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Allogeneic transplantation for childhood ALL

Bone Marrow Transplantation volume 41, pages 133–139 (2008)Cite this article

Abstract

More than 80% of children with ALL are now cured with chemotherapy without need for transplantation. This remarkable progress is the result of serial large-scale randomized clinical trials incorporating improvements in risk group assignment, administration of risk-adjusted therapy and intensified therapy for children with high-risk disease. Despite these advances, significant numbers of children still die of relapsed or refractory ALL, as ALL is the most frequent malignancy of childhood. This review focuses on the appropriate use of transplantation for children with ALL and optimization of transplant procedures to improve survival and reduce late consequences of therapy.

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References

  1. Schultz KR, Pullen DJ, Sather HN, Shuster JJ, Devidas M, Borowitz MJ et al. Risk-and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG). Blood 2007; 109: 926–935.

    Article  CAS  Google Scholar 

  2. Aricò M, Valsecchi MG, Camitta B, Schrappe M, Chessell 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.

    Article  Google Scholar 

  3. Marks DI, Bird JM, Cornish JM, Goulden NJ, Jones CG, Knechtli CJ et al. Unrelated donor bone marrow transplantation for children and adolescents with Philadelphia-positive acute lymphoblastic leukemia. J Clin Oncol 1998; 16: 931–936.

    Article  CAS  Google Scholar 

  4. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J et al. Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1997; 90: 1410–1414.

    CAS  PubMed  Google Scholar 

  5. Roy A, Bradburn M, Moorman AV, Burrett J, Love S, Kinsey SE et al. Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial. Br J Haematol 2005; 129: 35–44.

    Article  Google Scholar 

  6. Talano JM, Casper JT, Camitta BM, Keever-Taylor CA, Murray KJ, Eapen M et al. Alternative donor bone marrow transplant for children with Philadelphia chromosome ALL. Bone Marrow Transplant 2006; 37: 135–141.

    Article  CAS  Google Scholar 

  7. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavo A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  Google Scholar 

  8. Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2006; 108: 1469–1477.

    Article  CAS  Google Scholar 

  9. Carpenter PA, Snyder DS, Flowers ME, Sanders JE, Gooley Ta, Martin PJ et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood 2007; 109: 2791–2793.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 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 Children's Cancer Group. Blood 1999; 94: 4036–4046.

    CAS  PubMed  Google Scholar 

  11. 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: 1112–1115.

    Article  CAS  Google Scholar 

  12. Conter V, Aricò M, Valsecchi MG, Basso G, Biondi A, Madon E et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Acute Lymphoblastic Leukemia Studies, 1982–1995. Leukemia 2000; 14: 2196–2204.

    Article  CAS  Google Scholar 

  13. Satwani P, Sather H, Ozkaynak F, Heerema NA, Schultz KR, Sanders J et al. Allogenic bone marrow transplantation in first remission for children with ultra-high-risk features of acute lymphoblastic leukemia: a children's oncology group study report. Biol Blood Marrow Transplant 2007; 13: 218–227.

    Article  CAS  Google Scholar 

  14. Bordigoni P, Vernant JP, Souillet G, Gluckman E, Marininchi D, Milpied N et al. Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la greffe de Moelle Osseuse. J Clin Oncol 1989; 7: 747–753.

    Article  CAS  Google Scholar 

  15. Chao NJ, Forman SJ, Schmidt GM, Snyder DS, Amylon MD, Konrad PN et al. Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission. Blood 1991; 78: 1923–1927.

    CAS  PubMed  Google Scholar 

  16. Borgmann A, Baumgarten E, Schmid H, Dopfer R, Ebell W, Gobel U 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  CAS  Google Scholar 

  17. Afify Z, Hunt L, Green A, Guttridge M, Cornish J, Oakhill A et al. Factors affecting the outcome of stem cell transplantation from unrelated donors for childhood acute lymphoblastic leukemia in third remission. Bone Marrow Transplant 2005; 35: 1041–1047.

    Article  CAS  Google Scholar 

  18. Borowitz MJ, Pullen DJ, Shuster JJ, Viswanatha D, Montgomery K, William CL et al. Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study. Leukemia 2003; 17: 1566–1572.

    Article  CAS  Google Scholar 

  19. Nyvold C, Madsen HO, Ryder LP, Seyfarth J, Svejgaad A, Clausen N et al. Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and excellent outcome. Blood 2002; 99: 1253–1258.

    Article  CAS  Google Scholar 

  20. Dworzak MN, Froschi G, Printz D, Mann G, Potschger U, Muhlegger N et al. Prognostic significance and modalities of flow cytometric minimal residual detection in childhood acute lymphoblastic leukemia. Blood 2002; 15: 1952–1958.

    Article  Google Scholar 

  21. Tarusawa M, Yashima A, Endo M, Maesawa C . Quantitative assessment of minimal residual disease in childhood lymphoid malignancies using an allele-specific oligonucleotide real-time quantitative polymerase chain reaction. Int J Hematol 2002; 75: 166–173.

    Article  CAS  Google Scholar 

  22. Willlemse MJ, Seriu T, Hetteringer K, d'Aniello E, Hop WC, Panzer-Grumayer ER et al. Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL. Blood 2002; 15: 4386–4393.

    Article  Google Scholar 

  23. Coustan-Smith E, Sancho J, Behm FG, Hancock ML, Razzouk BI, Ribeiro RC et al. Prognostic importance of measuring early clearance of leukemia cell by flow cytometry in childhood acute lymphoblastic leukemia. Blood 2002; 100: 52–58.

    Article  CAS  Google Scholar 

  24. Ross ME, Zhou X, Song G, Shurleff SA, Girtman K, Williams WK et al. Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 2003; 102: 2951–2959.

    Article  CAS  Google Scholar 

  25. Haferlach T, Kohlmann A, Schnittger S, Dugas M, Hiddemann W, Kern W et al. Global approach to the diagnosis of leukemia using gene expression profiling. Blood 2005; 106: 1189–1198.

    Article  CAS  Google Scholar 

  26. Hollerman A, Cheok MH, den Boer ML, Yang W, Veerman AJ, Kazemier KM et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med 2004; 351: 601–603.

    Article  Google Scholar 

  27. Flotho C, Coustan-Smith E, Pei D, Cheng C, Song G, Pui CH et al. A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia. Blood 2007; 110: 1271–1277.

    Article  CAS  Google Scholar 

  28. Uzunel M, Jaksch M, Mattsson J, Ringden O . Minimal residual disease detection after allogeneic stem cell transplantation is correlated to relapse in patients with acute lymphoblastic leukemia. Br J Haematol 2003; 122: 788–794.

    Article  Google Scholar 

  29. Schilham MW, Balduzzi A, Bader P . PD-WP of the EBMT. Bone Marrow Transplant 2005; 1: 49–52.

    Article  Google Scholar 

  30. Sramkova L, Muzikova K, Fronkova E, Krejci O, Sedlacek P, Formankova R et al. Detectable minimal residual disease before allogeneic hematopoietic stem cell transplantation predicts extremely poor prognosis in children with acute lymphoblastic leukemia. Pediatric Blood Cancer 2007; 48: 93–100.

    Article  Google Scholar 

  31. Chen CS, Sorensen HB, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA et al. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variable and poor outcome. Blood 1993; 81: 2386–2393.

    CAS  PubMed  Google Scholar 

  32. Pui CH, Behm FG, Downing JR, Hancock ML, Shurleff SA, Riberiro RC et al. 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. J Clin Oncol 1994; 12: 909–915.

    Article  CAS  Google Scholar 

  33. Pui C-H, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet 2002; 359: 1909–1915.

    Article  Google Scholar 

  34. Sanders JE, IM HJ, Hoffmeister PA, Gooley TA, Woolfrey AE, Carpenter PA et al. Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia. Blood 2005; 105: 3749–3756.

    Article  CAS  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. Uderzo C, Valsecchi MG, Bacigalupo A, Meloni G, Messina C, Polchi P et al. Treatment of childhood acute lymphoblastic leukemia in second remission with 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; 134: 352–358.

    Article  Google Scholar 

  38. Dopfer R, Henze G, Bender-Gotze C, Ebell W, Ethniger G, Friedrich W 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.

    CAS  PubMed  Google Scholar 

  39. Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 340–347.

    Article  CAS  Google Scholar 

  40. Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S et al. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 2003; 32: 543–548.

    Article  CAS  Google Scholar 

  41. Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant 2006, 438–453.

    Article  CAS  Google Scholar 

  42. Barker JN, Krepski TP, DeFor TLE, Davies SM, Wagner JE, Weisdorf DJ et al. Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002; 8: 257–260.

    Article  Google Scholar 

  43. Bordigoni P, Vernant JP, Souillet G, Gluckman E, Marinichi D, Milpied N et al. Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe D'Etude de la Greffe de Moelle Osseuse. J Clin Oncol 1989; 7: 747–753.

    Article  CAS  Google Scholar 

  44. Von Bueltzingslowen A, Esperou-Bourdea H, Souillet G, Demeocq F, Mechinaud-Lacroix F, Michel G et al. Allogeneic bone marrow transplantation following a busulfan based conditioning regimen in young children with acute lymphoblastic leukemia: a Cooperative Study of the Societe Francaise de Greffe de Moelle. Bone Marrow Transplant 1995; 16: 521–527.

    Google Scholar 

  45. Saarinen UM, Mellander L, Nysom K, Ringden O, Schroeder H, Glomstein A et al. Allogeneic bone marrow transplantation in first remission for children with very high-risk acute lymphoblastic leukemia: a retrospective case–control study in the Nordic countries. Nordic society for Pediatric Hematology and Oncology (NOPHO). Bone Marrow Transplant 1996; 17: 357–363.

    CAS  PubMed  Google Scholar 

  46. Chessells JM, Baily C, Wheeler K, Richards SM . Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in first remission: experience in MRC UKALL X. Lancet 1992; 340: 565–568.

    Article  CAS  Google Scholar 

  47. Balduzzi A, Valsecchi M, 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.

    Article  Google Scholar 

  48. Ribera J, Ortega J, Oriol A, Bastida P, Calvo C, Pérez-Hurtado J et al. Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as post remission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial. J Clin Oncol 2007; 25: 16–24.

    Article  CAS  Google Scholar 

  49. Sanders JE, Thomas ED, Buckner CD, Doney K . Marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood 1987; 70: 324–326.

    CAS  PubMed  Google Scholar 

  50. Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D et al. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 1987; 317: 618–624.

    Article  Google Scholar 

  51. Woods WG, Nesbit ME, Ramsay NK, Krivit W, Kim TH, Goldman A et al. Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factor (a report from the University of Minnesota Bone Marrow Transplantation Team). Blood 1983; 6: 1182–1189.

    Google Scholar 

  52. Weisdorf DJ, Woods WG, Nesbit ME JR, Uckun F, Dusenbery K, Haake R et al. Allogeneic bone marrow transplantation for acute lymphoblastic leukemia: risk factors and clinical outcomes. Br J Haematol 1994; 86: 62–69.

    Article  CAS  Google Scholar 

  53. Parson SK, Casellino SM, Lehmann LE, Eickhoff CE, Tarbell NJ, Sallan SE et al. Relapsed acute lymphoblastic leukemia: similar outcomes for autologous and allogeneic marrow transplantation in selected children. Bone Marrow Transplant 1996; 17: 763–768.

    Google Scholar 

  54. Carpenter PA, Marshall GM, Giri N, Vowels MR, Russell SJ . Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia condition with busulfan, cyclophosphamide and melphalan. Bone Marrow Transplant 1996; 18: 489–494.

    CAS  PubMed  Google Scholar 

  55. Boulad F, Steinherz P, Reyes B, Heller G, Gillio P, Small TN et al. Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: a single-institution study. J Clin Oncol 1999; 17: 197–207.

    Article  CAS  Google Scholar 

  56. Bleakley M, Shaw PJ, Nielsen JM . Allogeneic bone marrow transplantation for childhood relapsed acute lymphoblastic leukemia: comparison of outcome in patients with and without a matched family donor. Bone Marrow Transplant 2002; 30: 1–7.

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  58. Green A, Clarke E, Hunt L, Canterbury A, Lankester A, Hale G et al. Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome. Blood 1999; 94: 2236–2246.

    CAS  PubMed  Google Scholar 

  59. Woolfrey AE, Anasetti C, Storer B, Doney K, Milner LA, Sievers EL et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood 2002; 99: 2002–2008.

    Article  CAS  Google Scholar 

  60. Bunin N, Carston M, Wall D, Adams R, Casper J, Kamani N et al. Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood 2002; 99: 3151–3157.

    Article  CAS  Google Scholar 

  61. 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.

    Article  CAS  Google Scholar 

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  1. Division of Hematology/Oncology, Department of Pediatrics, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    P A Mehta & S M Davies

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Mehta, P., Davies, S. Allogeneic transplantation for childhood ALL. Bone Marrow Transplant 41, 133–139 (2008). https://doi.org/10.1038/sj.bmt.1705914

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