Advertisement

Relapsed Pediatric ALL

  • Ayumu Arakawa
Chapter

Abstract

Although the survival of children with acute lymphoblastic leukemia has considerably improved in the previous two decades, 15–20% of patients experience subsequent relapse. Immunophenotype, duration of first complete remission, and site of relapse are the most widely accepted risk factors used for patient stratification in pediatric relapsed ALL. Patients with bone marrow (BM) relapse of T-ALL or very early or early BM relapse of BCP-ALL receive multi-drug chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with late BM relapse of BCP-ALL and negative minimal residual disease after re-induction undergo about 2 years of chemotherapy and can be treated without HSCT. Patients with late BM relapse of BCP-ALL who have poor minimal residual disease (MRD) response after re-induction are scheduled to receive HSCT at the time of second remission. Many novel agents for pediatric relapsed ALL have been developed in the previous decades.

Keywords

Pediatric relapsed acute lymphoblastic leukemia Risk classification Minimal residual disease Hematological stem cell transplantation Immunotherapy Molecular targeted drug Anti-CD19 chimeric-antigen receptor T-cell 

References

  1. 1.
    Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354(2):166–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Tsuchida M, Ohara A, Manabe A, Kumagai M, Shimada H, Kikuchi A, et al. Long-term results of Tokyo Children's cancer study group trials for childhood acute lymphoblastic leukemia, 1984–1999. Leukemia. 2010;24(2):383.PubMedCrossRefGoogle Scholar
  3. 3.
    Schrappe M, Bleckmann K, Zimmermann M, Biondi A, Möricke A, Locatelli F, et al. Reduced-intensity delayed intensification in standard-risk pediatric acute lymphoblastic leukemia defined by undetectable minimal residual disease: results of an international randomized trial (AIEOP-BFM ALL 2000). J Clin Oncol. 2018;36(3):244–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28(14):2339–47.PubMedCrossRefGoogle Scholar
  5. 5.
    Gaynon PS, Harris RE, Altman AJ, Bostrom BC, Breneman JC, Hawks R, 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(19):3150–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010;376(9757):2009–17.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's oncology group study. Leukemia. 2008;22(12):2142–50.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Weston BW, Hayden MA, Roberts KG, Bowyer S, Hsu J, Fedoriw G, et al. Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol. 2013;31(25):e413–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Bailey CL, Lange BJ, Rheingold SR, Bunin NJ. Bone-marrow relapse in paediatric acute lymphoblastic leukaemia. Lancet Oncol. 2008;9(9):873–83.PubMedCrossRefGoogle Scholar
  10. 10.
    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- 331(the Children's cancer group experience). Cancer. 1998;82(7):1387–95.PubMedCrossRefGoogle Scholar
  11. 11.
    Barrett AJ, Horowitz MM, Pollock BH, Zang MJ, Bortin MM, Buchanan GR, Camitta BM, 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(19):1253–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Lawson SE, Harrison G, Richards S, Oakhill A, Stevens R, Eden OG, 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(3):531–43.PubMedCrossRefGoogle Scholar
  13. 13.
    Einsiedel H, von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, 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-Münster group 87. J Clin Oncol. 2005;23(31):7942–50.PubMedCrossRefGoogle Scholar
  14. 14.
    von Stackelberg A, Hartmann R, Bührer C, Fengler R, Janka-Schaub G, Reiter A, et al. High-dose compared with intermediate-dose methotrexate in children with a first relapse of acute lymphoblastic leukemia. Blood. 2008;111(5):2573–80.CrossRefGoogle Scholar
  15. 15.
    Gaynon PS. Childhood acute lymphoblastic leukaemia and relapse. Br J Haematol. 2005;131(5):579–87.PubMedCrossRefGoogle Scholar
  16. 16.
    Bhojwani D, Pui C-H. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14(6):e205–17.PubMedCrossRefGoogle Scholar
  17. 17.
    Locatelli F, Schrappe M, Bernardo M, Rutella S. How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 2012;120(14):2807–16.PubMedCrossRefGoogle Scholar
  18. 18.
    Gandemer V, Chevret S, Petit A, Vermylen C, Leblanc T, Michel G, et al. Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol. Haematologica. 2012;97(11):1743–50.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Krentz S, Hof J, Mendioroz A, Vaggopoulou R, Dörge P, Lottaz C, et al. Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia. Leukemia. 2013;27(2):295.PubMedCrossRefGoogle Scholar
  20. 20.
    Hof J, Krentz S, van Schewick C, Körner G, Shalapour S, Rhein P, et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol. 2011;29(23):3185–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Irving JAE, Enshaei A, Parker CA, Sutton R, Kuiper RP, Erhorn A, et al. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2016;128(7):911–22.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Dworzak MN, Fröschl 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(6):1952–8.PubMedCrossRefGoogle Scholar
  23. 23.
    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(8):2961–6.CrossRefGoogle Scholar
  24. 24.
    Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL. 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(12):5457–85.CrossRefGoogle Scholar
  25. 25.
    Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer MA, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Eckert C, von Stackelberg A, Seeger K, Groeneveld T, Peters C, Klingebiel T, et al. Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia – long-term results of trial ALL-REZ BFM P95/96. Eur J Cancer. 2013;49(6):1346–55.PubMedCrossRefGoogle Scholar
  27. 27.
    Parker C, Krishnan S, Hamadeh L, Irving JAE, Kuiper RP, Révész T, et al. Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial. Lancet Haematol. 2019;6(4):e204–16.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Paganin M, Zecca M, Fabbri G, Polato K, Biondi A, Rizzari C, et al. Minimal residual disease is an important predictive factor of outcome in children with relapsed ‘high-risk’ acute lymphoblastic leukemia. Leukemia. 2008;22(12):2193.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Karawajew L, Dworzak M, Ratei R, Rhein P, Gaipa G, Buldini B, et al. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia. Haematologica. 2015;100(7):935–44.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Bader P, Kreyenberg H, Henze GHR, Eckert C, Reising M, Willasch A, et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM study group. J Clin Oncol. 2008;27(3):377–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grümayer R, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013;31(21):2736–42.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Reismüller B, Attarbaschi A, Peters C, Dworzak MN, Pötschger U, Urban C, et al. Long-term outcome of initially homogenously treated and relapsed childhood acute lymphoblastic leukaemia in Austria stem-cell trans-based report of the Austrian Berlin-Frankfurt-Münster (BFM) study group. Br J Haematol. 2009;144(4):559–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Ko RH, Ji L, Barnette P, Bostrom B, Hutchinson R, Raetz E, et al. Outcome of patients treated for relapsed or refractory acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia consortium study. J Clin Oncol. 2009;28(4):648–54.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hagedorn N, Acquaviva C, Fronkova E, von Stackelberg A, Barth A, zur Stadt U, et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of “isolated” and its possible clinical implications, a collaborative study of the resistant disease Committee of the International BFM study group. Blood. 2007;110(12):4022–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Pui C-H, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol. 2008;9(3):257–68.PubMedCrossRefGoogle Scholar
  36. 36.
    Barredo JC, Devidas M, Lauer SJ, Billett A, Marymont M, Pullen J, et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J Clin Oncol. 2006;24(19):3142–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Masurekar AN, Parker CA, Shanyinde M, Moorman AV, Hancock JP, Sutton R, et al. Outcome of central nervous system relapses in childhood acute lymphoblastic leukaemia--prospective open cohort analyses of the ALLR3 trial. PLoS One. 2014;9(10):e108107.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Eapen M, Zhang MJJ, Devidas M, Raetz E, Barredo JC, Ritchey AK, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's oncology group and the Center for International Blood and Marrow Transplant Research. Leukemia. 2008;22(2):281–6.PubMedCrossRefGoogle Scholar
  39. 39.
    van den Berg H, Langeveld NE, Veenhof CHN, Behrendt H. Treatment of isolated testicular recurrence of acute lymphoblastic leukemia without radiotherapy. Cancer. 1997;79(11):2257–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Berg H, Langeveld NE, Veenhof CHN, Behrendt H. Treatment of isolated testicular recurrence of acute lymphoblastic leukemia without radiotherapy: report from the Dutch late effects study group. Cancer. 1997;79(11):2257–62.PubMedCrossRefGoogle Scholar
  41. 41.
    Eapen M, Raetz E, Zhang M-J, 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(12):4961–7.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Uderzo C, Valsecchi MG, Bacigalupo A, Meloni G, Messina C, Polchi P, 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(2):352–8.PubMedCrossRefGoogle Scholar
  43. 43.
    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(10):3835–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Leung W, Pui C-H, Coustan-Smith E, Yang J, Pei D, Gan K, et al. Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia. Blood. 2012;120(2):468–72.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28(23):3730–8.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Bertaina A, Zecca M, Buldini B, Sacchi N, Algeri M, Saglio F, et al. Unrelated donor vs HLA-haploidentical α/β T-cell- and B-cell-depleted HSCT in children with acute leukemia. Blood. 2018;132(24):2594–607.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Sano H, Mochizuki K, Kobayashi S, Ohara Y, Ito M, Waragai T, et al. T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia. Int J Hematol. 2018;108(1):76–84.PubMedCrossRefGoogle Scholar
  48. 48.
    Kobayashi S, Ito M, Sano H, Mochizuki K, Akaihata M, Waragai T, et al. T-cell-replete haploidentical stem cell transplantation is highly efficacious for relapsed and refractory childhood acute leukaemia. Transfus Med. 2014;24(5):305–10.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–9.CrossRefGoogle Scholar
  50. 50.
    Bhojwani D, Sposto R, Shah NN, Rodriguez V, Yuan C, Stetler-Stevenson M, et al. Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2019;33(4):884–92.PubMedCrossRefGoogle Scholar
  51. 51.
    Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Messinger YH, Gaynon PS, Sposto R, van der Giessen J, Eckroth E, Malvar J, et al. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: therapeutic advances in Childhood Leukemia & Lymphoma (TACL) study. Blood. 2012;120(2):285–90.PubMedCrossRefGoogle Scholar
  53. 53.
    Horton TM, Whitlock JA, Lu X, O'Brien MM, Borowitz MJ, Devidas M, et al. Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's oncology group. Br J Haematol. 2019;186(2):274–85.. [Epub ahead of print]PubMedGoogle Scholar
  54. 54.
    Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24(12):1917–23.PubMedCrossRefGoogle Scholar
  55. 55.
    Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, et al. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011;118(23):6043–9.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, 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(15):3376–82.PubMedCrossRefGoogle Scholar
  57. 57.
    Commander LA, Seif AE, Insogna IG, Rheingold SR. Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma. Br J Haematol. 2010;150(3):345–51.PubMedCrossRefGoogle Scholar
  58. 58.
    Löffler A, Gruen M, Wuchter C, Schriever F, Kufer P, Dreier T, et al. Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Leukemia. 2003;17(5):900–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, Hanakam F, et al. Extremely potent, rapid and co-stimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer. 2002;100(6):690–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Hoffmann P, Hofmeister R, Brischwein K, Brandl C, Crommer S, Bargou R, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer. 2005;115(1):98–104.PubMedCrossRefGoogle Scholar
  61. 61.
    Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66.PubMedCrossRefGoogle Scholar
  62. 62.
    Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera J-M, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    DiJoseph JF, Armellino DC, Boghaert ER, Khandke K, Dougher MM, Sridharan L, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004;103(5):1807–14.PubMedCrossRefGoogle Scholar
  64. 64.
    Hinman LM, Hamann PR, Wallace R, Menendez AT, Durr FE, Upeslacis J. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res. 1993;53(14):3336–42.PubMedGoogle Scholar
  65. 65.
    Shor B, Gerber H-P, Sapra P. Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies. Mol Immunol. 2015;67(2):107–16.PubMedCrossRefGoogle Scholar
  66. 66.
    Hanna R, Ong GL, Mattes MJ. Processing of antibodies bound to B-cell lymphomas and other hematological malignancies. Cancer Res. 1996;56(13):3062–8.PubMedGoogle Scholar
  67. 67.
    Bouchard H, Viskov C, Garcia-Echeverria C. Antibody–drug conjugates—a new wave of cancer drugs. Bioorg Med Chem Lett. 2014;24(23):5357–63.PubMedCrossRefGoogle Scholar
  68. 68.
    Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517–28.PubMedCrossRefGoogle Scholar
  71. 71.
    Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent to treat leukemia remission by CD19CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322–31.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Jeha S, Gandhi V, Chan K, McDonald L, Ramirez I, Madden R, et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103(3):784–9.PubMedCrossRefGoogle Scholar
  73. 73.
    O’Connor D, Sibson K, Caswell M, Connor P, Cummins M, Mitchell C, et al. Early UK experience in the use of clofarabine in the treatment of relapsed and refractory paediatric acute lymphoblastic leukaemia. Br J Haematol. 2011;154(4):482–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Locatelli F, Testi AM, Bernardo M, Rizzari C, Bertaina A, Merli P, et al. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009;147(3):371–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Dunsmore KP, Devidas M, Linda SB, Borowitz MJ, Winick N, Hunger SP, et al. Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: a report from the children's oncology group. J Clin Oncol. 2012;30(22):2753–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Crombet O, Lastrapes K, Zieske A, Morales-Arias J. Complete morphologic and molecular remission after introduction of dasatinib in the treatment of a pediatric patient with t-cell acute lymphoblastic leukemia and ABL1 amplification. Pediatr Blood Cancer. 2012;59(2):333–4.PubMedCrossRefGoogle Scholar
  77. 77.
    Glover JM, Loriaux M, Tyner JW, Druker BJ, Chang BH. In vitro sensitivity to dasatinib in lymphoblasts from a patient with t(17;19) (q22;p13) gene rearrangement pre-B acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59(3):576–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Goto H. Childhood relapsed acute lymphoblastic leukemia: biology and recent treatment progress. Pediatr Int. 2015;57(6):1059–66.PubMedCrossRefGoogle Scholar
  79. 79.
    Bassan R, Bourquin J-P, DeAngelo DJ, Chiaretti S. New approaches to the management of adult acute lymphoblastic leukemia. J Clin Oncol. 2018;36:3504–19.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Ayumu Arakawa
    • 1
  1. 1.Department of Pediatric OncologyNational Cancer Center HospitalChuo-kuJapan

Personalised recommendations