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Advancements in the treatment of adult acute lymphoblastic leukaemia


Authors: Š. Hrabovský 1;  F. Folber 1;  C. Šálek 3;  J. M. Horáček 4;  J. Mayer 1,2;  M. Doubek 1,2
Authors‘ workplace: Interní hematologická a onkologická klinika, LF MU a FN Brno 1;  Středoevropský technologický institut (CEITEC), LF MU Brno 2;  Ústav hematologie a krevní transfuze, Praha 3;  IV. interní hematologická klinika, FN Hradec Králové a Katedra vojenského vnitřního lékařství a vojenské hygieny, FVZ UO Hradec Králové 4
Published in: Transfuze Hematol. dnes,21, 2015, No. 2, p. 84-91.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Acute lymphoblastic leukaemia (ALL) is predominantly a childhood disease and its incidence in adults is low. The prognosis and treatment outcome in adults are less satisfactory than in children. However, many new discoveries have been made recently. This review describes diagnostic procedures and treatment options in adult ALL. It focuses on minimal residual disease and its prognostic significance; on several new genetic abnormalities, such as IKZF1 (Ikaros) and NOTCH1 gene mutations and on the new prognostic categories of Ph-like (BCR-ABL1-like) ALL and early T-cell precursor (ETP) ALL. An overview of new drugs currently being tested in clinical trials, especially monoclonal antibodies and antibody-drug conjugates, is also presented.

Key words:
acute lymphoblastic leukaemia, minimal residual disease, BCR-ABL-like ALL, Ikaros, NOTCH1, ETP-ALL, monoclonal antibodies


Sources

1. Cole, CH. Lessons from 50 years of curing childhood leukaemia. J Paediatr Child Health 2015; 51(1): 78–81.

2. Šálek C, Šponerová D, Soukupová Maaloufová J. Akutní lymfoblastová leukemie: historie a současnost. Vnitř Lék 2012; 58 (Suppl 2): 20–26.

3. Brüggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood 2006; 107(3): 1116–1123.

4. Bassan R, Spinelli O, Oldani E, et al. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood 2009; 113(18): 4153–4162.

5. Patel B, Rai L, Buck G, et al. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol 2010; 148(1): 80–89.

6. Šálek C, Folber F, Froňková E, et al. Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia. [V recenzním řízení].

7. Bar M, Wood BL, Radich JP, et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leuk Res Treatment 2014; 2014: 421723. Publikováno elektronicky 23. března 2014. DOI: 10.1155/2014/421723.

8. Sutton R, Shaw PJ, Venn NC, et al. Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia. Br J Haematol 2015; 168(3): 395–404.

9. Den Boer ML, van Slegtenhorst M, De Menezes RX, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009; 10: 125–134.

10. Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinaseactivating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 2014; 371: 1005–1015.

11. Burmeister T, Schwartz S, Bartram CR, et al. Patients‘ age and BCR--ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 2008; 112: 918–919.

12. Izraeli S. Beyond Philadelphia: ‘Ph-like’ B cell precursor acute lymphoblastic leukemias – diagnostic challenges and therapeutic promises. Curr Opin Hematol 2014; 21(4): 289–296.

13. Tal N, Shochat C, Geron I, et al. Interleukin 7 and thymic stromal lymphopoietin: from immunity to leukemia. Cell Mol Life Sci 2014; 71(3): 365–378.

14. Roberts KG, Morin RD, Zhang J, et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 2012; 22: 153–166.

15. Li Y, Payne-Turner D, Harvey RC, et al. Genomic characterization and experimental modeling of BCR-ABL1-like acute lymphoblastic leukemia. Blood 2013; 122: 232.

16. Patterer V, Schnittger S, Kern W, et al. Hematologic malignancies with PCM1-JAK2 gene fusion share characteristics with myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1. Ann Hematol 2013; 92: 759–769.

17. Lilljebjorn H, Agerstam H, Orsmark-Pietras C, et al. RNA-seq identifies clinically relevant fusion genes in leukemia including a novel MEF2D/CSF1R fusion responsive to imatinib. Leukemia 2014; 28: 977–979.

18. Olsson L, Castor A, Behrendtz M, et al. Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2100. Leukemia 2014; 28: 302–310.

19. Palmi C, Valsecchi MG, Longinotti G, et al. What is the relevance of Ikaros gene deletions as a prognostic marker in pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia? Haematologica 2013; 98: 1226–1231.

20. Zaliova M, Zimmermannova O, Dorge P, et al. ERG deletion is associated with CD2 and attenuates the negative impact of IKZF1 deletion in childhood acute lymphoblastic leukemia. Leukemia 2014; 28: 182–185.

21. Joshi I, Yoshida T, Jena N, et al. Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia. Nat Immunol 2014; 15: 294–304.

22. Kobayashi K, Miyagawa N, Mitsui K, et al. TKI dasatinib monotherapy for a patient with Ph-like ALL bearing ATF7IP/PDGFRB translocation. Pediatr Blood Cancer 2014; publikováno elektronicky 14. listopadu 2014. DOI: 10.1002/pbc.25327.

23. Weston BW, Hayden MA, Roberts KG, et al. Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1--PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol 2013; 31: e413–e416.

24. Lengline E, Beldjord K, Dombret H, et al. Successful tyrosine kinase inhibitor therapy in a refractory B-cell precursor acute lymphoblastic leukemia with EBF1-PDGFRB fusion. Haematologica 2013; 98: e146–e148.

25. Maude SL, Tasian SK, Vincent T, et al. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 2012; 120: 3510–3518.

26. Breit S, Stanulla M, Flohr T, et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 2006; 108(4): 1151–1157.

27. Ferrando AA. NOTCH mutations as prognostic markers in T-ALL. Leukemia 2010; 24(12): 2003–2004.

28. Natarajan V, Bandapalli OR, Rajkumar T, et al. NOTCH1 and FBXW7 mutations favor better outcome in pediatric South Indian T-cell acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2015; 37(1): e23–e30.

29. Purow B. Notch inhibition as a promising new approach to cancer therapy. Adv Exp Med Biol 2012; 727: 305–319.

30. Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012; 481(7380): 157–163.

31. Neumann M, Greif PA, Baldus CD. Mutational landscape of adult ETP-ALL. Oncotarget 2013; 4(7): 954–955.

32. Haydu JE, Ferrando AA. Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP T-ALL). Curr Opin Hematol 2013; 20(4): 10.

33. Chopra A, Bakhshi S, Pramanik SK, et al. Immunophenotypic analysis of T-acute lymphoblastic leukemia. A CD5-based ETP-ALL perspective of non-ETP T-ALL. Eur J Haematol 2014; 92(3): 211–218.

34. Neumann M, Heesch S, Gökbuget N, et al. Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations. Blood Cancer J 2012; 2(1): e55.

35. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009; 10(2): 147–156.

36. Thomas DA, O’Brien S, Jorgensen JL, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood 2009; 113(25): 6330–6337.

37. 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: 77–78.

38. Jabbour E, Kantarjian H, Thomas D, et al. Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD-20 positive acute lymphoblastic leukemia (ALL). Blood 2013; 122(21): 2664.

39. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370(12): 1101–1110.

40. Tiwari AA, Ayello J, van de Ven C, et al. Obinutuzumab (GA101) significantly increases overall survival against CD20+ rituximab-sensitive and -resistant Burkitt (BL) and acute lymphoblastic leukemia (B-ALL): potential targeted therapy in patients with high risk BL and pre-B-ALL. AACR Annual Meeting 2014; Abstract 2902.

41. Gorin NC, Isnard F, Garderet L, et al. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study. Eur J Haematol 2013; 91(4): 315–321.

42. 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 ADVL04P2. Blood (ASH Annual Meeting Abstracts) 2011; 118: 573.

43. Advani AS, McDonough S, Coutre S, et al. SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia. Br J Haematol 2014; 165(4): 504–509.

44. Jain N, O’Brien S, Thomas D, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) as frontline therapy for older patients (≥60 years) with acute lymphoblastic leukemia (ALL). Blood (ASH Annual Meeting Abstracts) 2013; 122: 1432.

45. Kantarjian H, Thomas D, Jorgensen J, et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol 2012; 13(4): 403–411.

46. Topp MS, Gökbuget 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; publikováno elektronicky 15. prosince 2014. DOI: 10.1016/S1470-2045(14)71170-2.

47. Topp MS, Gökbuget N, Zugmaier G, 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): 4134–4140.

48. Orietta S, Manuela T, Barbara P, et al. Prognostic significance and treatment implications of minimal residual disease studies in Philadelphia-negative adult acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis 2014; 6(1): e2014062.

49. Zhao Y, Huang H, Wei G. Novel agents and biomarkers for acute lymphoid leukemia. J Hematol Oncol 2013; 6: 40.

50. Ai J, Advani A. Current status of antibody therapy in ALL. Br J Haematol 2015; 168(4): 471–480.

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Haematology Internal medicine Clinical oncology
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