Current Hematologic Malignancy Reports

, Volume 13, Issue 2, pp 100–108 | Cite as

Recent Developments in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia

Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
  • 297 Downloads
Part of the following topical collections:
  1. Topical Collection on Acute Lymphocytic Leukemias

Abstract

Purpose of review

Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years.

Recent findings

The preponderance of data favors the treatment of AYA ALL patients with pediatric-inspired treatment regimens due to better relapse-free and overall survival. Minimal residual disease (MRD) measurement is emerging as an important prognostic factor and can serve as a new measure of efficacy of the addition of novel therapies to the treatment of patients with new diagnoses. There have been several treatment advances ranging from new cytotoxic agents for ALL to new antibody-based therapy to novel immune therapies such as CAR-T cells.

Summary

The care of AYA ALL patients is improving as the unique issues for this patient population are addressed.

Keywords

Acute lymphoblastic leukemia Adolescent and Young Adult (AYA) Augmented BFM treatment Novel therapy Minimal residual disease (MRD) Ph-like ALL 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights:

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

References

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

  1. 1.
    Stock W, La M, Sanford B, Bloomfield CB, Vardiman JW, Gaynon P, et al. What determined 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.  https://doi.org/10.1182/blood-2008-01-130237.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Stock W, Lugar SM, Advani AS, Geyer S, Harvey RC, Mullighan CG, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of U.S. Intergroup Trial C10403. Blood. 2014;124:21–796.CrossRefGoogle Scholar
  3. 3.
    Hough R, Rowntree C, Goulden N, Mitchell C, Moorman A, Wade R, et al. Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukemia: results from UKALL 2003. Br J Haematol. 2016;172(3):439–51.  https://doi.org/10.1111/bjh.13847.CrossRefPubMedGoogle Scholar
  4. 4.
    Seftel MD, Neuberg D, Zhang M-J, Wang H-L, Ballen KK, Bergeron J, et al. Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. Am J Hematol. 2015;91(3):322–9.  https://doi.org/10.1002/ajh.24285.CrossRefGoogle Scholar
  5. 5.
    Guzauskas GF, Villa KF, Vanhove GF, Fisher VL, Veenstra DL. Risk-benefit analysis of pediatric-inspired versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone protocols for acute lymphoblastic leukemia in adolescents and young adults. J Adolesc Young Adult Oncol. 2017;6(1):53–61.  https://doi.org/10.1089/jayao.2016.0049.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rytting ME, Jabbour EJ, Jorgensen JL, Ravandi F, Franklin AR, Kadia TM, et al. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen. Am J Hematol. 2016;91(8):819–23.  https://doi.org/10.1002/ajh.24419.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    • Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, et al. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children’s Oncology Group Study AALL0232. J Clin Oncol. 2016;34(20):2380–8.  https://doi.org/10.1200/JCO.2015.62.4544. This trial shows one of the challenges of adopting AYA approaches to adult medicine as the standard of care is always changing incrementally.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, et al. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children’s Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015;62(7):1176–83.  https://doi.org/10.1002/pbc.25470.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    • Muffly L, Lichtensztajn D, Shiraz P, Abrahao R, McNeer J, Stock W, et al. Adoption of pediatric-inspired acute lymphoblastic leukemia regimens by adult oncologists treating adolescents and young adults: a population-based study. Cancer. 2017;123(1):122–30.  https://doi.org/10.1002/cncr.30322. This article shows that despite the excitement generated by adopting pediatric-inspired ALL approaches to AYA patients, adoption of them to impact their care is lagging.CrossRefPubMedGoogle Scholar
  10. 10.
    • Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016.  https://doi.org/10.1056/NEJMoa1509277. This is an exciting new therapy which has manageable toxicity and is administratively patient friendly.
  11. 11.
    Topp MS, Gökbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32(36):4134–40.  https://doi.org/10.1200/JCO.2014.56.3247.CrossRefPubMedGoogle Scholar
  12. 12.
    Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017.  https://doi.org/10.1056/NEJMoa1609783.
  13. 13.
    Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35(16):1795–802.  https://doi.org/10.1200/JCO.2016.69.3531.CrossRefPubMedGoogle Scholar
  14. 14.
    Maury S, Chevret S, Thomas X, et al. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med 2016.  https://doi.org/10.1056/NEJMoa1605085.
  15. 15.
    Lee DW, Barrett DM, Mackall C, Orentas R, Grupp SA. The future is now: chimeric antigen receptors as new targeted therapies for childhood cancer. Clin Cancer Res. 2012;18(10):2780–90.  https://doi.org/10.1158/1078-0432.CCR-11-1920.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014.  https://doi.org/10.1056/NEJMoa1407222.
  17. 17.
    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.  https://doi.org/10.1016/S0140-6736(14)61403-3.CrossRefPubMedGoogle Scholar
  18. 18.
    Buechner J, Grupp SA, Maude SL, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): update to the interim analysis. Clin Lymphoma Myeloma Leuk. 2017;17:S263–4.  https://doi.org/10.1016/j.clml.2017.07.030.CrossRefGoogle Scholar
  19. 19.
    FDA. Press Announcements-FDA approval brings first gene therapy to the United States. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm. Accessed 8 Nov 2017.
  20. 20.
    O’Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013;31(6):676–83.  https://doi.org/10.1200/JCO.2012.46.2309.CrossRefPubMedGoogle Scholar
  21. 21.
    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 & Lympoma (TACL) study. Blood. 2012;120(2):285–90.  https://doi.org/10.1182/blood-2012-04-418640.CrossRefPubMedGoogle Scholar
  22. 22.
    Horton TM, Lu X, O'Brien MM, Borowitz MJ, Devidas M, Raetz EA, et al. AALL07P1: bortezomib with reinduction therapy for first relapse pre-BALL. 2013 Annual ASCO abstract #10003.Google Scholar
  23. 23.
    Cortes JE, Kim D-W, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783–96.  https://doi.org/10.1056/NEJMoa1306494.CrossRefPubMedGoogle Scholar
  24. 24.
    Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6.  https://doi.org/10.1002/cncr.30231.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Publ Gr. 2017;49(8):1211–8.  https://doi.org/10.1038/ng.3909.Google Scholar
  26. 26.
    Cave H, van der Werff ten Bosch J, Suciu S, Guidal C, Otten J, Bakkus M, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer—Childhood Leukemia Cooperative Group. N Engl J Med. 1998;339(9):591–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017;129(3):347–57.  https://doi.org/10.1182/blood-2016-07-726307.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Scherer F, Kurtz DM, Diehn M, Alizadeh AA. High-throughput sequencing for noninvasive disease detection in hematologic malignancies. Blood. 2017;130(4):440–52.  https://doi.org/10.1182/blood-2017-03-735639.CrossRefPubMedGoogle Scholar
  29. 29.
    Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14(3):199–209.  https://doi.org/10.1016/S1470-2045(12)70600-9.CrossRefPubMedGoogle Scholar
  30. 30.
    Ribera JM, Oriol A, Morgades M, Montesinos P, Sarra J, Gonzalez-Campos J, et al. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32(15):1595–604.  https://doi.org/10.1200/JCO.2013.52.2425.CrossRefPubMedGoogle Scholar
  31. 31.
    Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126(8):964–71.  https://doi.org/10.1182/blood-201-03-633685.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–15.  https://doi.org/10.1056/NEJMoa1403088.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500–10.  https://doi.org/10.1200/JCO.2013.49.2678.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Waheed A, Grover NS, Douvas MG. Fertility counseling in cancer patients: a study of patients and physicians. J Clin Oncol. 2015.  https://doi.org/10.1200/jco.2015.33.15_suppl.e177721.
  35. 35.
    Spencer HE, Kindwall-Keller TL, Smith RP, Thomas TD, Volodin L, et al. Lack of early oncofertility education in hematologic cancer patients potentially referable for HSCT. Biol Blood Marrow Transplant. 2015;S171–184.Google Scholar
  36. 36.
    Leblicq C, Laverdiere C, Decarie JC, Delisle JF, Isler MH, Moghrabi A, et al. Effectiveness of pamidronate as treatment of symptomatic osteonecrosis occurring in children treated for acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013;60(5):741–7.  https://doi.org/10.1002/pbc.24313.CrossRefPubMedGoogle Scholar
  37. 37.
    Kaste SC, Pei D, Cheng C, Neel MD, Bowman WP, Ribeiro RC, et al. Utility of early screening magnetic resonance imaging for extensive hip osteonecrosis in pediatric patients treated with glucocorticoids. J Clin Oncol. 2015;33(6):610–5.  https://doi.org/10.1200/JCO.2014.57.5480.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Elbarbary NS, Ismail EA, Farahat RK, El-Hamamsy M. Omega-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: a randomized placebo-controlled study. Nutrition. 2016;32(1):41–7.  https://doi.org/10.1016/j.nut.2015.06.010.CrossRefPubMedGoogle Scholar
  39. 39.
    Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Onc. 2016;34(8):854–62.  https://doi.org/10.1200/JCO.2015.60.8851.CrossRefGoogle Scholar
  40. 40.
    Conklin HM, Ogg RJ, Ashford JM, Scoggins MA, Zou P, Clark KN, et al. Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: a randomized controlled trial. J Clin Onc. 2015;33(33):3894–902.  https://doi.org/10.1200/JCO.2015.61.6672.CrossRefGoogle Scholar
  41. 41.
    Hooke MC, Gilchrist L, Tanner L, Hart N, Withycombe JS. Use of a fitness tracker to promote physical activity in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(4):684–9.  https://doi.org/10.1002/pbc.25860.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of Virginia Health SystemCharlottesvilleUSA
  2. 2.University of Virginia HospitalCharlottesvilleUSA

Personalised recommendations