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Relapsed acute lymphoblastic leukemia: Current status and future opportunities

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Abstract

Significant improvements in primary therapy for childhood acute lymphoblastic leukemia (ALL) have led to dramatic increases in cure rates over the past few decades. Relapsed ALL, however, remains more common than new diagnoses of many common pediatric malignancies. Outcomes for patients with relapsed ALL remain poor, especially for patients with early bone marrow relapse. However, most relapse patients do achieve a second complete remission, followed by therapeutic options including further chemotherapy and hematopoietic stem cell transplant. The level of minimal residual disease after achieving second remission or before transplant may predict outcomes. The substantial likelihood of achieving second remission with familiar drug combinations may discourage participation in formal relapse studies. The high likelihood of achieving a third remission may discourage participation in single-gent trials of new drugs, despite the critical need for novel agents with activity against resistant disease that may improve outcomes for recurrent ALL.

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References and Rcommended Rading

  1. Grovas A, Fremgen A, Rauck A, et al.: The National Cancer Data Base report on patterns of childhood cancers in the United States. Cancer 1997, 80:2321–2332.

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Tiwari RC, Murray T, et al.: Cancer statistics, 2004. CA Cancer J Clin 2004, 54:8–29.

    Article  PubMed  Google Scholar 

  3. Pui CH, Evans WE: Treatment of acute lymphoblastic leukemia. New Engl J Med 2006, 354:166–178.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Nguyen K, Cheng SC, Raetz E, et al.: Factors influencing survival after relapse from childhood ALL: a Children’s Oncology Group Study [abstract]. Blood 2006, 108:1855.

    Google Scholar 

  6. Eapen M, Raetz E, Zhang MJ, et al.: Outcomes after HLA-atched 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  PubMed  CAS  Google Scholar 

  7. Gaynon PS, Harris RE, Altman AJ, et al.: Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children’s Oncology Group study CCG-1941. J Clin Oncol 2006, 24:3150–3156.

    Article  PubMed  Google Scholar 

  8. Chessells JM, Veys P, Kempski H, et al.: Long-term followup of relapsed childhood acute lymphoblastic leukaemia. Br J Haematol 2003, 123:396–405.

    Article  PubMed  Google Scholar 

  9. Eckert, C, Biondi, A, Seeger, K, et al.: Prognostic value of minimal residual disease in relapsed childhood acute lymphoblastic leukaemia. Lancet 2001, 358:1239–1241.

    Article  PubMed  CAS  Google Scholar 

  10. Coustan-Smith E, Gajjar A, Hijiya N, et al.: Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. Leukemia 2004, 18:499–504.

    Article  PubMed  CAS  Google Scholar 

  11. Bader P, Hancock J, Kreyenberg H, et al.: Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL. Leukemia 2002, 16:1668–1672.

    Article  PubMed  CAS  Google Scholar 

  12. Goulden N, Bader P, van der Velden V, et al.: Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia. Br J Haematol 2003, 122:24–29.

    Article  PubMed  Google Scholar 

  13. 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 

  14. Gaynon PS: Childhood acute lymphoblastic leukaemia and relapse. Br J Haematol 2005, 131:579–587.

    Article  PubMed  Google Scholar 

  15. Raetz EA, Borowitz MJ, Devidas M, et al.: Outcomes of children with first marrow relapse: results from Children’s Oncology Group (COG) Study AALL01P2 [abstract]. Blood 2006, 108:1871.

    Google Scholar 

  16. 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 

  17. Roy, A, Cargill A, Love S, et al.: Outcome after first relapse in childhood acute lymphoblastic leukaemia-lessons from the United Kingdom R2 trial. Br J Haematol 2005, 130:67–75.

    Article  PubMed  Google Scholar 

  18. Einsiedel HG, von Stackleberg A, Hartmann R, et al.: Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt Munster Group 87. J Clin Oncol 2005, 23:7942–7950.

    Article  PubMed  Google Scholar 

  19. Ko R, Ji L, Sposto R, et al.: Retrospective analysis of children treated for relapsed and refractory leukemia-a report from the Therapeutic Advances in Childhood Leukemia Consortium (TACL) [abstract]. ASH Annual Meeting Abstracts 2007, 110:854.

    Google Scholar 

  20. Malempati S, Gaynon PS, Sather H, et al.: Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children’s Oncology Group Study CCG-1952. J Clin Oncol 2007, 25:5800–5807.

    Article  PubMed  Google Scholar 

  21. Mehta PA, Davies SM: Allogeneic transplantation for childhood ALL. Bone Marrow Transplant 2008, 41:133–139.

    Article  PubMed  CAS  Google Scholar 

  22. Marks DI, Forman SJ, Blume KG, 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, 12:438–453.

    Article  PubMed  CAS  Google Scholar 

  23. Eapen M, Zhang MJ, Devidas M, et al.: Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated CNS relapse: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia 2008, 22:281–286.

    Article  PubMed  CAS  Google Scholar 

  24. Pui CH, Jeha S: Clofarabine. Nat Rev Drug Discov 2005, 4:369–370.

    Article  PubMed  CAS  Google Scholar 

  25. Kurtzberg J: The long and winding road of the clinical development of nelarabine. Leuk Lymphoma 2007, 48:1–2.

    Article  PubMed  CAS  Google Scholar 

  26. Jeha S, Gaynon PS, Razzouk BI, et al.: Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood 2004, 103:784–789.

    Article  PubMed  CAS  Google Scholar 

  27. Jeha S, Rassouk BI, Gaynon P, et al.: Clofarabine in children with refractory/relapsed acute leukemia: results of 2 phase II open label studies [abstract]. ASH Annual Meeting Abstracts 2006, 108:4460.

    Google Scholar 

  28. Hijaya N, Franklin J, Rytting M, et al.: A phase I study of clofarabine in combination with cyclophosphamide and etoposide: a new regimen in pediatric patients with relapsed or refractory acute leukemia. Proc Am Soc Clin Oncol 2007, 26:9529.

    Google Scholar 

  29. Cooper T, Ayres M, Nowak B, et al.: Biochemical modulation of cytarabine triphosphate by clofarabine. Cancer Chemother Pharmacol 2005, 55:361–368.

    Article  PubMed  CAS  Google Scholar 

  30. Faderl S, Gandhi V, O’Brien S, et al.: Results of a phase 1–2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood 2005, 105:940–947.

    Article  PubMed  CAS  Google Scholar 

  31. Kisor D: Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias. Ann Pharmacother 2005, 39:1056–1063.

    Article  PubMed  CAS  Google Scholar 

  32. Berg, SL BS, Devidas M, Lampkin TA, et al.: Phase II study of nelarabine (compound 506U78) in children and young adults with refractory t-cell malignancies: a report from the Children’s Oncology Group. J Clin Oncol 2005, 23:3376–3382.

    Article  PubMed  CAS  Google Scholar 

  33. Carnahan J, Stein R, Qu Z, et al.: Epratuzumab, a CD22-targeting recombinant monoclonal humanized antibody with a different mode of action from rituximab. Mol Immunol 2007, 44:1331–1341.

    Article  PubMed  CAS  Google Scholar 

  34. Goldenberg DM: Epratuzumab in the therapy of oncological and immunological diseases. Expert Rev Anticancer Ther 2006, 6:1341–1353.

    Article  PubMed  CAS  Google Scholar 

  35. Micallef IN, Kahl BS, Maurer MJ, et al.: A pilot study of eprazumab and rituxan in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy in patients with previously untreated, diffuse large B-cell lymphoma. Cancer 2006, 107:2826–2832.

    Article  PubMed  CAS  Google Scholar 

  36. Horton TM, Gannavarapu A, Blaney SM, et al.: Bortezomib interactions with chemotherapy agents in acute leukemia in vitro. Cancer Chemother Pharmacol 2006, 58:13–23.

    Article  PubMed  CAS  Google Scholar 

  37. Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997, 3:917–921.

    Article  PubMed  CAS  Google Scholar 

  38. Troeger A, Siepermann M, Escherich G, et al.: Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. Haematologica 2007, 92:1043–1050.

    Article  PubMed  CAS  Google Scholar 

  39. Kang MH, Kang YH, Szymanska B, et al.: Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood 2007, 110:2057–2066.

    Article  PubMed  CAS  Google Scholar 

  40. Crooks GM, Sato JK: Ifosfamide and etoposide in recurrent childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 1995, 17:34–38.

    Article  PubMed  CAS  Google Scholar 

  41. Harris RE, Sather HN, Feig SA: High dose cytosine arabinoside and L-asparaginase in refractory acute lymphoblastic leukemia: the Children’s Cancer Group experience. Med Pediatr Oncol 1998, 30:233–239.

    Article  PubMed  CAS  Google Scholar 

  42. Bernstein ML, Abshire TC, Pollock BH, et al.: Idarubicin and cytosine arabinoside reinduction therapy for children with multiple recurrent or refractory acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 1997, 19:68–72.

    Article  PubMed  CAS  Google Scholar 

  43. Kurtzberg J, Asselin B, Pollock B, et al.: PEG L-asparaginase (PEGasp) vs native E. coli asparaginase (asp) for reinduction of relapsed acute lymphoblastic leukemia (ALL): Pediatric Oncology Group (POG) 8866 Phase II trial. Proc Am Soc Clin Oncol 1993, 12:325.

    Google Scholar 

  44. Kolb EA, Steinherz PG: A multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute lymphoblastic leukemia. Leukemia 2003, 17:1967–1972.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Theresa M. Harned.

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Harned, T.M., Gaynon, P.S. Relapsed acute lymphoblastic leukemia: Current status and future opportunities. Curr Oncol Rep 10, 453–458 (2008). https://doi.org/10.1007/s11912-008-0070-3

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