Allogeneic stem cell transplantation for chronic myeloid leukemia

Current Hematologic Malignancy Reports

Volumn 8, Issue 1, 2013, Pages 43-51

  Pavlů, Jiří ^a   Apperley, Jane F ^a,b  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Allogeneic stem cell transplantation; BMT; Chronic myeloid leukemia; CML; Graft versus leukemia effect; TKI; Tyrosine kinase inhibitor

Indexed keywords

BCR ABL PROTEIN; BOSUTINIB; BUSULFAN; DASATINIB; IMATINIB; NILOTINIB; PONATINIB;

ACUTE LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER SURVIVAL; CHRONIC MYELOID LEUKEMIA; CORD BLOOD STEM CELL TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; DRUG DOSE COMPARISON; FAILURE FREE SURVIVAL; GRAFT VERSUS HOST REACTION; GRAFT VERSUS LEUKEMIA EFFECT; HUMAN; MINIMAL RESIDUAL DISEASE; MYELOABLATIVE CONDITIONING; NONHUMAN; OUTCOME ASSESSMENT; OVERALL SURVIVAL; RECURRENCE RISK; REDUCED INTENSITY CONDITIONING; T CELL DEPLETION; TREATMENT INDICATION; TREATMENT RESPONSE; WHOLE BODY RADIATION;

HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; NEOPLASM, RESIDUAL; STEM CELL TRANSPLANTATION; TRANSPLANTATION CONDITIONING; TRANSPLANTATION, HOMOLOGOUS;

EID: 84874232425     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-012-0149-7     Document Type: Article

References (89)

1. Geary CG. The story of chronic myeloid leukaemia. Br J Haematol. 2000;110:2-11.
2. Fefer A, Cheever MA, Thomas ED, et al. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med. 1979;300:333-7.
3. Pavlu J, Szydlo RM, Goldman JM, Apperley JF. Three decades of transplantation for chronic myeloid leukemia: what have we learned? Blood. 2011;117:755-7.
4. Barnes DW, Corp MJ, Loutit JF, Neal FE. Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication. Br Med J. 1956;2:626-7.
5. Graw Jr RG, Buckner CD, Whang-Peng J, et al. Complication of bone marrow transplantation. Graft-versus-host disease resulting from chronic myelogenous leukaemia leucocyte transfusions. Lancet. 1970;2:338-41.
6. Odom LF, August CS, Githens JH, et al. Remission of relapsed leukaemia during a graft-versus-host reaction. A "graft-versus-leukaemia reaction" in man? Lancet. 1978;2:537-40.
7. Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med. 1979;300:1068-73.
8. Apperley JF, Jones L, Hale G, et al. Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant. 1986;1:53-66.
9. Horowitz MM, Gale RP, Sondel PM, et al. Graft- versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555-62.
10. Ringden O, Zwaan F, Hermans J, Gratwohl A. European experience of bone marrow transplantation for leukemia. Transplant Proc. 1987;19:2600-4.
11. Fefer A, Sullivan KM, Weiden PL, et al. Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than syngeneic marrow transplantation. In: Truitt RL, Gale RP, Bortin MM, editors. Cellular immunotherapy of cancer. New York: A.R. Liss; 1987. p. 401-8.
12. Falkenburg JH, Wafelman AR, Joosten P, et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood. 1999;94:1201-8.
13. Molldrem J, Dermime S, Parker K, et al. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood. 1996;88:3223-9.
14. Molldrem JJ, Lee PP, Wang C, et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med. 2000;6:1018-23.
15. Rezvani K, Yong AS, Savani BN, et al. Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood. 2007;110:1924-32.
16. Rezvani K, Grube M, Brenchley JM, et al. Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation. Blood. 2003;102:2892-900.
17. Butt NM, Rojas JM, Wang L, et al. Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects. Haematologica. 2005;90:1315-23.
18. Yong AS, Stephens N, Weber G, et al. Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein. Leukemia. 2011;25:629-37.
19. • Bornhäuser M, Thiede C, Platzbecker U, et al. Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia. Blood. 2011;117:7174-84. Donor-derived dendritic cells generated in vitro were loaded with human leukocyte antigen-restricted peptides derived from PR1, WT1, and/or BCR-ABL and used to stimulate donor CD8+ T cells. The stimulated T cells were infused to patients after T-cell depleted transplantation, with promising results and no GvHD.
20. Yong AS, Keyvanfar K, Eniafe R, et al. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy. Leukemia. 2008;22:1721-7.
21. Mohty M, Yong AS, Szydlo RM, Apperley JF, Melo JV. The polycomb group BMI-1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood. 2007;110:380-3.
22. Kaeda J, O'Shea D, Szydlo RM, 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;107:4171-6.
23. de Lavallade H, Apperley JF, Khorashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358-63.
24. Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002;99:319-25.
25. Copland M, Hamilton A, Elrick LJ, et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood. 2006;107:4532-9.
26. • Warlick E, Ahn KW, Pedersen TL, 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;119:4083-90. CIBMTR data analysis of 306 CML patients >39 years old transplanted between 2001 and 2007. Their survival was similar across the ages, but the relapse incidence was higher in patients >69 years old with no significant difference apparent in those transplanted in the first chronic phase. Nonmyeloablative conditioning/reduced intensity conditioning was inferior to more intensive conditioning.
27. Or R, Shapira MY, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood. 2003;101:441-5.
28. Crawley C, Szydlo R, Lalancette 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;106:2969-76.
29. Martin PJ, Hansen JA, Buckner CD, et al. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood. 1985;66:664-72.
30. Soiffer RJ, Martin P. T-cell depletion of allogenetic hematopoietic stem cell grafts. In: Atkinson K, Champlin RE, Ritz J, Fibbe WE, Ljungman P, Brenner MK, editors. Clinical bone marrow and blood stem cell transplantation. Cambridge, UK: Cambridge University Press; 2004. p. 416-25.
31. Lee SJ, Zahrieh D, Alyea EP, et al. Comparison of T-cell depleted and non-T-cell depleted unrelated donor transplantations for hematologic diseases: clinical outcomes, quality of life, and costs. Blood. 2002;100:2697-702.
32. Sehn LH, Alyea EP, Weller E, et al. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion. J Clin Oncol. 1999;17:561-8.
33. Olavarria E, Kanfer E, Szydlo R, et al. Early detection of BCR/ABL transcripts by quantitative RT-PCR predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. 2001;97:1560-5.
34. Oehler VG, Radich JP, Storer B, et al. Randomized trial of allogeneic related bone marrow transplantation versus peripheral blood stem cell transplantation for chronic myeloid leukemia. Biol Blood Marrow Transplant. 2005;11:85-92.
35. Gratwohl A, Brand R, Apperley J, 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;91:513-21.
36. Lee SJ, Kukreja M, Wang T, et al. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia. Blood. 2008;112:3500-7.
37. Weisdorf DJ, Nelson G, Lee SJ, et al. Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for CML: refined HLA-matching shows more GVHD but not less relapse. Biol Blood Marrow Transplant. 2009;15:1475-8.
38. Laporte JP, Gorin NC, Rubinstein P, et al. Cord blood transplantation from an unrelated donor in an adult with chronic myelogenous leukemia. N Engl J Med. 1996;335:167-70.
39. • Sanz J, Montesinos P, Saavedra S, et al. Single-unit umbilical cord blood transplantation from unrelated donors in adult patients with chronic myeloid leukemia. Biol Blood Marrow Transplant. 2010;16:1589-95. A retrospective single-center study of 26 adults with CML receiving unrelated cord blood SCT.
40. Nagamura-Inoue T, Kai S, Azuma H, et al. Unrelated cord blood transplantation in CML: Japan Cord Blood Bank Network analysis. Bone Marrow Transplant. 2008;42:241-51.
41. Huang XJ, Xu LP, Liu KY, 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;40:444-55.
42. Cross NC. Standardisation of molecular monitoring for chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009;22:355-65.
43. • Goldman JM, Majhail NS, Klein JP, et al. Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase. J Clin Oncol. 2010;28:1888-95. This CIBMTR study of 2,444 patients who had survived in continuous complete remission for at least 5 years after SCT for CML in the first chronic phase showed a survival rate of 88 % at 15 years for sibling transplant recipients and 87 % for unrelated recipients. The corresponding incidences of relapse were only 8 % and 2 %, respectively, with the last relapse 18 years after SCT.
44. Dazzi F, Szydlo RM, Cross NC, et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. 2000;96:2712-6.
45. Chalandon Y, Passweg JR, Schmid C, et al. Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the Chronic Leukemia Working Party of the EBMT. Bone Marrow Transplant. 2010;45:558-64.
46. Olavarria E, Ottmann OG, Deininger M, et al. Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2003;17:1707-12.
47. Hess G, Bunjes D, Siegert W, 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;23:7583-93.
48. Atallah E, Kantarjian H, De Lima M, et al. The role of dasatinib in patients with Philadelphia (Ph) positive acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML) relapsing after stem cell transplantation (SCT) (American Society of Hematology Annual Meeting Abstracts). Blood. 2006;108:abstract 4520.
49. Klyuchnikov E, Schafhausen P, Kroger N, et al. Second-generation tyrosine kinase inhibitors in the post-transplant period in patients with chronic myeloid leukemia or Philadelphia-positive acute lymphoblastic leukemia. Acta Haematol. 2009;122:6-10.
50. Kantarjian HM, O'Brien S, Cortes JE, et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood. 2002;100:1590-5.
51. Weisser M, Tischer J, Schnittger S, et al. 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;91:663-6.
52. Savani BN, Montero A, Kurlander R, et al. Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36:1009-15.
53. Garland P, Dazzi F, Marin D. Dasatinib may not suppress the GVL effect of donor lymphocyte infusions for CML. Bone Marrow Transplant. 2010;45:395-6.
54. Olavarria E, Siddique S, Griffiths MJ, et al. Post-transplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110:4614-7.
55. Carpenter PA, Snyder DS, Flowers ME, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007;109:2791-3.
56. • Sauselle S, Lauseker M, Gratwohl A, et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in the imatinib era; evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood. 2010;115:1880-5. A multicenter study of 84 patients who underwent SCT after pretreatment with imatinib. Patients with EBMT score 0 or 1 had SCT early (n = 19), 37 patients after imatinib failure, and 28 patients for advanced phase disease. With a median follow up of 24 months the estimated 3-year survival of patients in chronic and advanced phase was 91 % and 59 %, respectively.
57. Jabbour E, Cortes J, Santos FP, et al. Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. Blood. 2011;117:3641-7.
58. Nicolini FE, Basak GW, Soverini S, et al. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias. Blood. 2011;118:5697-700.
59. Marin D. Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia. American Society of Hematology Education Program. 2012. In press.
60. Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30:232-8.
61. Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011;12:841-51.
62. Kantarjian HM, Shah NP, Cortes JE, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119:1123-9.
63. Milojkovic D, Apperley JF, Gerrard G, et al. Responses to second line tyrosine kinase inhibitors are durable: an intention to treat analysis in chronic myeloid leukemia patients. Blood. 2012;119:1838-43.
64. Cortes JE, Kantarjian HM, Brummendorf TH, et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011;118:4567-76.
65. Garg RJ, Kantarjian H, O'Brien S, et al. The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood. 2009;114:4361-8.
66. Ibrahim AR, Paliompeis C, Bua M, et al. Efficacy of tyrosine kinase inhibitors (TKIs) as third-line therapy in patients with chronic myeloid leukemia in chronic phase who have failed 2 prior lines of TKI therapy. Blood. 2010;116:5497-500.
67. Cortes JE, Feldman EJ, Yee K, et al. Subset analysis of response to treatment of chronic phase CML in a phase 1 study of ponatinib in refractory hematologic malignancies (American Society of Hematology Annual Meeting Abstracts). Blood 2011;118:abstract 601.
68. Cortes JE, Talpaz M, Kantarjian HM, et al. A phase 1 study of DCC-2036, a novel oral inhibitor of BCR-ABL kinase, in patients with Philadelphia chromosome positive (Ph+) leukemias including patients with T315I mutation (American Society of Hematology Annual Meeting Abstracts). Blood. 2011;118:abstract 601.
69. Carella AM, Goldman JM, Martinelli G, et al. Chronic myeloid leukemia: the basis of treatment for tomorrow. Haematologica. 2011;96:1737-9.
70. Gratwohl A, Hermans J, Goldman JM, 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;352:1087-92.
71. Passweg JR, Walker I, Sobocinski KA, et al. Validation and extension of the EBMT Risk Score for patients with chronic myeloid leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants. Br J Haematol. 2004;125:613-20.
72. Pavlu J, Kew A, Taylor-Roberts B, et al. Optimizing patient selection for allogeneic hematopoietic cell transplantation in chronic myeloid leukemia in chronic phase. Blood. 2010;115:4018-20.
73. Ibrahim AR, Clark RE, Holyoake TL, et al. Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed. Haematologica. 2011;96:1779-82.
74. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041-51.
75. Jabbour E, Kantarjian HM, O'Brien S, et al. Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: what is the optimal response? J Clin Oncol. 2011;29:4260-5.
76. Wang L, Pearson K, Ferguson JE, et al. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol. 2003:990-999.
77. Hanfstein B, Müller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096-102.
78. Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116:3758-65.
79. Marin D, Hedgley C, Clark RE, et al. Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first line dasatinib. Blood. 2012;120:291-4.
80. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928-37.
81. Palandri F, Castagnetti F, Alimena G, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up. Haematologica. 2009;94:205-12.
82. Rea D, Etienne G, Nicolini F, et al. First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia. 2012;26:2254-9.
83. Kantarjian H, Cortes J, Kim DW, 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;113:6322-9.
84. Le Coutre PD, Giles FJ, Hochhaus A, 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;26:1189-94.
85. • Khoury HJ, Kukreja M, Goldman JM, et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis. Bone Marrow Transplant. 2012;47:810-6. A CIBMTR study of 449 allogeneic hematopoietic SCTs performed from 1999 to 2004 in advanced-phase CML. Estimated 3-year survival was 35-50 % for second chronic phase, 29-43 % for accelerated phase and 8-23 % for blast phase.
86. Jiang Q, Xu LP, Liu DH, et al. Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase. Blood. 2011;117:3032-40.
87. Visani G, Rosti G, Bandini G, et al. Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia. Br J Haematol. 2000;109:722-8.
88. Fruehauf S, Topaly J, Buss EC, et al. Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis. Cancer. 2007;109:1543-9.
89. Milojkovic D, Ibrahim A, Reid A, et al. Efficacy of combining dasatinib and FLAG-IDA for patients with chronic myeloid leukemia in blastic transformation. Haematologica. 2012;97:473-4.