European Journal of Pediatrics

, Volume 151, Supplement 1, pp S50–S54 | Cite as

Chemotherapy versus bone marrow transplantation in childhood acute lymphoblastic leukaemia

  • W. Ebell
  • A. Reiter
  • H. Riehm
  • on behalf of the BFM study group
Article

Abstract

Twenty-five years ago over 90% of children with acute lymphoblastic leukaemia (ALL) died of this disease. Dramatic improvement has been achieved since then by employing risk-adapted, aggressive polychemotherapy protocols. More than 90% of children with ALL treated according to, for example BFM-protocols, have nowadays cure rates in the range of 70%–80%. However, 10% of patients do not initially respond adequately to standard induction chemotherapy. They are characterized by distinct chromosomal abnormalities such as translocation (9; 22) or combinations of early treatment failure and other risk factors as cytogenetic abnormalities, lineage-specific surface markers or tumour load at diagnosis. In this group of patients in first complete remission and certainly in the vast majority of relapsed patients, allogeneic bone marrow transplantation (BMT) has evolved as an alternative approach allowing further intensification of myeloablation and the introduction of an additional antileukaemic alloreactivity. Nevertheless, the decision for a marrow transplant in children has to be made very carefully because of a significant increase in treatment related mortality and BMT-specific risks like acute and chronic graft-versus-host disease with a critical iatrogenic chronic morbidity. This is even more evident, if mismatched or unrelated transplants are being considered. The indications for one or the other treatment modality according to the current BFM strategy are discussed.

Key words

Acute lymphoblastic leukaemia Bone marrow transplantation Chemotherapy Risk factors 

Abbreviations

ALL

acute lmyphoblastic leukaemia

BFM

German/Austrian co-operative group for the treatment of childhood leukaemias, originally named after the founding centres in Berlin-Frankfurt-Münster

BMT

bone marrow transplantation

EFS

event free survival according to life table analysis (Kaplan-Mejer analysis)

GVHD

chronic graftversus-host disease

VP16

etoposide

References

  1. 1.
    Atkinson K, Horowitz MM, Gale RP, Bekkum DW van, Gluckman E, Good RA, Jacobsen N, Kolb HJ, Rimm AA, Ringden O, Rozman C, Sobocinski KA, Zwaan FE, Bortin MM (1990) Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 75:2459–2464PubMedGoogle Scholar
  2. 2.
    Baum E, Nachman J, Ramsay N, Weetman B, Neerhout R, Littman P, Griffin T, Norris D, Sather H (1983) Prolonged second remissions in childhood acute lymphocytic leukaemia: a report from the childrens cancer study group. Med Pediatr Oncol 11:1–7PubMedGoogle Scholar
  3. 3.
    Birch JM (1983) Epidemiology of paediatric cancer, In: Duncan W (ed) Paediatric Oncology. Springer, Berlin Heidelberg New York, pp 1–10Google Scholar
  4. 4.
    Blaise D, Gaspard MH, Stoppa AM, Michel G, Gastaut JA, Lepeu G, Tubiana N, Blanc AP, Rossi JF, Novakovitch G, Mannoni P, Mavas C, Maraninchi D, Carcassonne Y (1990) Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission. Bone Marrow Transplant 5:7–12PubMedGoogle Scholar
  5. 5.
    Bleyer WA (1990) Acute lymphoblastic leukemia in children. Cancer 65:689–695PubMedGoogle Scholar
  6. 6.
    Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ (1987) Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 317:1618PubMedGoogle Scholar
  7. 7.
    Burchenal JH, Murphy ML (1965) Long-term survivors in acute leukaemia. Cancer Res 25:1491–1494PubMedGoogle Scholar
  8. 8.
    Colleselli P, Dini G, Andolina M, Bonetti F, Miniero R, Sonego M, Pigozzo P, Messina C, Forta F, Sotti G, Zanesco L (1991) Autologous bone marrow transplantation for acute lymphoblastic leukemia: the high dose vincristine study of AIEOP BMT group. Bone Marrow Transplatn 7 [Suppl 3]:28–30Google Scholar
  9. 9.
    Crist WM, Shuster JJ, Falletta J, Pullen DJ, Berard WC, Vietti TJ, Alvarado CS, Roper MA, Prasthofer E, Crossi CE (1988) Clinical features and outcome in childhood T-cell leukaemia-lymphoma according to stage of thymocyte differentiation. A Pediatric Oncology Group Study. Blood 72:1891Google Scholar
  10. 10.
    Crist W, Carroll A, Shuster J, Kackson J, Head D, Borowitz M, Behm F, Link M, Steuber P, Ragab A, Hirt A, Brock B, Land V, Pullen J (1990) Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study. Blood 76:489–494Google Scholar
  11. 11.
    Deeg HJ, Henslee-Downey PJ (1990) Management of acute graft-versus-host disease. Bone Marrow Transplant 6:1–8Google Scholar
  12. 12.
    Dopfer R, Henze G, Bender-Götze C, Ebell W, Ehninger G, Friedrich W, Gadner H, Klingebiel T, Peters C, Riehm H, Suttorp M, Schmid H, Schmitz N, Siegert W, Stollmann-Gibbels B, Hartmann R, Niethammer D (1991) 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 78:2780–2784PubMedGoogle Scholar
  13. 13.
    Forman SJ, O'Donnell MR, Nademanee AP, Snyder DS, Bierman PJ, Schmidt GM, Fahey JL, Stein AS, Parker PM, Blume KG (1987) Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 70:587–588PubMedGoogle Scholar
  14. 14.
    Freeman AI, Weinberg V, Brecher ML, Jones B, Glicksman AS, Sinks LF, Weil M, Pleuss H, Hananian J, Burgert EO, Gilchrist GS, Necheless T, Harris M, Kung F, Patterson RB, Maurer H, Leventhal B, Chevalier L, Forman E, Holland JF (1983) Comparison of intermediate-dose methotrexate with cranial irradiation for the postinduction treatment of acute lymphocytic leukaemia in children. N Engl Med 308:477–484Google Scholar
  15. 15.
    Gasser C (1980) Long-term survival (cures) in childhood acute leukaemia. Paediatrician 9:344–357PubMedGoogle Scholar
  16. 16.
    Gaynon PS, Steinherz PS, Bleyer WA, et al (1988) Intensive therapy for children with acute lymphoblastic leukaemia and unfavourable presenting features. Lancet II:921–924CrossRefGoogle Scholar
  17. 17.
    Goldstone AH, Souhami RL, Linch DC, Anderson CC, Harper PG, Machin S, Jellife (1984) Intensive Chemotherapy and autologous bone marrow transplantation for relapsed lymphoma. Exp Hematol 12:137Google Scholar
  18. 18.
    Gratwohl A, Hermans J, Barrett AJ, Ernst P, Frassoni F, Gahrton G, Granena A, Kolb HJ, Prentice HG, Vernant JP, Zwaan FE (1990) Allogeneic bone marrow transplantation for leukaemia in Europe: regional differences. Report from the leukaemia working party of the European Group for Bone marrow Transplantation. Bone Marrow Transplant 5:159–165PubMedGoogle Scholar
  19. 19.
    Gray R, Wheatley K, MRC Clinical Trial Service Unit (1991) How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant 7 [Suppl 3]: 9–12Google Scholar
  20. 20.
    Henze G, Fengler R, Hartmann R, Kornhuber B, Janka-Schaub G, Niethammer D, Riehm H (1991) 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 78:1166–1172Google Scholar
  21. 21.
    Howard MR (1990) Strategies for selection of unrelate marrow donors. New Trends Ther Leuk Lymph 5:3–8Google Scholar
  22. 22.
    Howard MR, Hows JM, Gore SM, Bradley BA (1991) Unrelated donor marrow transplantation: an interim analysis of the International marrow unrelated search and transplant (IMUST) study II. Bone Marrow Transplant 7 [Suppl 2]:126PubMedGoogle Scholar
  23. 23.
    Ludwig WD, Seibt-Jung H, Teichmann JV, Komischke B, Gatzke A, Gassner G, Odenwald E, Hofmann J, Riehm H (1989) Clinicopathological features and prognostic implications of immunephenotypic subgroups in childhood ALL: experience of the BFM-ALL Study 83. In: Neth RD, et al (eds) Modern trends in human leukemia VIII. Springer, Berlin Heidelberg New York, pp 51–57Google Scholar
  24. 24.
    Ludwig WD, Thiel E, Löller U, Bartram CR, Harbott J, Teichmann JV, Seibt-Jung H, Creutzig U, Ritter J, Riehm H (1989) Incidence and clinical implications of acute hybrid leukemia in childhood. Hamatol Bluttransfus 33:516–522Google Scholar
  25. 25.
    Nesbit ME, Sather HN, Robinson LL, Ortega JA, Hammond GD, Children's Cancer Study Group (1983) Randomized study of 3 years versus 5 years of chemotherapy in childhood acute lymphoblastic leukaemia. J Clin Oncol 1:308–316PubMedGoogle Scholar
  26. 26.
    Niethammer D, Klingebiel T, Riehm H, Henze G, Schellong G, Bender-Götze C, Dopfer R, Ebell W, Friedrich W, Haas RJ, Schmitz N, Stollmann B (1991) Role and perspectives of BMT in ALL: the BFM experience. Bone Marrow Transplant 7 [Suppl 3]:14–18PubMedGoogle Scholar
  27. 27.
    Paolucci P, Dini G, Dallorso S, Meloni G, Locasciulli A, Andolina M, De Manzini A, Schettini F, Pession A (1991) Bone marrow transplantation in childhood: a report from the AIEOP-BMT group registry. Bone Marrow Transplant 7 [Suppl 3]:3–8PubMedGoogle Scholar
  28. 28.
    Philip T, Hartmann O, Biron P, Chan JY, Pein F, Bordigoni P, Souillet G, Gartner M, Lasset C, Chauvin F (1988) Highdose therapy and autologous bone marrow transplantation in partial remission after first-line induction therapy for diffuse non-Hodgkin's lymphoma. J Clin Oncol 6:1118–1124PubMedGoogle Scholar
  29. 29.
    Pui CH, Behm FG, Singh B, Rivera GK, Schell MJ, Roberts WM, Crist WM, Mirro J (1990) Myeloid-associated antigen expression lacks prognostic value in childhood acute lymphoblastic leukemia treated with intensive multiagent chemotherapy. Blood 75:198–202PubMedGoogle Scholar
  30. 30.
    Pui CH, Carroll AJ, Raimondi SC, Land VJ, Crist WM, Shuster JJ, Williams DL, Pullen DJ, Borowitz MJ, Behm FG, Look AT (1990) Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid <45 line. Blood 75:1170–1177PubMedGoogle Scholar
  31. 31.
    Pui CH, Crist WM, Look T (1990) Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia. Blood 76:1449–1463PubMedGoogle Scholar
  32. 32.
    Ramsay NKC, Kersey JH (1990) Indications for marrow transplantation in acute lymphoblastic leukaemia. Blood 75:815–818PubMedGoogle Scholar
  33. 33.
    Reiter A, Schrappe M, Ludwig WD, Lampert F, Harbott J, Henze G, Niemeyer CM, Gadner H, Müller-Weihrich S, Ritter J, Odenwald E, Riehm H (1992) Favorable outcome of B-cell acute lymphoblastic leukemia (B-ALL) in childhood. A report of three consecutive studies of the BFM group. Blood (in press)Google Scholar
  34. 34.
    Riehm H, Gadner H, Henze G, Kornhuber B, Lampert F, Niethammer D, Reiter A, Schellong G (1990) Results and significance of six randomized trials in four consecutive ALL-BFM studies. Hamatol Bluttransfus 33:439–450Google Scholar
  35. 35.
    Sallan SE, Niemeyer CM, Billet AL, Lipton JM, Tarbel NJ, Gelber RD, Murray C, Pittinger TP, Wolfe LC, Bast RC, Ritz J (1989) Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 7:1594–1601PubMedGoogle Scholar
  36. 36.
    Slavin S, Ackerstein A, Naparstek E, Or R, Weiss L (1990) The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? Bone Marrow Transplant 6:155–161PubMedGoogle Scholar
  37. 37.
    Thomas ED (1983) Bone marrow transplantation in malignant diseases. J Clin Oncol 1:517–531PubMedGoogle Scholar
  38. 38.
    Thomas ED, Buckner CD, Rudolph RH, Fefer A, Storb R, Neiman PE, Bryant JI, Chard RL, Clift RA, Epstein RB, Fialkow PJ, Funk DD, Giblett ER, Lerner KG, Reynolds FA, Slichter S (1971) Allogeneic marrow grafting for hematologic malignancy using HLA matched donor-recipient sibling pairs. Blood 38:276–287Google Scholar
  39. 39.
    Uckun KM, Kersey JH, Haake R, Weisdorf D, Ramsay KC (1992) Autologous bone marrow transplantation in high-risk remission B-lineage acute lymphoblastic leukemia using a cocktail of three monoclonal antibodies (BA-1/CD24, BA-2/CD9, and BA-3/CD10) plus complement and 4-hydroperoxycyclophosphamide for ex vivo bone marrow purging. Blood 79:1094–1104PubMedGoogle Scholar
  40. 40.
    Uderzo C, Coleselli P, Messina C, Dini G, Bonetti F, Andolina M, Bagnulo S, Miniero R, Rondelli R, Paoulucce P, Balduzzi A, Bonomi M, Locasciulli A (1991) Allogeneic BMT versus autologous BMT in childhood acute lymphoblastic leukemia (ALL): an Italian cooperative study of vincristine (VCR), F-TBI and cyclophosphamide. Bone Marrow Transplant 7 [Suppl 2]:132PubMedGoogle Scholar
  41. 41.
    Weisdorf DJ, McGlave PB, Ramsay NKC, Miller WJ, Nesbit ME, Woods WG, Goldman AI, Kim TH, Kersey JH (1988) Allogeneic bone marrow transplantation for acute leukaemia: comparative outcomes for adults and children. Br J Haematol 69:351–358PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • W. Ebell
    • 1
  • A. Reiter
    • 1
  • H. Riehm
    • 1
  • on behalf of the BFM study group
  1. 1.Department of Paediatric Hematology and OncologyChildren's Hospital, Hannover Medical SchoolHannover 61Germany

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