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Management of Elderly Patients with Newly Diagnosed Chronic Myeloid Leukemia in the Accelerated or Blastic Phase

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Abstract

In the elderly population, the accelerated and blastic phases of chronic myeloid leukemia (CML) are difficult to treat, not just because of the higher chance of acquired mutations than in younger individuals, but because of additional associated co-morbidities. Tyrosine kinase inhibitors are well-established in the treatment of the chronic phase of CML, and their use in advanced phases is ever-increasing. Elderly patients who are still eligible candidates for transplant can undergo reduced-intensity transplants from related or unrelated donors after reverting to chronic phase. Post-transplantation, these patients require adequate monitoring and therapy to prevent relapses. Newer modalities of treatment or interventions are urgently required in this complex group of patients.

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References

  1. Goldman JM. Management of chronic myeloid leukaemia. Blood Rev. 1994;8(1):21–9.

    Article  CAS  PubMed  Google Scholar 

  2. Hehlmann R, Hochhaus A, Baccarani M, European L. Chronic myeloid leukaemia. Lancet. 2007;370(9584):342–50.

    Article  CAS  PubMed  Google Scholar 

  3. McWeeney SK, Pemberton LC, Loriaux MM, Vartanian K, Willis SG, Yochum G, et al. A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib. Blood. 2010;115(2):315–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302.

    Article  CAS  PubMed  Google Scholar 

  5. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood. 2012;120(7):1390–7.

    Article  CAS  PubMed  Google Scholar 

  6. Michor F, Iwasa Y, Nowak MA. The age incidence of chronic myeloid leukemia can be explained by a one-mutation model. Proc Natl Acad Sci USA. 2006;103(40):14931–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rohrbacher M, Berger U, Hochhaus A, Metzgeroth G, Adam K, Lahaye T, et al. Clinical trials underestimate the age of chronic myeloid leukemia (CML) patients. Incidence and median age of Ph/BCR-ABL-positive CML and other chronic myeloproliferative disorders in a representative area in Germany. Leukemia. 2009;23(3):602–4.

    Article  CAS  PubMed  Google Scholar 

  8. Berger U, Maywald O, Pfirrmann M, Lahaye T, Hochhaus A, Reiter A, et al. Gender aspects in chronic myeloid leukemia: long-term results from randomized studies. Leukemia. 2005;19(6):984–9.

    Article  CAS  PubMed  Google Scholar 

  9. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63.

    Article  PubMed  Google Scholar 

  10. Latagliata R, Breccia M, Carmosino I, Cannella L, De Cuia R, Diverio D, et al. “Real-life” results of front-line treatment with imatinib in older patients (>65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res. 2010;34(11):1472–5.

    Article  CAS  PubMed  Google Scholar 

  11. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63(4):789–99.

    CAS  PubMed  Google Scholar 

  12. Hasford J, Ansari H, Pfirrmann M, Hehlmann R. Analysis and validation of prognostic factors for CML. German CML Study Group. Bone Marrow Transplant. 1996;17(Suppl 3):S49–54.

    PubMed  Google Scholar 

  13. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118(3):686–92.

    Article  CAS  PubMed  Google Scholar 

  14. Gonsalves W, Ganti AK. Targeted anti-cancer therapy in the elderly. Crit Rev Oncol Hematol. 2011;78(3):227–42.

    Article  PubMed  Google Scholar 

  15. Wiggins CL, Harlan LC, Nelson HE, Stevens JL, Willman CL, Libby EN, et al. Age disparity in the dissemination of imatinib for treating chronic myeloid leukemia. Am J Med. 2010;123(8):764.e1–9.

  16. Bjorkholm M, Ohm L, Eloranta S, Derolf A, Hultcrantz M, Sjoberg J, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol. 2011;29(18):2514–20.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  CAS  PubMed  Google Scholar 

  18. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saussele S, Krauss MP, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, et al. Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV. Blood. 2015;126(1):42–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Breccia M, Latagliata R, Stagno F, Luciano L, Gozzini A, Castagnetti F, et al. Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib. Haematologica. 2011;96(10):1457–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011;29(12):1634–42.

    Article  CAS  PubMed  Google Scholar 

  22. Palandri F, Castagnetti F, Testoni N, Luatti S, Marzocchi G, Bassi S, et al. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. Haematologica. 2008;93(12):1792–6.

    Article  CAS  PubMed  Google Scholar 

  23. Cortes J, Talpaz M, O’Brien S, Giles F, Beth Rios M, Shan J, et al. Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer. 2003;98(6):1105–13.

    Article  CAS  PubMed  Google Scholar 

  24. Latagliata R, Breccia M, Carmosino I, Sarlo C, Montefusco E, Mancini M, et al. Elderly patients with Ph+ chronic myelogenous leukemia (CML): results of imatinib mesylate treatment [erratum appears in Leuk Res. 2005 Sep; 29(9):1099]. Leuk Res. 2005;29(3):287–91.

    Article  CAS  PubMed  Google Scholar 

  25. Ohanian M, Kantarjian HM, Quintas-Cardama A, Jabbour E, Abruzzo L, Verstovsek S, et al. Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid leukemia in accelerated phase. Clin Lymphoma Myeloma Leuk. 2014;14(2):155–62 e1.

  26. Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12(8):908–16.

    Article  PubMed  Google Scholar 

  27. Giles FJ, Mauro MJ, Hong F, Ortmann CE, McNeill C, Woodman RC, et al. Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis. Leukemia. 2013;27(6):1310–5.

    Article  CAS  PubMed  Google Scholar 

  28. le Coutre PD, Giles FJ, Hochhaus A, Apperley JF, Ossenkoppele GJ, Blakesley R, et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia. 2012;26(6):1189–94.

    Article  PubMed  Google Scholar 

  29. Giles FJ, Kantarjian HM, le Coutre PD, Baccarani M, Mahon FX, Blakesley RE, et al. Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia. 2012;26(5):959–62.

    Article  CAS  PubMed  Google Scholar 

  30. Le Coutre P, Rea D, Abruzzese E, Dombret H, Trawinska MM, Herndlhofer S, et al. Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst. 2011;103(17):1347–8.

    Article  PubMed  Google Scholar 

  31. Cortes J, Mauro M, Steegmann JL, Saglio G, Malhotra R, Ukropec JA, et al. Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: data from the FDA Adverse Event Reporting System. Am J Hematol. 2015;90(4):E66–72.

    Article  CAS  PubMed  Google Scholar 

  32. Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007;109(8):3207–13.

    Article  CAS  PubMed  Google Scholar 

  33. Apperley JF, Cortes JE, Kim DW, Roy L, Roboz GJ, Rosti G, et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol. 2009;27(21):3472–9.

    Article  CAS  PubMed  Google Scholar 

  34. Kantarjian H, Cortes J, Kim DW, Dorlhiac-Llacer P, Pasquini R, DiPersio J, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009;113(25):6322–9.

    Article  CAS  PubMed  Google Scholar 

  35. Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boque C, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123(4):494–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gambacorti-Passerini C, Kantarjian HM, Kim DW, Khoury HJ, Turkina AG, Brummendorf TH, et al. Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors. Am J Hematol. 2015;90(9):755–68.

    Article  CAS  PubMed  Google Scholar 

  37. Cortes JE, Kim DW, 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.

    Article  CAS  PubMed  Google Scholar 

  38. Cortes JE, Kim DG, Pinilla-Ibarz J, Le Coutre PD, Paquette R, Chuah C, et al. Efficacy and safety of ponatinib in heavily pretreated leukemia patients in the PACE trial: 3-year results [abstract no. e18052]. J Clin Oncol. 2015;33(Suppl).

  39. Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Epic: a phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CP-CML) [abstract]. Blood (American Society of Hematology abstracts). 2014;124(21):519.

    Google Scholar 

  41. Nicolini FE, Khoury HJ, Akard L, Rea D, Kantarjian H, Baccarani M, et al. Omacetaxine mepesuccinate for patients with accelerated phase chronic myeloid leukemia with resistance or intolerance to two or more tyrosine kinase inhibitors. Haematologica. 2013;98(7):e78–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cortes JE, Kantarjian HM, Rea D, Wetzler M, Lipton JH, Akard L, et al. Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: results with 24 months of follow-up. Cancer. 2015;121(10):1637–44.

    Article  CAS  PubMed  Google Scholar 

  43. Khoury HJ, Cortes J, Baccarani M, Wetzler M, Masszi T, Digumarti R, et al. Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors. Leuk Lymphoma. 2015;56(1):120–7.

    Article  CAS  PubMed  Google Scholar 

  44. Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, et al. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006;20(3):400–3.

    Article  CAS  PubMed  Google Scholar 

  45. Strati P, Kantarjian H, Thomas D, O’Brien S, Konoplev S, Jorgensen JL, et al. HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia. Cancer. 2014;120(3):373–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hilbe W, Apfelbeck U, Fridrik M, Bernhart M, Niessner H, Abbrederis K, et al. Interferon-alpha for the treatment of elderly patients with chronic myeloid leukaemia. Leuk Res. 1998;22(10):881–6.

    Article  CAS  PubMed  Google Scholar 

  47. Cortes J, Kantarjian H, O’Brien S, Robertson LE, Pierce S, Talpaz M. Result of interferon-alpha therapy in patients with chronic myelogenous leukemia 60 years of age and older. Am J Med. 1996;100(4):452–5.

    Article  CAS  PubMed  Google Scholar 

  48. Palandri F, Iacobucci I, Castagnetti F, Testoni N, Poerio A, Amabile M, et al. Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-alpha: 5-year outcome. Haematologica. 2008;93(5):770–4.

    Article  CAS  PubMed  Google Scholar 

  49. Sacchi S, Kantarjian HM, O’Brien S, Cortes J, Rios MB, Giles FJ, et al. Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients. Cancer. 1999;86(12):2632–41.

    Article  CAS  PubMed  Google Scholar 

  50. Schiffer CA, DeBellis R, Kasdorf H, Wiernik PH. Treatment of the blast crisis of chronic myelogenous leukemia with 5-azacitidine and VP-16-213. Cancer Treat Rep. 1982;66(2):267–71.

    CAS  PubMed  Google Scholar 

  51. Dutcher JP, Eudey L, Wiernik PH, Paietta E, Bennett JM, Arlin Z, et al. Phase II study of mitoxantrone and 5-azacytidine for accelerated and blast crisis of chronic myelogenous leukemia: a study of the Eastern Cooperative Oncology Group. Leukemia. 1992;6(8):770–5.

    CAS  PubMed  Google Scholar 

  52. Seymour JF, Kim DW, Rubin E, Haregewoin A, Clark J, Watson P, et al. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Cancer J. 2014;4:e238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gratwohl A, Brand R, Apperley J, Crawley C, Ruutu T, Corradini P, et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2006;91(4):513–21.

    PubMed  Google Scholar 

  54. Crawley C, Szydlo R, Lalancette M, Bacigalupo A, Lange A, Brune M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood. 2005;106(9):2969–76.

    Article  CAS  PubMed  Google Scholar 

  55. Bacher U, Klyuchnikov E, Zabelina T, Ottinger H, Beelen DW, Schrezenmeier H, et al. The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia—a report from the German Registry covering the period from 1998 to 2004. Ann Hematol. 2009;88(12):1237–47.

    Article  PubMed  Google Scholar 

  56. Khoury HJ, Kukreja M, Goldman JM, Wang T, Halter J, Arora M, et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis. Bone Marrow Transplant. 2012;47(6):810–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Deininger M, Schleuning M, Greinix H, Sayer HG, Fischer T, Martinez J, et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica. 2006;91(4):452–9.

    CAS  PubMed  Google Scholar 

  58. Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, et al. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood. 2010;115(10):1880–5.

    Article  CAS  PubMed  Google Scholar 

  59. Jabbour E, Cortes J, Kantarjian H, Giralt S, Andersson BS, Giles F, et al. Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity. Cancer. 2007;110(2):340–4.

    Article  CAS  PubMed  Google Scholar 

  60. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet. 1998;352(9134):1087–92.

    Article  CAS  PubMed  Google Scholar 

  61. Pavlu J, Kew AK, Taylor-Roberts B, Auner HW, Marin D, Olavarria E, et al. Optimizing patient selection for myeloablative allogeneic hematopoietic cell transplantation in chronic myeloid leukemia in chronic phase. Blood. 2010;115(20):4018–20.

    Article  CAS  PubMed  Google Scholar 

  62. Jiang H, Xu LP, Liu DH, Liu KY, Chen SS, Jiang B, et al. Allogeneic hematopoietic SCT in combination with tyrosine kinase inhibitor treatment compared with TKI treatment alone in CML blast crisis. Bone Marrow Transplant. 2014;49(9):1146–54.

    Article  CAS  PubMed  Google Scholar 

  63. Nicolini FE, Basak GW, Soverini S, Martinelli G, Mauro MJ, Muller MC, et al. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias. Blood. 2011;118(20):5697–700.

    Article  CAS  PubMed  Google Scholar 

  64. Fu Y, Fesler M, Mahmud G, Bernreuter K, Jia D, Batanian JR. Narrowing down the common deleted region of 5q to 6.0 Mb in blastic plasmacytoid dendritic cell neoplasms. Cancer Genet. 2013;206(7–8):293–8.

  65. Zheng C, Tang B, Yao W, Tong J, Zhu X, Song K, et al. Comparison of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in advanced stage. Biol Blood Marrow Transplant. 2013;19(12):1708–12.

    Article  CAS  PubMed  Google Scholar 

  66. Sanz J, Montesinos P, Saavedra S, Lorenzo I, Senent L, Planelles D, et al. Single-unit umbilical cord blood transplantation from unrelated donors in adult patients with chronic myelogenous leukemia. Biol Blood Marrow Transplant. 2010;16(11):1589–95.

    Article  PubMed  Google Scholar 

  67. Xiao-Jun H, Lan-Ping X, Kai-Yan L, Dai-Hong L, Huan C, Wei H, et al. HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase. Ann Med. 2008;40(6):444–55.

    Article  PubMed  Google Scholar 

  68. Elmaagacli AH, Beelen DW, Opalka B, Seeber S, Schaefer UW. The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow. Blood. 1999;94(2):384–9.

    CAS  PubMed  Google Scholar 

  69. Couban S, Messner HA, Andreou P, Egan B, Price S, Tinker L, et al. Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: a study of 29 patients. Biol Blood Marrow Transplant. 2000;6(4A):422–7.

    Article  CAS  PubMed  Google Scholar 

  70. Stem Cell Trialists’ Collaborative Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005;23(22):5074–87.

    Article  PubMed Central  Google Scholar 

  71. Schmitz N, Eapen M, Horowitz MM, Zhang MJ, Klein JP, Rizzo JD, et al. Long-term outcome of patients given transplants of mobilized blood or bone marrow: a report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. Blood. 2006;108(13):4288–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kebriaei P, Detry MA, Giralt S, Carrasco-Yalan A, Anagnostopoulos A, Couriel D, et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia. Blood. 2007;110(9):3456–62.

    Article  CAS  PubMed  Google Scholar 

  73. Topcuoglu P, Arat M, Ozcan M, Arslan O, Ilhan O, Beksac M, et al. Case-matched comparison with standard versus reduced intensity conditioning regimen in chronic myeloid leukemia patients. Ann Hematol. 2012;91(4):577–86.

    Article  PubMed  Google Scholar 

  74. Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, et al. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012;119(17):4083–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kaeda J, O’Shea D, Szydlo RM, Olavarria E, Dazzi F, Marin D, et al. Serial measurement of BCR-ABL transcripts in the peripheral blood after allogeneic stem cell transplantation for chronic myeloid leukemia: an attempt to define patients who may not require further therapy. Blood. 2006;107(10):4171–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Arpinati M, Tolomelli G, Bochicchio MT, Castagnetti F, Amabile M, Bandini G, et al. Molecular monitoring of BCR-ABL transcripts after allogeneic stem cell transplantation for chronic myeloid leukemia. Biol Blood Marrow Transplant. 2013;19(5):735–40.

    Article  CAS  PubMed  Google Scholar 

  77. Shanavas M, Messner HA, Kamel-Reid S, Atenafu EG, Gupta V, Kuruvilla J, et al. Molecular relapse after allogeneic hematopoietic cell transplant for chronic myeloid leukemia: some long-term survivors appear to tolerate even lack of major molecular response. Leuk Lymphoma. 2014;55(10):2398–401.

    Article  PubMed  Google Scholar 

  78. Heaney NB, Copland M, Stewart K, Godden J, Parker AN, McQuaker IG, et al. Complete molecular responses are achieved after reduced intensity stem cell transplantation and donor lymphocyte infusion in chronic myeloid leukemia. Blood. 2008;111(10):5252–5.

    Article  CAS  PubMed  Google Scholar 

  79. Olavarria E, Siddique S, Griffiths MJ, Avery S, Byrne JL, Piper KP, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110(13):4614–7.

    Article  CAS  PubMed  Google Scholar 

  80. Luo Y, Lai XY, Tan YM, Shi JM, Zhao YM, Han XY, et al. Reduced-intensity allogeneic transplantation combined with imatinib mesylate for chronic myeloid leukemia in first chronic phase. Leukemia. 2009;23(6):1171–4.

    Article  CAS  PubMed  Google Scholar 

  81. Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76(12):2462–5.

    CAS  PubMed  Google Scholar 

  82. Hess G, Bunjes D, Siegert W, Schwerdtfeger R, Ledderose G, Wassmann B, et al. Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study. J Clin Oncol. 2005;23(30):7583–93.

    Article  CAS  PubMed  Google Scholar 

  83. Weisser M, Tischer J, Schnittger S, Schoch C, Ledderose G, Kolb HJ. A comparison of donor lymphocyte infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation. Haematologica. 2006;91(5):663–6.

    CAS  PubMed  Google Scholar 

  84. Savani BN, Montero A, Kurlander R, Childs R, Hensel N, Barrett AJ. Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36(11):1009–15.

    Article  CAS  PubMed  Google Scholar 

  85. Kreuzer KA, Kluhs C, Baskaynak G, Movassaghi K, Dorken B, le Coutre P. Filgrastim-induced stem cell mobilization in chronic myeloid leukaemia patients during imatinib therapy: safety, feasibility and evidence for an efficient in vivo purging. Br J Haematol. 2004;124(2):195–9.

    Article  PubMed  Google Scholar 

  86. Pinilla-Ibarz J, Cathcart K, Korontsvit T, Soignet S, Bocchia M, Caggiano J, et al. Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood. 2000;95(5):1781–7.

    CAS  PubMed  Google Scholar 

  87. Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123(15):2343–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Frolova O, Benito J, Brooks C, Wang RY, Korchin B, Rowinsky EK, et al. SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia. Br J Haematol. 2014;166(6):862–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Jeffrey H. Lipton.

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U D. declares no conflict of interests. D. K. has served in an advisory capacity for and has received research funding from Novartis and BMS. J. H. L. has served in an advisory capacity for and has received research funding from Novartis, Pfizer, Ariad, Teva, and BMS.

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Deotare, U., Kim, D.D. & Lipton, J.H. Management of Elderly Patients with Newly Diagnosed Chronic Myeloid Leukemia in the Accelerated or Blastic Phase. Drugs Aging 33, 335–345 (2016). https://doi.org/10.1007/s40266-016-0351-8

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  • DOI: https://doi.org/10.1007/s40266-016-0351-8

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