Seminars in Hematology
Volume 46 , Pages S26-S32 , January 2009

Management of Chemotherapy-Induced Thrombocytopenia: Current Status of Thrombopoietic Agents

  • Saroj Vadhan-Raj

      Affiliations

    • Corresponding Author InformationAddress correspondence to Saroj Vadhan-Raj, MD, Chief, Section of Cytokines and Supportive Oncology, Professor of Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

References 

  1. Kaushansky K. The thrombocytopenia of cancer (Prospects for effective cytokine therapy). Hematol Oncol Clin North Am. 1996;10:431–455
  2. Elting LS, Rubenstein EB, Martin CG, Kurtin D, Rodriguez S, Laiho E, et al. Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia. J Clin Oncol. 2001;19:1137–1146
  3. Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10:64–71
  4. Debili N, Masse JM, Katz A, Guichard J, Breton-Gorius J, Vainchenker W. Effects of the recombinant hematopoietic growth factors interleukin-3, interleukin-6, stem cell factor, and leukemia inhibitory factor on the megakaryocytic differentiation of CD34+ cells. Blood. 1993;82:84–95
  5. Norol F, Vitrat N, Cramer E, Guichard J, Burstein SA, Vainchenker W, et al. Effects of cytokines on platelet production from blood and marrow CD34+ cells. Blood. 1998;91:830–843
  6. Guerriero R, Mattia G, Testa U, Chelucci C, Macioce G, Casella I, et al. Stromal cell-derived factor 1alpha increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells. Blood. 2001;97:2587–2595
  7. Kuter DJ, Begley CG. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood. 2002;100:3457–3469
  8. Elting LS, Cantor SB, Martin CG, Hamblin L, Kurtin D, Rivera E, et al. Cost of chemotherapy-induced thrombocytopenia among patients with lymphoma or solid tumors. Cancer. 2003;97:1541–1550
  9. Lonial S, Waller EK, Richardson PG, Jagannath S, Orlowski RZ, Giver CR, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood. 2005;106:3777–3784
  10. Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995;332:901–906
  11. Chang J. Chemotherapy dose reduction and delay in clinical practice (Evaluating the risk to patient outcome in adjuvant chemotherapy for breast cancer). Eur J Cancer. 2000;36(Suppl 1):S11–S14
  12. Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1519–1538
  13. Wallace EL, Churchill WH, Surgenor DM, Cho GS, McGurk S. Collection and transfusion of blood and blood components in the United States, 1994. Transfusion. 1998;38:625–636
  14. Cobain TJ, Vamvakas EC, Wells A, Titlestad K. A survey of the demographics of blood use. Transfus Med. 2007;17:1–15
  15. Brecher ME. The platelet prophylactic transfusion trigger: when expectations meet reality. Transfusion. 200; 47:188-91.
  16. Demetri GD. Targeted approaches for the treatment of thrombocytopenia. Oncologist. 2001;6(Suppl 5):15–23
  17. Gaydos LA, Freireich EJ, Mantel N. The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med. 1962;266:905–909
  18. Slichter SJ, Harker LA. Thrombocytopenia: mechanisms and management of defects in platelet production. Clin Haematol. 1978;7:523–539
  19. Benjamin RJ, Anderson KC. What is the proper threshold for platelet transfusion in patients with chemotherapy-induced thrombocytopenia?. Crit Rev Oncol Hematol. 2002;42:163–171
  20. Ciurea SO, Hoffman R. Cytokines for the treatment of thrombocytopenia. Semin Hematol. 2007;44:166–182
  21. Tepler I, Elias L, Smith JW, Hussein M, Rosen G, Chang AY, et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood. 1996;87:3607–3614
  22. Cairo MS, Davenport V, Bessmertny O, Goldman SC, Berg SL, Kreissman SG, et al. Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study. Br J Haematol. 2005;128:49–58
  23. Harker LA. Therapeutic cytokine stimulation of thrombocytopoiesis. Transfus Sci. 1998;19:149–162
  24. Vadhan-Raj S, Murray LJ, Bueso-Ramos C, et al. Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann Intern Med. 1997;126:673–681
  25. Basser RL, Rasko JE, Clarke K, Cebon J, Green MD, Hussein S, et al. Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer. Lancet. 1996;348:1279–1281
  26. Fanucchi M, Glaspy J, Crawford J, Garst J, Figlin R, Sheridan W, et al. Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer. N Engl J Med. 1997;336:404–409
  27. Vadhan-Raj S, Verschraegen CF, Bueso-Ramos C, Broxmeyer HE, Kudelka AP, Freedman RS, et al. Recombinant human thrombopoietin attenuates carboplatin-induced severe thrombocytopenia and the need for platelet transfusions in patients with gynecologic cancer. Ann Intern Med. 2000;132:364–368
  28. Vadhan-Raj S, Patel S, Bueso-Ramos C, Folloder J, Papadopolous N, Burgess A, et al. Importance of predosing of recombinant human thrombopoietin to reduce chemotherapy-induced early thrombocytopenia. J Clin Oncol. 2003;21:3158–3167
  29. Vadhan-Raj S, Cohen V, Bueso-Ramos C. Thrombopoietic growth factors and cytokines. Curr Hematol Rep. 2005;4:137–144
  30. Schiffer CA, Miller K, Larson RA, Amrein PC, Antin JH, Zani VJ, et al. A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia. Blood. 2000;95:2530–2535
  31. Vadhan-Raj S, Kavanagh JJ, Freedman RS, Folloder J, Currie LM, Bueso-Ramos C, et al. Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study. Lancet. 2002;359:2145–2152
  32. Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76:628–638
  33. Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007;109:4739–4741
  34. Desjardins RE, Tempel DL, Lucek R, Kuter DJ. Single and multiple oral doses of AKR-501 (YM477) increases the platelet count in healthy volunteers [abstract 477]. Blood. 2006;108:145a
  35. SB-497115 (oral thrombopoietin receptor agonist) versus placebo in adult cancer patients receiving chemotherapy. http://clinicaltrials.gov/ct2/show/NCT00102726Accessed September 11, 2008.
  36. Dose evaluation study of oral eltrombopag in patients with sarcoma receiving the adriamycin and ifosfamide regimen. http://clinicaltrials.gov/ct2/show/NCT00358540Accessed September 11, 2008.

 STATEMENT OF CONFLICT OF INTEREST: Saroj Vadhan-Raj, MD, discloses the following: Investigator: Amgen, GSK.

PII: S0037-1963(08)00206-0

doi: 10.1053/j.seminhematol.2008.12.007

Seminars in Hematology
Volume 46 , Pages S26-S32 , January 2009

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