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Novel Therapeutic Strategies in Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemias (K Ballen, Section Editor)
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Abstract

Chemotherapy cures only a minority of adult patients with acute lymphoblastic leukemia (ALL). In addition, relapsed ALL has a poor outcome with 5-year survival as low as 7 %. Hence, there is a need to develop effective therapies to treat relapsed disease and to combine these agents with chemotherapy to improve outcomes in newly diagnosed patients. ALL cells express several antigens amenable to target therapies including CD19, CD20, CD22, and CD52. Over the last decade, there has been a surge in the development of immune therapies which target these receptors and that have induced robust responses. In this manuscript, we review these novel immune agents in the treatment of B-ALL. As these new therapies mature, the challenge going forward will be to find safe and effective combinations of these agents with chemotherapy and to determine their place in the current treatment schema.

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References

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  1. Howlader N NA, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, et al., editors. SEER Cancer Statistics Review, 1975-2012. Bethesda: National Cancer Institute; 2015.

    Google Scholar 

  2. Pui CHRM, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004;350(15):1535–48.

    Article  CAS  PubMed  Google Scholar 

  3. Larson RA, Dodge RK, Linker CA, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood. 1998;92(5):1556–64.

    CAS  PubMed  Google Scholar 

  4. Kantarjian H, Thomas D, O’Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101(12):2788–801.

    Article  CAS  PubMed  Google Scholar 

  5. Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–15.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hoelzer D, Walewski J, Dohner H, et al. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter study. Blood. 2014;124:3870–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thomas DA, Faderl S, O’Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106(7):1569–80.

    Article  CAS  PubMed  Google Scholar 

  8. Fielding AK, Rowe J, Buck G, et al. UKALLXΙΙ/ECOG 2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014;123:843–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ravandi F, O’Brien S, Thomas D, et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010;116(12):2070–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tavernier E, Boiron JM, Huguet F, GET-LALA Group, Swiss Group for Clinical Cancer Research SAKK, Australasian Leukaemia and Lymphoma Group, et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia. 2007;21(9):1907–14.

    Article  CAS  PubMed  Google Scholar 

  11. Thomas DA, Kantarjian H, Smith TL, et al. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer. 1999;86(7):1216–30.

    Article  CAS  PubMed  Google Scholar 

  12. Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102(7):2379–86.

    Article  CAS  PubMed  Google Scholar 

  13. DeAngelo D et al. A phase II study of 2 -amino-9 Β−D-arabinosy−6-methoxy-9H-purine (506U78) in patients with relapsed or refractory T-lineage acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL): CALGB study 1980 I [abstract]. Blood. 2002;100:198a.

    Google Scholar 

  14. O’Brien S, Schiller G, Lister J, et al. High dose vincristine sulfate liposome injection for advanced, relapsed and refractory adult Philadelphia chromosome negative lymphoblastic leukemia. J Clin Oncol. 2013;31(6):676–83.

    Article  PubMed  Google Scholar 

  15. Thomas DA, O’Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010;28(24):3880–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hoelzer D, Huettmann A, Kaul F, et al. Immunochemotherapy with rituximab improves molecular CR rate and outcome in CD20+ B-lineage standard and high risk patients; results of 263 CD20+patients studied prospectively in GMALL study 07/2003. Blood. 2010;116(1):abstract 170.

    Google Scholar 

  17. Maury SCS, Thomas X, Heim D, Leguay T, Huguet F, et al. Addition of rituximab improves the outcome of adult patients with CD20-positive, Ph-negative, b-cell precursor acute lymphoblastic leukemia (BCP-ALL): results of the randomized Graall-R 2005 study. Blood. 2015;126(23 ( abstract)):1–1. This abstract at the ASH 2015 meeting, concludes that in adults with CD20 positive ALL, the addition of rituximab to standard intensive chemotherapy is well tolerated, significantly improves EFS, prolongs OS of patients not receiving allogeneic HSCT in first CR. Hence, adding rituximab to standard therapy should be considered as standard of care for these patients.

  18. Jabbour E, Kantarjian H, Thomas D, et al. Phase II study of the hyper-CVAD regimen in combination with ofatumumab as front line therapy for adults with CD-20 positive acute lymphoblastic leukemia (ALL). Blood. 2014;124(21):5277.

    Google Scholar 

  19. Raetz EA, Cairo MS, Borowitz MJ, et al. Reinduction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL) in children, adolescents and young adults: results from Children’s Oncology Group (COG) study ADVLO4P2. Blood. 2011;118:abstract 573.

    Google Scholar 

  20. Advani A, McDonough S, Coutre S, et al. Southwest Oncology Group Study S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukemia. Br J Haematol. 2014;165(4):504–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. deVries JF, Zwann CM, De Bie M, et al. The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells. Leukemia. 2012;26:255–64.

    Article  CAS  Google Scholar 

  22. Kantarjian H, Thomas D, Jorgensen, et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphoblastic leukemia: a phase 2 study. Lancet Oncol. 2012;13(4):403–11.

    Article  CAS  PubMed  Google Scholar 

  23. Kantarjian H, Thomas D, Jorgensen J, et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013;119(15):2728–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. DeAngelo DJ, Stock W, Shustov AR, et al. Weekly inotuzumab ozogamicin (InO) in adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL). Blood. 2013;122(21):3906.

    Google Scholar 

  25. DeAngelo DJ, Stelljes M, Martinelli G, et al. Efficacy and safety of inotuzumab ozogamicin (INO) vs standard of care (SOC) in salvage 1 or 2 patients with acute lymphoblastic leukemia (ALL): An ongoing global phase 3 study. 2015.

    Google Scholar 

  26. Jabbour E, O’Brien S, Nitin J, et al. Inotuzumab ozogamicin (IO) in combination with low-intensity chemotherapy as frontline therapy for older patients and as salvage therapy for adult with relapse/refractory acute lymphoblastic leukemia. J Clin Oncol. 2014;32:abstract 7019. This study concludes Mini Hyper CVD with IO is effective in patients over 60 years of age, with low mortality rate and 1 year OS of 81% and PFS of 96%, thereby indicating its use in the frontline setting in older patients with ALL and as a salvage approach (ORR-75%).

  27. DiJoseph JF, Dougher MM, Evans DY, Zhou BB, et al. Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-specific immunoconjugate of calecheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP. Cancer Chemother Pharmacol. 2011;67(4):741–9.

    Article  CAS  PubMed  Google Scholar 

  28. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin’s lymphoma: results of a phase I study. J Clin Oncol. 2010;28(12):2085–93.

    Article  CAS  PubMed  Google Scholar 

  29. Kebriaei P, Wilhelm K, Ravandi F, et al. Feasibility of allografting in patients with advanced acute lymphoblastic leukemia after salvage therapy with inotuzumab ozogamicin. Clin Lymphoma Myeloma Leuk. 2013;13(3):296–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Johnson DB, Savani BN. How can we reduce hepatic veno-occlusive disease-related deaths after allogeneic stem cell transplantation? Exp Hematol. 2012;40:513–7.

    Article  PubMed  Google Scholar 

  31. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood. 1998;92(10):3599–604.

    CAS  PubMed  Google Scholar 

  32. Ganem G, Saint-Marc Girardin MF, Kuentz M, et al. Venocclusive disease of the liver after allogeneic bone marrow transplantation in man. Int J Radiat Oncol Biol Phys. 1988;14(5):879–84.

    Article  CAS  PubMed  Google Scholar 

  33. Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Biol Blood Marrow Transplant. 1999;5(5):306–15.

    Article  CAS  PubMed  Google Scholar 

  34. Wayne AS, Kreitman RJ, Findley HW, et al. Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial. Clin Cancer Res. 2010;16(6):1894–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wayne AS, Bhojwani D, Silverman LB, et al. A novel anti-CD22 immunotoxin, moxetumomab pasudotox:Phase I study in pediatric acute lymphoblastic leukemia (ALL). Blood. 2011;118(21):abstract 4977.

    Google Scholar 

  36. Carol H, Szymanska B, Evans K, et al. The anti-CD19 antibody-drug conjugate SAR3419 prevents hematolymphoid relapse postinduction therapy in preclinical models of pediatric acute lymphoblastic leukemia. Clin Cancer Res. 2013;19(7):1795–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Younes A, Kim S, Romaguera J, et al. Phase 1 multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B- cell lymhoma. J Clin Oncol. 2012;30(22):2776–82.

    Article  CAS  PubMed  Google Scholar 

  38. clinicaltrials.gov. SAR 3419 in acute lymphoblastic leukemia (MYRALL). 2014. Available at: www.clinicaltrials.gov (NCT01440179).

    Google Scholar 

  39. Fathi AT, Borate U, DeAngelo DJ, O’Brien MM, et al. A phase 1 study of denintuzumab mafodotin (SGN-CD19A0 in adults with relapsed or refractory B-lineage acute leukemia (B-ALL) and highly aggressive lymphoma. Blood. 2015;126(23):1328.

    Google Scholar 

  40. Herrera L, Bostrom B, Gore L, et al. A phase 1 study of combotox in pediatric patients with refractory B-lineage acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2009;31(12):936–41.

    Article  CAS  PubMed  Google Scholar 

  41. Schindler J, Gajavelli S, Ravandi F, et al. A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia. Br J Haematol. 2011;154(4):471–6.

    Article  CAS  PubMed  Google Scholar 

  42. Klinger M, Brandl C, Zugmaier G, Hijazi Y, et al. Immunopharmacologic responses of patients with B-lineage acute lymphoblastic leukemia to continous infusion of T cell engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012;119(26):6226–33.

    Article  CAS  PubMed  Google Scholar 

  43. Topp MS, Kufer P, Gokbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29(18):2493–8.

    Article  CAS  PubMed  Google Scholar 

  44. Gokbuget N, Dombret H, Bonifacio M, Reichle A, et al. Long term outcomes after Blinatumomab Treatment: Follow-up of a phase 2 study in patients (pts) with minimal residual disease (MRD) positive B-cell precursor acute lymphoblastic leukaemia: a multicenter, single arm, phase 2 study. Blood. 2015;126(23 ( abstract)):680.

    Google Scholar 

  45. Topp MS, Gokbuget N, Stein AS, 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. This multicenter trial shows single agent blinatumomab had good antileukemic activity in adult patients with relapsed or refractory B-precursor ALL characterized by negative prognostic factors.

    Article  CAS  PubMed  Google Scholar 

  46. Kantarjian H, Gokbuget N, O’Brien SM, Stein AS, Jia C, Forman S, et al. Factors influencing outcomes in patients (Pts) with relapsed/refractory b-precursor acute lymohoblastic leukemia (r/r ALL) treated with blinatumomab in a phase 2 study. J Clin Oncol. 2015;33(suppl):abstract 7057.

    Google Scholar 

  47. Topp MS, Gokbuget N, Zugmaier G, et al. Phase II trial of the anti CD 19 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.

    Article  CAS  PubMed  Google Scholar 

  48. Amgen Inc. Blincyto (blinatumomab) for injection, for intravenous use. Prescribing Information. Thousand Oaks, CA: Amgen; 2014

  49. Clinicaltrials.gov. Phase III Trial of Blinatumomab vs Investigator's Choice of Chemotherapy in Patients with Relapsed or Refractory All. Available at: www.clinicaltrials.gov.

  50. Sadelain M, Riviere I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer. 2003;3(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  51. Hollyman D, Stefanski J, Przybylowski M, et al. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother. 2009;32(2):169–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kochenderfer JN, Feldman SA, Zhao Y, et al. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother. 2009;32(7):689–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Milone MC, Fish JD, Carpenito C, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):1453–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brentjens RJ, Riviere I, Park JH, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118(18):4817–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra138.

    Article  Google Scholar 

  56. Davila ML, Riviere I, Wang X, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6(224):224ra225.

    Article  Google Scholar 

  57. Sadelain M, Brentjens R, Riviere I, Park J. CD19 CAR therapy for acute lymphoblastic leukemia. Am Soc Clin Oncol Educ Book. 2015;35:e360–3.

    Article  Google Scholar 

  58. Park JH, Riviere I, Wang X, Bernal Y, Purdon T, et al. Implications of minimal residual disease negative complete remission (MRD-CR) and allogeneic stem cell transplant on safety and clinical outcome of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed, Refractory B-Cell ALL. Blood. 2015;126(23):682.

    Google Scholar 

  59. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17. This study showed CART cell therapy against CD19 is effective in treating relapsed refractory ALL and is associated with high remission rates, even among patients for whom stem- cell transplantation has failed, and achieved durable remission upto 24 months.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lee DW, Kochenderfer J, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.

    Article  CAS  PubMed  Google Scholar 

  62. Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014;20(2):119–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Brown P, Levis M, Shurtleff S, Campana D, Downing J, Small D. FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression. Blood. 2005;105(2):812–20.

    Article  CAS  PubMed  Google Scholar 

  64. Brown P, Levis M, McIntyre E, et al. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia. 2006;20:1368–76.

    Article  CAS  PubMed  Google Scholar 

  65. Katz FE, Lovering RC, Bradley LA, et al. Expression of the X-linked agammaglobulinemia gene, btk in B-cell acute lymphoblastic leukemia. Leukemia. 1994;8(4):574–7.

    CAS  PubMed  Google Scholar 

  66. Gutierrez A, Sanda T, Grebliunaite R, et al. High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood. 2009;114(3):647–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cortes J, Thomas D, Koller C, et al. Phase I study of bortezomib in refractory or relapsed acute leukemias. Clin Cancer Res. 2004;10(10):3371–6.

    Article  CAS  PubMed  Google Scholar 

  68. Horton TM, Pati D, Plon SE, et al. A phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children’s Oncology Group study. Clin Cancer Res. 2007;13(5):1516–22.

    Article  CAS  PubMed  Google Scholar 

  69. Messinger YH, Gaynon P, Sposto R, 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;120:285–90.

    Article  CAS  PubMed  Google Scholar 

  70. Filicko-O’Hara J, Mookerjee B, Alpdogan O, et al. Phase II study of bortezomib, mitoxantrone, and etoposide in relapsed/refractory acute leukemias. Blood. 2010;116 Suppl 1:Abstract 2192.

  71. Moorman AV, Schwab C, Ensor HM, et al. IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. J Clin Oncol. 2012;30(25):3100–8.

    Article  PubMed  Google Scholar 

  72. Daigle SR, Olhava EJ, Therkelsen CA, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011;20(1):53–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Van Vlierberghe P, Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest. 2012;122(10):3398–406.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Jeong EG, Kim MS, Nam HK, et al. Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers. Clin Cancer Res. 2008;14(12):3716–21.

    Article  CAS  PubMed  Google Scholar 

  75. Saunders P, Cisterne A, Weiss J, et al. The mammalian target of rapamycin inhibitor RAD 001(everolimus) synergizes with chemotherapeutic agents, ionizing radiation and proteasome inhibitors in pre-B acute lymphocytic leukemia. Haematologica. 2011;96:69–77.

    Article  CAS  PubMed  Google Scholar 

  76. Roll JD, Reuther GW. CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer Res. 2010;70(19):7347–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bressanin D, Evangelisti C, Ricci F, Tabellini G, Chiarini F, Tazzari PL, et al. Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: Eliminating activity by targeting at different levels. Oncotarget. 2012;3(8):811–23.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Schult CDM, Glass A, et al. The dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic drugs exerts antiproliferative activity towards acute lymphoblastic leukemia. Anticancer Res. 2012;32:463–74.

    CAS  PubMed  Google Scholar 

  79. Neviani P, Santhanam R, Oaks JJ, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest. 2007;117(9):2408–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Garcia-Manero GTD, Rhytting ME, et al. Final report of a phase I trial of decitabine with or without HyperCVAD in relapsed acute lymphocytic leukemia (ALL). Blood. 2010;116(Suppl1):Abstract 867.

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Ajoy Dias, Saad J. Kenderian, and Gustavo F. Westin each declare no potential conflicts of interest.

Mark R. Litzow declares grant support from Amgen.

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Dias, A., Kenderian, S.J., Westin, G.F. et al. Novel Therapeutic Strategies in Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 11, 253–264 (2016). https://doi.org/10.1007/s11899-016-0326-1

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