horibe K, Kiyoi H, et al. Prognostic significance of TEL/AML1 fusion transcript in childhood B-precursor acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1998;20:190–195.

    Article  PubMed  CAS  Google Scholar 

  61. Rubnitz JE, Downing JR, Pui CH, et al. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol 1997;15:1150–1157.

    PubMed  CAS  Google Scholar 

  62. Loh ML, Silverman LB, Young ML, et al. Incidence of TEL/AML1 fusion in children with relapsed acute lymphoblastic leukemia. Blood 1998;92:4792–4797.

    PubMed  CAS  Google Scholar 

  63. Rubnitz JE, Behm FG, Wichlan D, et al. Low frequency of TEL-AML1 in relapsed acute lymphoblastic leukemia supports a favorable prognosis for this genetic subgroup. Leukemia 1999;13:19–21.

    Article  PubMed  CAS  Google Scholar 

  64. Seeger K, Buchwald D, Peter A, et al. TEL-AMLI fusion in relapsed childhood acute lymphoblastic leukemia. Blood 1999;94:374–376.

    PubMed  CAS  Google Scholar 

  65. Seeger K, Buchwald D, Taube T, et al. TEL-AML1 positivity in relapsed B cell precursor acute lymphoblastic leukemia in childhood. Berlin-Frankfurt-Münster Study Group [letter]. Leukemia 1999;13:1469–1470.

    Article  PubMed  CAS  Google Scholar 

  66. Langlands K, Craig JI, Anthony RS, Parker AC. Clonal selection in acute lymphoblastic leukaemia demonstrated by polymerase chain reaction analysis of immunoglobulin heavy chain and T-cell receptor delta chain rearrangements. Leukemia 1993;7:1066–1070.

    PubMed  CAS  Google Scholar 

  67. Klumper E, Pieters R, Veerman AJ, et al. In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia. Blood 1995;86:3861–3868.

    PubMed  CAS  Google Scholar 

  68. Dhooge C, De Moerloose B. Clinical significance of P-glycoprotein (P-gp) expression in childhood acute lymphoblastic leukemia. Results of a 6-year prospective study. Adv Exp Med Biol 1999;457:11–19.

    Article  PubMed  CAS  Google Scholar 

  69. Dhooge C, De Moerloose B, Laureys G, et al. P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study. Br J Haematol 1999;105:676–683.

    Article  PubMed  CAS  Google Scholar 

  70. Ivy SP, Olshefski RS, Taylor BJ, et al. Correlation of P-glycoprotein expression and function in childhood acute leukemia: a Children’s Cancer Group study. Blood 1996;88:309–318.

    PubMed  CAS  Google Scholar 

  71. Miniero R, Massara FM, Saroglia EM, et al. Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study. Minerva Pediatr 1994;46:463–470.

    PubMed  CAS  Google Scholar 

  72. den Boer ML, Pieters R, Kazemier KM, et al. The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. Leukemia 1998;12:912–920.

    Article  CAS  Google Scholar 

  73. Goasguen JE, Lamy T, Bergeron C, et al. Multifactorial drug-resistance phenomenon in acute leukemias: impact of P 170-MDR 1, LRP56 protein, glutathione-transferases and metallothionein systems on clinical outcome. Leuk Lymphoma 1996;23:567–576.

    Article  PubMed  CAS  Google Scholar 

  74. Trippett T, Schlemmer S, Elisseyeff Y, et al. Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia. Blood 1992;80:1158–1162.

    PubMed  CAS  Google Scholar 

  75. Matherly LH, Taub JW. Methotrexate pharmacology and resistance in childhood acute lymphoblastic leukemia. Leuk Lymphoma 1996:21:359–368.

    Article  PubMed  CAS  Google Scholar 

  76. Goker E, Waltham M, Kheradpour A, et al. Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations. Blood 1995;86:677–684.

    PubMed  CAS  Google Scholar 

  77. Matherly LH, Taub JW, Ravindranath Y, et al. Elevated dihydrofolate reductase and impaired methotrexate transport as elements in methotrexate resistance in childhood acute lymphoblastic leukemia. Blood 1995;85:500–509.

    PubMed  CAS  Google Scholar 

  78. Rots MG, Pieters R, Peters GJ, et al. Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Blood 1999;93:1677–1683.

    PubMed  CAS  Google Scholar 

  79. Rots MG, Pieters R, Kaspers GJ, et al. Differential methotrexate resistance in childhood T- versus common/preB- acute lymphoblastic leukemia can be measured by an in situ thymidylate synthase inhibition assay, but not by the MTT assay. Blood 1999;93: 1067–1074.

    PubMed  CAS  Google Scholar 

  80. Lacerda JF, Goker E, Kheradpour A, et al. Selective treatment of SCID mice bearing methotrexate-transport-resistant human acute lymphoblastic leukemia tumors with trimetrexate and leucovorin protection. Blood 1995;85:2675–2679.

    PubMed  CAS  Google Scholar 

  81. Rots MG, Pieters R, Peters GJ, et al. Circumvention of methotrexate resistance in childhood leukemia subtypes by rationally designed antifolates. Blood 1999;94:3121–3128.

    PubMed  CAS  Google Scholar 

  82. Mauritz R, Bekkenk MW, Rots MG, et al. Ex vivo activity of methotrexate versus novel antifolate inhibitors of dihydrofolate reductase and thymidylate synthase against childhood leukemia cells. Clin Cancer Res 1998;4:2399–2410.

    PubMed  CAS  Google Scholar 

  83. Yeargin J, Haas M. Elevated levels of wild-type p53 induced by radiolabeling of cells leads to apoptosis or sustained growth arrest. Curr Biol 1995;5:423–431.

    Article  PubMed  CAS  Google Scholar 

  84. Kawamura M, Kikuchi A, Kobayashi S, et al. Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia. Blood 1995;85:2546–2552.

    PubMed  CAS  Google Scholar 

  85. Zhou M, Yeager AM, Smith SD, Findley HW. Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53gene. Blood 1995;85:1608–1614.

    PubMed  CAS  Google Scholar 

  86. Marks DI, Kurz BW, Link MP, et al. Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia. J Clin Oncol 1997;15:1158–1162.

    PubMed  CAS  Google Scholar 

  87. Lam V, McPherson JP, Salmena L, et al. p53 gene status and chemosensitivity of childhood acute lymphoblastic leukemia cells to Adriamycin. Leuk Res 1999;23:871–880.

    Article  PubMed  CAS  Google Scholar 

  88. Zhou M, Gu L, Abshire TC, et al. Incidence and prognostic significance of MDM2 oncoprotein overexpression in relapsed childhood acute lymphoblastic leukemia. Leukemia 2000;14:61–67.

    Article  PubMed  CAS  Google Scholar 

  89. Blau O, Avigad S, Stark B, et al. Exon 5 mutations in the p53 gene in relapsed childhood acute lymphoblastic leukemia. Leuk Res 1997;21:721–729.

    Article  PubMed  CAS  Google Scholar 

  90. Coustan-Smith E, Kitanaka A, Pui CH, et al. Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia. Blood 1996;87:1140–1146.

    PubMed  CAS  Google Scholar 

  91. Tsurusawa M, Saeki K, Katano N, Fujimoto T. Bcl-2 expression and prognosis in childhood acute leukemia. Children’s Cancer and Leukemia Study Group. Pediatr Hematol Oncol 1998;15:143–155.

    Article  PubMed  CAS  Google Scholar 

  92. Hogarth LA, Hall AG. Increased BAX expression is associated with an increased risk of relapse in childhood acute lymphocytic leukemia. Blood 1999;93:2671–2678.

    PubMed  CAS  Google Scholar 

  93. Srinivas G, Kusumakumary P, Nair MK, Panicker KR, Pillai MR. Mutant p53 protein, Bcl-2/Bax ratios and apoptosis in paediatric acute lymphoblastic leukaemia. J Cancer Res Clin Oncol 2000; 126:62–67.

    Article  PubMed  CAS  Google Scholar 

  94. Kaspers GJ, Pieters R, Klumper E, De Waal FC, Veerman AJ. Glucocorticoid resistance in childhood leukemia. Leuk Lymphoma 1994;13:187–201.

    Article  PubMed  CAS  Google Scholar 

  95. Dörffel W, Hartmann R, Schober S, et al. Drug resistance testing as a basis for tailored therapy in children with refractory or relapsed acute lymphoblastic leukemia. In: Drug Resistance in Leukemia and Lymphoma. (Kaspers GJ, Pieters R, Twentyman PR, Weisenthal LM, Veerman AJ, eds.), Chur: Harwood, 1993; pp. 353–357.

    Google Scholar 

  96. Henze G, Agthe AG, Neuendank A, et al. Tailored therapy for relapsed or refractory childhood acute lymphoblastic leukemia. Leukemia 1995;9:538.

    Google Scholar 

  97. Rivera G, Pratt CB, Aur RJ, Verzosa M, Hustu HO. Recurrent childhood lymphocytic leukemia following cessation of therapy: treatment and response. Cancer 1976;37:1679–1686.

    Article  PubMed  CAS  Google Scholar 

  98. Cornbleet MA, Chessells JM. Bone-marrow relapse in acute lymphoblastic leukaemia in childhood. BMJ 1978;2:104–106.

    Article  PubMed  CAS  Google Scholar 

  99. Creutzig U, Schellong G. Treatment of relapse in acute lymphoblastic leukaemia of childhood. Dtsch Med Wochenschr 1980; 105:1109–1112.

    Article  PubMed  CAS  Google Scholar 

  100. Behrendt H, van Leeuwen EF, Schuwirth C, et al. Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia. Med Pediatr Oncol 1990;18:190–196.

    Article  PubMed  CAS  Google Scholar 

  101. Johnson FL, Thomas ED, Clark BS, et al. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med 1981;305:846–851.

    Article  PubMed  CAS  Google Scholar 

  102. Woods WG, Nesbit ME, Ramsay NK, et al. Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factors (a report from the University of Minnesota Bone Marrow Transplantation Team). Blood 1983; 61:1182–1189.

    PubMed  CAS  Google Scholar 

  103. Buchanan GR. Diagnosis and management of relapse in acute lymphoblastic leukemia. Hematol Oncol Clin North Am 1990;4: 971–995.

    PubMed  CAS  Google Scholar 

  104. Giona F, Testi AM, Rondelli R, et al. ALL R-87 protocol in the treatment of children with acute lymphoblastic leukaemia in early bone marrow relapse. Br J Haematol 1997;99:671–677.

    Article  PubMed  CAS  Google Scholar 

  105. 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.

    Google Scholar 

  106. Pui CH, Bowman WP, Ochs J, Dodge RK, Rivera GK. Cyclic combination chemotherapy for acute lymphoblastic leukemia recurring after elective cessation of therapy. Med Pediatr Oncol 1988;16:21–26.

    Article  PubMed  CAS  Google Scholar 

  107. Sadowitz PD, Smith SD, Shuster J, et al. Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1993;81:602–609.

    PubMed  CAS  Google Scholar 

  108. Culbert SJ, Shuster JJ, Land VJ, et al. Remission induction and continuation therapy in children with their first relapse of acute lymphoid leukemia. A Pediatric Oncology Group study. Cancer 1991;67:37–42.

    Article  PubMed  CAS  Google Scholar 

  109. Rivera GK, Buchanan G, Boyett JM, et al. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group study. N Engl J Med 1986;315:273–278.

    Article  PubMed  CAS  Google Scholar 

  110. Morland BJ, Shaw PJ. Induction toxicity of a modified Memorial Sloan-Kettering-New York II Protocol in children with relapsed acute lymphoblastic leukemia: a single institution study. Med Pediatr Oncol 1996;27:139–144.

    Article  PubMed  CAS  Google Scholar 

  111. Rossi MR, Masera G, Zurlo MG, et al. Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 1986; 3:1–9.

    Article  PubMed  CAS  Google Scholar 

  112. Buchanan GR, Rivera GK, Boyett JM, et al. Reinduction therapy in 297 children with acute lymphoblastic leukemia in first bone marrow relapse: a Pediatric Oncology Group study. Blood 1988; 72:1286–1292.

    PubMed  CAS  Google Scholar 

  113. Hryniuk WM. The importance of dose intensity in the outcome of chemotherapy. Important Adv Oncol 1988:121–141.

    Google Scholar 

  114. Hartmann R, Hubalek D, Fengler R, Henze G. Impact of early treatment intensity on outcome after first relapse of childhood ALL. Ann Hematol 1995;70 (suppl 2):A132.

    Google Scholar 

  115. Buchanan GR, Rivera GK, Pollock BH, et al. Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group study. Cancer 2000;88:1166–1174.

    Article  PubMed  CAS  Google Scholar 

  116. Bührer C, Hartmann R, Fengler R, et al. Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. Blood 1994;83: 3468–3472.

    PubMed  Google Scholar 

  117. Feig SA, Ames MM, Sather HN, et al. Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children’s Cancer Group. Med Pediatr Oncol 1996; 27:505–514.

    Article  PubMed  CAS  Google Scholar 

  118. Neuendank A, Hartmann R, Bührer C, et al. Acute toxicity and effectiveness of idarubicin in childhood acute lymphoblastic leukemia. Eur J Haematol 1997;58:326–332.

    Article  PubMed  CAS  Google Scholar 

  119. Wolfrom C, Hartmann R, Fengler R, et al. Randomized comparison of 36-hour intermediate-dose versus 4-hour high- dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia. J Clin Oncol 1993;11:827–833.

    PubMed  CAS  Google Scholar 

  120. Henze G, Fengler R, Hartmann R, et al. High dose versus intermediate dose MTX for relapsed childhood ALL: interim results of the randomized multicentric trial ALL-REZ BFM 90. Med Pediatr Oncol 1994;23:190.

    Google Scholar 

  121. Evans AE, Gilbert ES, Zandstra R. The increasing incidence of central nervous system leukemia in children (Children’s Cancer Study Group A). Cancer 1970;26:404–409.

    Article  PubMed  CAS  Google Scholar 

  122. Ortega JA, Nesbit ME, Sather HN, et al. Long-term evaluation of a CNS prophylaxis trial—treatment comparisons and outcome after CNS relapse in childhood ALL: a report from the Children’s Cancer Study Group. J Clin Oncol 1987;5:1646–1654.

    PubMed  CAS  Google Scholar 

  123. George SL, Ochs JJ, Mauer AM, Simone JV. The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia. J Clin Oncol 1985;3:776–781.

    PubMed  CAS  Google Scholar 

  124. Behrendt H, van Leeuwen EF, Schuwirth C, et al. The significance of an isolated central nervous system relapse, occurring as first relapse in children with acute lymphoblastic leukemia. Cancer 1989;63:2066–2072.

    Article  PubMed  CAS  Google Scholar 

  125. Willoughby ML. Treatment of overt meningeal leukaemia in children: results of second MRC meningeal leukaemia trial. BMJ 1976;1:864–867.

    Article  PubMed  CAS  Google Scholar 

  126. Land VJ, Thomas PR, Boyett JM, et al. Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A Pediatric Oncology Group study. Cancer 1985;56:81–87.

    Article  PubMed  CAS  Google Scholar 

  127. Mandell LR, Steinherz P, Fuks Z. Delayed central nervous system (CNS) radiation in childhood CNS acute lymphoblastic leukemia. Results of a pilot trial. Cancer 1990;66:447–450.

    Article  PubMed  CAS  Google Scholar 

  128. Stackelberg A, Hartmann R, Ritter J, et al. Male gender as an independent adverse risk factor for children with isolated CNS relapse of ALL. In: Israeli-German Bi-National Conference: Current Concepts in Pediatric Hematology-Oncology. January 26–29, Eilat, Israel, Abstr vol 1999; p.21.

    Google Scholar 

  129. Bleyer WA, Sather H, Hammond GD. Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin’s lymphoma: 1985. A report from the Children’s Cancer Study Group. Cancer 1986;58:590–594.

    Article  PubMed  CAS  Google Scholar 

  130. Ortega JJ, Javier G, Toran N. Testicular infiltrates in children with acute lymphoblastic leukemia: a prospective study. Med Pediatr Oncol 1984;12:386–393.

    Article  PubMed  CAS  Google Scholar 

  131. Sullivan MP, Perez CA, Herson J, et al. Radiotherapy (2500 rad) for testicular leukemia: local control and subsequent clinical events: a Southwest Oncology Group study. Cancer 1980;46:508–515.

    Article  PubMed  CAS  Google Scholar 

  132. Bowman WP, Aur RJ, Hustu HO, Rivera G. Isolated testicular relapse in acute lymphocytic leukemia of childhood: categories and influence on survival. J Clin Oncol 1984;2:924–929.

    PubMed  CAS  Google Scholar 

  133. Atkinson K, Thomas PR, Peckham MJ, McElwain TJ. Radiosensitivity of the acute leukaemic infiltrate. Eur J Cancer 1976;12: 535–540.

    PubMed  CAS  Google Scholar 

  134. Grundy RG, Leiper AD, Stanhope R, Chessells JM. Survival and endocrine outcome after testicular relapse in acute lymphoblastic leukaemia. Arch Dis Child 1997;76:190–196.

    Article  PubMed  CAS  Google Scholar 

  135. Uderzo C, Grazia Zurlo M, Adamoli L, et al. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. J Clin Oncol 1990;8:672–677.

    PubMed  CAS  Google Scholar 

  136. Brecher ML, Weinberg V, Boyett JM, et al. Intermediate dose methotrexate in childhood acute lymphoblastic leukemia resulting in decreased incidence of testicular relapse. Cancer 1986; 58:1024–1028.

    Article  PubMed  CAS  Google Scholar 

  137. Freeman AI, Weinberg V, Brecher ML, et al. Comparison of intermediate-dose methotrexate with cranial irradiation for the postinduction treatment of acute lymphocytic leukemia in children. N Engl J Med 1983;308:477–484.

    Article  PubMed  CAS  Google Scholar 

  138. Leiper AD, Grant DB, Chessells JM. Gonadal function after testicular radiation for acute lymphoblastic leukaemia. Arch Dis Child 1986;61:53–56.

    Article  PubMed  CAS  Google Scholar 

  139. Castillo LA, Craft AW, Kernahan J, Evans RG, Aynsley-Green A. Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukaemia. Med Pediatr Oncol 1990;18: 185–189.

    Article  PubMed  CAS  Google Scholar 

  140. Askin FB, Land VJ, Sullivan MP, et al. Occult testicular leukemia: testicular biopsy at three years continuous complete remission of childhood leukemia: a Southwest Oncology Group study. Cancer 1981;47:470–475.

    Article  PubMed  CAS  Google Scholar 

  141. Storb R, Bryant JI, Buckner CD, et al. Allogeneic marrow grafting for acute lymphoblastic leukemia: leukemic relapse. Transplant Proc 1973;5:923–926.

    PubMed  CAS  Google Scholar 

  142. Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 1977;49: 511–533.

    PubMed  CAS  Google Scholar 

  143. Brochstein JA, Kernan NA, Groshen S, et al. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 1987;317:1618–1624.

    Article  PubMed  CAS  Google Scholar 

  144. Weyman C, Graham-Pole J, Emerson S, et al. Use of cytosine arabinoside and total body irradiation as conditioning for allogeneic marrow transplantation in patients with acute lymphoblastic leukemia: a multicenter survey. Bone Marrow Transplant 1993; 11:43–50.

    PubMed  CAS  Google Scholar 

  145. Uderzo C, Rondelli R, Dini G, et al. High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study. Br J Haematol 1995;89:790–797.

    Article  PubMed  CAS  Google Scholar 

  146. Dopfer R, Henze G, Bender-Götze C, et al. Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study. Blood 1991;78:2780–2784.

    PubMed  CAS  Google Scholar 

  147. Moussalem M, Esperou Bourdeau H, Devergie A, et al. Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease. Bone Marrow Transplant 1995; 15:943–947.

    PubMed  CAS  Google Scholar 

  148. Barrett AJ, Horowitz MM, Pollock BH, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 1994;331:1253–1258.

    Article  PubMed  CAS  Google Scholar 

  149. Uderzo C, Valsecchi MG, Bacigalupo A, et al. Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association. J Clin Oncol 1995;13:352–358.

    PubMed  CAS  Google Scholar 

  150. Schroeder H, Gustafsson G, Saarinen-Pihkala UM, et al. Allogeneic bone marrow transplantation in second remission of childhood acute lymphoblastic leukemia: a population-based case control study from the Nordic countries. Bone Marrow Transplant 1999;23:555–560.

    Article  PubMed  CAS  Google Scholar 

  151. Borgmann A, Baumgarten E, Schmid H, et al. Allogeneic bone marrow transplantation for a subset of children with acute lymphoblastic leukemia in third remission: a conceivable alternative? Bone Marrow Transplant 1997;20:939–944.

    Article  PubMed  CAS  Google Scholar 

  152. Beatty PG, Hansen JA, Longton GM, et al. Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 1991;51:443–447.

    Article  PubMed  CAS  Google Scholar 

  153. Kernan NA, Bartsch G, Ash RC, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 1993;328:593–602.

    Article  PubMed  CAS  Google Scholar 

  154. Weisdorf DJ, Billett AL, Hannan P, et al. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood 1997;90:2962–2968.

    PubMed  CAS  Google Scholar 

  155. Oakhill A, Pamphilon DH, Potter MN, et al. Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission. Br J Haematol 1996;94:574–578.

    Article  PubMed  CAS  Google Scholar 

  156. Lausen BF, Heilmann C, Vindelov L, Jacobsen N. Outcome of acute lymphoblastic leukaemia in Danish children after allogeneic bone marrow transplantation. Superior survival following transplantation with matched unrelated donor grafts. Bone Marrow Transplant 1998;22:325–330.

    Article  PubMed  CAS  Google Scholar 

  157. Ringden O, Labopin M, Gluckman E, et al. Donor search or autografting in patients with acute leukaemia who lack an HLA-identical sibling? A matched-pair analysis. Acute Leukaemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation (EBMT) and the International Marrow Unrelated Search and Transplant (IMUST) Study. Bone Marrow Transplant 1997;19:963–968.

    Article  PubMed  CAS  Google Scholar 

  158. Knechtli CJ, Goulden NJ, Hancock JP, et al. Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia. Blood 1998;92: 4072–4079.

    PubMed  CAS  Google Scholar 

  159. Kersey JH, Weisdorf D, Nesbit ME, et al. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med 1987;317:461–467.

    Article  PubMed  CAS  Google Scholar 

  160. Billett AL, Kornmehl E, Tarbell NJ, et al. Autologous bone marrow transplantation after a long first remission for children with recurrent acute lymphoblastic leukemia. Blood 1993;81:1651–1657.

    PubMed  CAS  Google Scholar 

  161. Messina C, Cesaro S, Rondelli R, et al. Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in Italy. AIEOP/FONOP-TMO Group. Italian Association of Paediatric Haemato-Oncology. Bone Marrow Transplant 1998;21: 1015–1021.

    Article  PubMed  CAS  Google Scholar 

  162. Messina C, Valsecchi MG, Arico M, et al. Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/ FONOP-TMO Group. Associzione Italiana Emato-Oncologia Pediatrica. Bone Marrow Transplant 1998;21:9–14.

    Article  PubMed  CAS  Google Scholar 

  163. Borgmann A, Schmid H, Hartmann R, et al. Autologous bonemarrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matchedpair analysis. The Berlin-Frankfurt-Münster Study Group. Lancet 1995;346:873–876.

    Article  PubMed  CAS  Google Scholar 

  164. Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol 1997;15:1767–1777.

    PubMed  CAS  Google Scholar 

  165. Kawano Y, Takaue Y, Watanabe A, et al. Partially mismatched pediatric transplants with allogeneic CD34(+) blood cells from a related donor. Blood 1998;92:3123–3130.

    PubMed  CAS  Google Scholar 

  166. Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998;339: 1186–1193.

    Article  PubMed  CAS  Google Scholar 

  167. Locatelli F, Rocha V, Chastang C, et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93:3662–3671.

    PubMed  CAS  Google Scholar 

  168. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998;91:756–763.

    PubMed  CAS  Google Scholar 

  169. Borgmann A, von Stackelberg A, Baumgarten E, et al. Immunotherapy of acute lymphoblastic leukemia by vaccination with autologous leukemic cells transfected with a cDNA expression plasmid coding for an allogeneic HLA class I antigen combined with interleukin-2 treatment. J Mol Med 1998;76:215–221.

    Article  PubMed  CAS  Google Scholar 

  170. Stripecke R, Skelton DC, Pattengale PK, Shimada H, Kohn DB. Combination of CD80 and granulocyte-macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: preclinical studies in a murine model recapitulating Philadelphia chromosomepositive acute lymphoblastic leukemia. Hum Gene Ther 1999; 10:2109–2122.

    Article  PubMed  CAS  Google Scholar 

  171. Stripecke R, Skelton DC, Gruber T, et al. Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia induced by expression of CD80, interleukin 2, and granulocytemacrophage colony-stimulating factor. Hum Gene Ther 1998; 9:2049–2062.

    Article  PubMed  CAS  Google Scholar 

  172. Pinilla-Ibarz J, Cathcart K, Korontsvit T, et al. Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 2000;95:1781–1787.

    PubMed  CAS  Google Scholar 

  173. Matthews DC, Appelbaum FR, Eary JF, et al. Phase I study of (131)I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood 1999;94:1237–1247.

    PubMed  CAS  Google Scholar 

  174. Lawson SE, Harrison G, Richards S, et al. The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the Medical Research Council UKALLR1 study. Br J Haematol 2000;108:531–543.

    Article  PubMed  CAS  Google Scholar 

  175. Finklestein JZ, Miller DR, Feusner J, et al. Treatment of overt isolated testicular relapse in children on therapy for acute lymphoblastic leukemia. A report from the Children’s Cancer Group. Cancer 1994;73:219–223.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Günter Henze
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arend Von Stackelberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, Memphis, TN, USA

    Ching-Hon Pui MD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Henze, G., Von Stackelberg, A. (2003). Treatment of Relapsed Acute Lymphoblastic Leukemia. In: Pui, CH. (eds) Treatment of Acute Leukemias. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-307-1_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-307-1_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-212-4

  • Online ISBN: 978-1-59259-307-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation