The Evolving Role of Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia

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• 作者：Matthew S. Davids (1)
  Edwin P. Alyea (1)
  
  1. Department of Medical Oncology ; Dana-Farber Cancer Institute ; 450 Brookline Avenue ; Boston ; MA ; 02215 ; USA
  
• 关键词：Allogeneic transplantation ; Stem cell transplantation ; Kinase inhibitor ; Novel agent ; Chemoimmunotherapy ; Graft versus host disease
• 刊名：Current Hematologic Malignancy Reports
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：10
• 期：1
• 页码：18-27
• 全文大小：459 KB
• 参考文献：1. Rai, KR, Peterson, BL, Appelbaum, FR, Kolitz, J, Elias, L, Shepherd, L (2000) Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 343: pp. 1750-7 CrossRef
  2. Eichhorst, BF, Busch, R, Hopfinger, G, Pasold, R, Hensel, M, Steinbrecher, C (2006) Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood 107: pp. 885-91 CrossRef
  3. Tam, CS, O鈥橞rien, S, Wierda, W, Kantarjian, H, Wen, S, Do, KA (2008) Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 112: pp. 975-80 CrossRef
  4. Hallek, M, Fischer, K, Fingerle-Rowson, G, Fink, AM, Busch, R, Mayer, J (2010) Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376: pp. 1164-74 CrossRef
  5. Dohner, H, Stilgenbauer, S, Benner, A, Leupolt, E, Krober, A, Bullinger, L (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343: pp. 1910-6 CrossRef
  6. Hamblin, TJ, Davis, Z, Gardiner, A, Oscier, DG, Stevenson, FK (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94: pp. 1848-54
  7. Rabinowe, SN, Soiffer, RJ, Gribben, JG, Daley, H, Freedman, AS, Daley, J (1993) Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood 82: pp. 1366-76
  8. Pavletic, ZS, Bierman, PJ, Vose, JM, Bishop, MR, Wu, CD, Pierson, JL (1998) High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Ann Oncol 9: pp. 1023-6 CrossRef
  9. Gribben, JG, Zahrieh, D, Stephans, K, Bartlett-Pandite, L, Alyea, EP, Fisher, DC (2005) Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia. Blood 106: pp. 4389-96 CrossRef
  10. Sutton, L, Chevret, S, Tournilhac, O, Divine, M, Leblond, V, Corront, B (2011) Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC. Blood 117: pp. 6109-19 CrossRef
  11. Michallet, M, Dreger, P, Sutton, L, Brand, R, Richards, S, Os, M (2011) Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation. Blood 117: pp. 1516-21 CrossRef
  12. Toze, CL, Galal, A, Barnett, MJ, Shepherd, JD, Conneally, EA, Hogge, DE (2005) Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease. Bone Marrow Transplant 36: pp. 825-30 CrossRef
  13. Doney, KC, Chauncey, T, Appelbaum, FR (2002) Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transplant 29: pp. 817-23 CrossRef
  14. Michallet, M, Archimbaud, E, Bandini, G, Rowlings, PA, Deeg, HJ, Gahrton, G (1996) HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry. Ann Intern Med 124: pp. 311-5 CrossRef
  15. Sabloff, M, Sobecks, RM, Ahn, KW, Zhu, X, Lima, M, Brown, JR (2014) Does total body irradiation conditioning improve outcomes of myeloablative human leukocyte antigen-identical sibling transplantations for chronic lymphocytic leukemia?. Biol Blood Marrow Transplant 20: pp. 421-4 CrossRef
  16. Delgado, J, Thomson, K, Russell, N, Ewing, J, Stewart, W, Cook, G (2006) Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood 107: pp. 1724-30 CrossRef
  17. Sorror, ML, Storer, BE, Sandmaier, BM, Maris, M, Shizuru, J, Maziarz, R (2008) Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol Off J Am Soc Clin Oncol 26: pp. 4912-20 CrossRef
  18. Khouri, IF, Bassett, R, Poindexter, N, O鈥橞rien, S, Bueso-Ramos, CE, Hsu, Y (2011) Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome. Cancer 117: pp. 4679-88 CrossRef
  19. Brown, JR, Kim, HT, Armand, P, Cutler, C, Fisher, DC, Ho, V (2013) Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia 27: pp. 362-9 CrossRef
  20. Dreger, P, Dohner, H, Ritgen, M, Bottcher, S, Busch, R, Dietrich, S (2010) Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood 116: pp. 2438-47 CrossRef
  21. Sobecks, RM, Leis, JF, Gale, RP, Ahn, KW, Zhu, X, Sabloff, M (2014) Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens. Biol Blood Marrow Transplant 20: pp. 1390-8 CrossRef
  22. Brown, JR, Kim, HT, Li, S, Stephans, K, Fisher, DC, Cutler, C (2006) Predictors of improved progression-free survival after nonmyeloablative allogeneic stem cell transplantation for advanced chronic lymphocytic leukemia. Biol Blood Marrow Transplant 12: pp. 1056-64 CrossRef
  23. Dreger, P, Schnaiter, A, Zenz, T, Bottcher, S, Rossi, M, Paschka, P (2013) TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood 121: pp. 3284-8 CrossRef
  24. Pidala, J, Anasetti, C, Jim, H (2009) Quality of life after allogeneic hematopoietic cell transplantation. Blood 114: pp. 7-19 CrossRef
  25. Dreger, P, Corradini, P, Kimby, E, Michallet, M, Milligan, D, Schetelig, J (2007) Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia 21: pp. 12-7 CrossRef
  26. Landau, DA, Carter, SL, Stojanov, P, McKenna, A, Stevenson, K, Lawrence, MS (2013) Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152: pp. 714-26 CrossRef
  27. Stilgenbauer, S, Sander, S, Bullinger, L, Benner, A, Leupolt, E, Winkler, D (2007) Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica 92: pp. 1242-5 CrossRef
  28. Byrd, JC, Furman, RR, Coutre, SE, Flinn, IW, Burger, JA, Blum, KA (2013) Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 369: pp. 32-42 CrossRef
  29. Byrd, JC, Brown, JR, O鈥橞rien, S, Barrientos, JC, Kay, NE, Reddy, NM (2014) Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 371: pp. 213-23 CrossRef
  30. Brown, JR, Byrd, JC, Coutre, SE, Benson, DM, Flinn, IW, Wagner-Johnston, ND (2014) Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood 123: pp. 3390-7 CrossRef
  31. Furman, RR, Sharman, JP, Coutre, SE, Cheson, BD, Pagel, JM, Hillmen, P (2014) Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 370: pp. 997-1007 CrossRef
  32. Seymour JF, Davids MS, Pagel JM, al. e, editors. ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): high complete response rate and durable disease control. American Society of Clinical Oncology Annual Meeting; 2014. / Report on the important phase I study of ABT-199 in relapsed/refractory CLL that identified the recommended dose of the drug and defined its preliminary efficacy and toxicity.
  33. Roberts, AW, Ma, S, Brander, DM (2014) Determination of recommended phase 2 dose of ABT-199 (GDC-0199) combined with rituximab (R) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Blood 124: pp. 325
  34. Herman, SE, Gordon, AL, Hertlein, E, Ramanunni, A, Zhang, X, Jaglowski, S (2011) Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 117: pp. 6287-96 CrossRef
  35. Cuni, S, Perez-Aciego, P, Perez-Chacon, G, Vargas, JA, Sanchez, A, Martin-Saavedra, FM (2004) A sustained activation of PI3K/NF-kappaB pathway is critical for the survival of chronic lymphocytic leukemia B cells. Leukemia 18: pp. 1391-400 CrossRef
  36. Hoellenriegel, J, Meadows, SA, Sivina, M, Wierda, WG, Kantarjian, H, Keating, MJ (2011) The phosphoinositide 3鈥?kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 118: pp. 3603-12 CrossRef
  37. Peluso, M, Faia, K, Winkler, D (2014) Duvelisib (IPI-145) inhibits malignant B-cell proliferation and disrupts signaling from the tumor microenvironment through mechanisms that are dependent on PI3K-未 and PI3K-纬. Blood 124: pp. 328
  38. O鈥橞rien, S, Patel, M, Kahl, BS (2014) Duvelisib (IPI-145), a PI3K-未, 纬 inhibitor, is clinically active in patients with relapsed/refractory chronic lymphocytic leukemia. Blood 124: pp. 1982
  39. Burris, HA, Patel, MR, Brander, DM (2014) TGR-1202, a novel once daily pi3k未 inhibitor, demonstrates clinical activity with a favorable safety profile, lacking hepatotoxicity, in patients with chronic lymphocytic leukemia and B-cell lymphoma. Blood 124: pp. 1984
  40. Lunning, MA, Vose, JM, Schreeder, MD (2014) Ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody (mAb), in combination with TGR-1202, a next generation once daily PI3k未 inhibitor, demonstrates activity in heavily pre-treated and high-risk chronic lymphocytic leukemia (CLL) and B-cell lymphoma. Blood 124: pp. 801
  41. Gaizo Moore, V, Brown, JR, Certo, M, Love, TM, Novina, CD, Letai, A (2007) Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest 117: pp. 112-21 CrossRef
  42. Souers, AJ, Leverson, JD, Boghaert, ER, Ackler, SL, Catron, ND, Chen, J (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19: pp. 202-8 CrossRef
  43. Porter, DL, Levine, BL, Kalos, M, Bagg, A, June, CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365: pp. 725-33 CrossRef
  44. Porter, DL, Frey, NV, Melenhorst, JJ (2014) Randomized, phase II dose optimization study of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed refractory CLL. Blood 124: pp. 3334
  45. Dreger, P, Schetelig, J, Andersen, N, Corradini, P, Gelder, M, Gribben, J (2014) Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: stem cell transplantation or novel agents?. Blood.
  46. Zenz, T, Eichhorst, B, Busch, R, Denzel, T, Habe, S, Winkler, D (2010) TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol Off J Am Soc Clin Oncol 28: pp. 4473-9 CrossRef
  47. Puente, XS, Pinyol, M, Quesada, V, Conde, L, Ordonez, GR, Villamor, N (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475: pp. 101-5 CrossRef
  48. Quesada, V, Conde, L, Villamor, N, Ordonez, GR, Jares, P, Bassaganyas, L (2012) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 44: pp. 47-52 CrossRef
  49. Wang, L, Lawrence, MS, Wan, Y, Stojanov, P, Sougnez, C, Stevenson, K (2011) SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 365: pp. 2497-506 CrossRef
  50. Rossi, D, Rasi, S, Fabbri, G, Spina, V, Fangazio, M, Forconi, F (2012) Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 119: pp. 521-9 CrossRef
  51. Dubovsky, JA, Beckwith, KA, Natarajan, G, Woyach, JA, Jaglowski, S, Zhong, Y (2013) Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood 122: pp. 2539-49 CrossRef
  
• 刊物主题：Hematology; Oncology; Geriatrics/Gerontology;
• 出版者：Springer US
• ISSN：1558-822X

文摘

Chronic lymphocytic leukemia (CLL) patients with high-risk markers such as del(17p) or those who have relapsed after multiple lines of therapy have a poor prognosis and allogeneic hematopoietic cell transplantation (alloHCT) has historically been the best opportunity for achieving long-term disease control. Recently, several new highly efficacious and well-tolerated small molecules targeting the B cell receptor (BCR) pathway and Bcl-2 have been approved or are in the late stages of development. These new agents are altering therapeutic paradigms in CLL, but unlike with alloHCT, information on long-term disease control is lacking. Here, we provide an overview of the data supporting the use of HCT in CLL and the promising results with the novel agents. We discuss the evolving role of alloHCT for CLL in the novel agent era, including identifying the patients most likely to benefit from transplantation and optimal transplantation timing, as well the use of novel agents in the post-transplantation setting.