Skip to main content

Advertisement

Log in

Treatment of Young Adults with Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemias (K Ballen, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Young adults with acute lymphoblastic leukemia are a distinctive category of patients, with substantial difference in disease biology and response to therapy; hence, they pose unique challenges and issues beyond those faced by children and older adults. Despite inferior survival compared to children, there is growing evidence to suggest that young adults have improved outcomes when treated with pediatric-based approaches. With better supportive care and toxicity management and multidisciplinary team and approach, we have made great improvement in outcomes of young adults with ALL. However, despite significant progress, patients with persistence of minimal residual disease have a poor prognosis. This review discusses current controversies in the management of young adults with ALL, outcomes following pediatric and adult protocols, and the role of allogeneic stem cell transplantation. We also explore recent advances in disease monitoring and highlight our approach to incorporation of novel therapies in the management of young adults with ALL.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • of Importance •• of major importance

  1. Stock W, et al. Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: results of cancer and leukemia group B study 19802. Cancer. 2013;119(1):90–8.

    Article  CAS  PubMed  Google Scholar 

  2. Kantarjian HM, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18(3):547–61.

    Article  CAS  PubMed  Google Scholar 

  3. Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood. 2015;125(24):3702–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burke ME, Albritton K, Marina N. Challenges in the recruitment of adolescents and young adults to cancer clinical trials. Cancer. 2007;110(11):2385–93.

    Article  PubMed  Google Scholar 

  5. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371(9617):1030–43.

    Article  CAS  PubMed  Google Scholar 

  6. Patrick K, et al. Outcome for children and young people with early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol. 2014;166(3):421–4.

    Article  CAS  PubMed  Google Scholar 

  7. Moorman AV, et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol. 2010;11(5):429–38.

    Article  CAS  PubMed  Google Scholar 

  8. •• Roberts KG, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–15. An important article describing the genomic landscape of adolescent and young adults with ALL.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Russell LJ, et al. IGH@ translocations are prevalent in teenagers and young adults with acute lymphoblastic leukemia and are associated with a poor outcome. J Clin Oncol. 2014;32(14):1453–62.

    Article  PubMed  Google Scholar 

  10. Kenderian S, Litzow M. Acute lymphoblastic leukemia in adolescents and young adults—from genomics to the clinics. Clinical Oncology in Adolescents and Young Adults. 2013;2013(3):49–62.

    Google Scholar 

  11. Pieters R, et al. Clinical relevance of in vitro drug resistance testing in childhood acute lymphoblastic leukemia: the state of the art. Med Pediatr Oncol. 1994;22(5):299–308.

    Article  CAS  PubMed  Google Scholar 

  12. Raetz EA, et al. Cytogenetic and early-response characteristics of adolescents and young adults with acute lymphoblastic leukemia (ALL): a Children’s Oncology Group (COG) study, in American Society of Clinical Oncology. Journal of Clinical Oncology. 2010.

  13. Bleyer A, Budd T, Montello M. Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials. Cancer. 2006;107(7 Suppl):1645–55.

    Article  PubMed  Google Scholar 

  14. Albritton KH, et al. Site of oncologic specialty care for older adolescents in Utah. J Clin Oncol. 2007;25(29):4616–21.

    Article  PubMed  Google Scholar 

  15. Stock W, et al. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B studies. Blood. 2008;112(5):1646–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Boissel N, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003;21(5):774–80.

    Article  PubMed  Google Scholar 

  17. de Bont JM, et al. Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia. 2004;18(12):2032–5.

    Article  PubMed  Google Scholar 

  18. Ramanujachar R, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007;48(3):254–61.

    Article  PubMed  Google Scholar 

  19. Gaynon PS, et al. Long-term results of the Children’s Cancer Group studies for childhood acute lymphoblastic leukemia 1983–2002: a Children's Oncology Group report. Leukemia. 2010;24(2):285–97.

    Article  CAS  PubMed  Google Scholar 

  20. Moghrabi A, et al. Results of the Dana-Farber Cancer Institute ALL consortium protocol 95-01 for children with acute lymphoblastic leukemia. Blood. 2007;109(3):896–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cooper SL, Brown PA. Treatment of pediatric acute lymphoblastic leukemia. Pediatr Clin N Am. 2015;62(1):61–73.

    Article  Google Scholar 

  22. Pulsipher MA, Peters C, Pui CH. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant. 2011;17(1 Suppl):S137–48.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Barry E, et al. Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium protocols. J Clin Oncol. 2007;25(7):813–9.

    Article  CAS  PubMed  Google Scholar 

  24. Nachman JB, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med. 1998;338(23):1663–71.

    Article  CAS  PubMed  Google Scholar 

  25. DeAngelo D, Stevenson K, and Neuberg D. A multicenter phase II study using a dose intensified pegylated-asparginase pediatric regimen in adults with untreated acute lymphoblastic leukemia: a DFCI ALL Consortium trial, in American Society of Hematology. 2015.

  26. •• Stock W, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of U.S. Intergroup Trial C10403, in American Society of Hematology. Blood. 2014; 796. An important prospective trial establishing the safety and feasibility of pediatric regimen in adult with ALL.

  27. Ribera JM, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Español de Tratamiento en Hematología pediatric-based protocol ALL-96. J Clin Oncol. 2008;26(11):1843–9.

    Article  CAS  PubMed  Google Scholar 

  28. Huguet F, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–8.

    Article  CAS  PubMed  Google Scholar 

  29. Douer D, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–11.

    Article  CAS  PubMed  Google Scholar 

  30. Rijneveld AW, et al. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40. Leukemia. 2011;25(11):1697–703.

    Article  CAS  PubMed  Google Scholar 

  31. Advani AS. Perspectives and future directions for acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2016;16(Suppl):S6–9.

    Article  PubMed  Google Scholar 

  32. Egler RA, Ahuja SP, Matloub Y. L-Asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother. 2016;7(2):62–71.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Advani, A., et al., Frontline-treatment of acute lymphoblastic leukemia (ALL) in older adolescents and young adults (AYA) using a pediatric regimen is feasible: toxicity results of the prospective US Intergroup Trial C10403 (Alliance), in American Society of Hematology. Blood. 2013.

  34. •• Stock W, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma. 2011;52(12):2237–53. Guidelines on management of asparginase toxicity.

    Article  CAS  PubMed  Google Scholar 

  35. Vrooman LM, et al. Postinduction dexamethasone and individualized dosing of Escherichia coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study—Dana-Farber Cancer Institute ALL consortium protocol 00-01. J Clin Oncol. 2013;31(9):1202–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. DeAngelo DJ, et al. Long-term outcome of a pediatric-inspired regimen used for adults aged 18–50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015;29(3):526–34.

    Article  CAS  PubMed  Google Scholar 

  37. Aldoss I, et al. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia. Eur J Haematol. 2016;96(4):375–80.

    Article  CAS  PubMed  Google Scholar 

  38. Hunault-Berger M, et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica. 2008;93(10):1488–94.

    Article  CAS  PubMed  Google Scholar 

  39. Daver N, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. • Schultz KR, et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children’s Oncology Group study AALL0031. Leukemia. 2014;28(7):1467–71. Initial study evaluating the role of TKI in Ph+ ALL.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Thomas DA, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103(12):4396–407.

    Article  CAS  PubMed  Google Scholar 

  42. Ravandi F, et al. Multi-center US intergroup study of intensive chemotherapy plus dasatinib followed by allogeneic stem cell transplant in patients with Philadelphia chromosome positive acute lymphoblastic leukemia younger than 60, in American Society of Hematology. Blood. 2015; 796.

  43. Kim DY, et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015;126(6):746–56.

    Article  CAS  PubMed  Google Scholar 

  44. Koji S, et al. Updated results from phase II study of combination of hyper-CVAD (HCVAD) with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). In American Society of Clinical Oncology, J.o.C. Oncology, Editor. 2016.

  45. Ravandi F, et al. Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood. 2013;122(7):1214–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pfeifer H, et al. Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2007;110(2):727–34.

    Article  CAS  PubMed  Google Scholar 

  47. Soverini S, et al. Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis. Haematologica. 2011;96(4):552–7.

    Article  CAS  PubMed  Google Scholar 

  48. Fielding AK, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the international ALL trial MRC UKALLXII/ECOG2993. Blood. 2009;113(19):4489–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Litzow MR. Should anyone with Philadelphia chromosome-positive ALL who is negative for minimal residual disease receive a hematopoietic stem cell transplant in first remission? Best Pract Res Clin Haematol. 2016;29(4):345–50.

    Article  PubMed  Google Scholar 

  50. Roberts KG, et al. High frequency and poor outcome of Philadelphia chromosome-like acute lymphoblastic leukemia in adults. J Clin Oncol. 2017;35(4):394–401.

    Article  PubMed  Google Scholar 

  51. Iacobucci I, et al. Truncating erythropoietin receptor rearrangements in acute lymphoblastic leukemia. Cancer Cell. 2016;29(2):186–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ofran Y and Izraeli S. BCR-ABL (Ph)-like acute leukemia—pathogenesis, diagnosis and therapeutic options. Blood Rev. 2016.

  53. Zhang MJ, et al. Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee. Ann Intern Med. 1995;123(6):428–31.

    Article  CAS  PubMed  Google Scholar 

  54. •• Goldstone AH, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the international ALL trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111(4):1827–33. An important multinational trial evaluating the role of allogeneic stem cell transplant in patients with ALL.

    Article  CAS  PubMed  Google Scholar 

  55. Gupta V, et al. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood. 2013;121(2):339–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ram R, et al. Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric-inspired regimens: systematic review and meta-analysis. Am J Hematol. 2012;87(5):472–8.

    Article  PubMed  Google Scholar 

  57. Seftel MD, et al. Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. Am J Hematol. 2016;91(3):322–9.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Dombret H, et al. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014;9(2):158–64.

    Article  PubMed  Google Scholar 

  59. Beldjord K, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123(24):3739–49.

    Article  CAS  PubMed  Google Scholar 

  60. • Farhadfar N, Litzow MR. New monoclonal antibodies for the treatment of acute lymphoblastic leukemia. Leuk Res. 2016;49:13–21. A thorough review article on antibody based therapy for patients with ALL.

    Article  CAS  PubMed  Google Scholar 

  61. Nagorsen D, et al. Blinatumomab: a historical perspective. Pharmacol Ther. 2012;136(3):334–42.

    Article  CAS  PubMed  Google Scholar 

  62. • Maury S, et al. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med. 2016;375(11):1044–53. An important trial showing the efficacy of rituximab combined with chemotherapy in CD20-positive adult patients with ALL.

    Article  CAS  PubMed  Google Scholar 

  63. •• Kantarjian HM, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53. An important trial showing the superiority of inotuzumab ozogamicin over standard chemotherapy in relapsed/refractory ALL patients.

    Article  CAS  PubMed  Google Scholar 

  64. Topp M, et al. Blinatumomab improved overall survival in patients with relapsed or refractory Philadelphia negative B-cell precursor acute lymphoblastic leukemia in a randomized open label phase 3 study (TOWER), in European Society of Hematology. Haematologica. 2016.

  65. •• Kantarjian H, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47. An important trial showing the superiority of blinatumomab over standard chemotherapy in relapsed/refractory ALL patients.

    Article  PubMed  Google Scholar 

  66. Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016;127(26):3312–20.

    Article  CAS  PubMed  Google Scholar 

  67. Gardner R, et al. Decreased rates of severe CRS seen with early intervention strategies for CD 19 CAR-T cell toxicity management, in American Society of Hematology. Blood. 2016; 586.

  68. • Batlevi CL, et al. Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol. 2016;13(1):25–40. A recent review article on immunotherapies in ALL.

    Article  CAS  PubMed  Google Scholar 

  69. Maude SL, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Thomas DM, et al. Adolescent and young adult cancer: a revolution in evolution? Intern Med J. 2006;36(5):302–7.

    Article  CAS  PubMed  Google Scholar 

  71. Bleyer A. Young adult oncology: the patients and their survival challenges. CA Cancer J Clin. 2007;57(4):242–55.

    Article  PubMed  Google Scholar 

  72. Network, N.C.C. Clinical Practice Guidelines in Oncology Version 2.2016. January 1, 2017.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark Litzow.

Ethics declarations

Conflict of Interest

Ankit Kansagra declares no potential conflicts of interest. Mark Litzow reports a grant from Amgen.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Topical Collection on Acute Lymphocytic Leukemias

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kansagra, A., Litzow, M. Treatment of Young Adults with Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 12, 187–196 (2017). https://doi.org/10.1007/s11899-017-0377-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-017-0377-y

Keywords

Navigation