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Interferon alfa for the treatment of chronic myeloid leukemia

Robert S Negrin, MD
Charles A Schiffer, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Interferon alfa (IFNa) has been extensively studied as treatment for patients with chronic myeloid leukemia (CML) since 1981, initially using partially purified IFNa [1], followed by recombinant IFNa-2a [2]. Prior to the development of the tyrosine kinase inhibitor (TKI) imatinib mesylate, interferon was the non-transplant treatment of choice for most patients with CML. However, with the development of TKIs and the increased toxicity of interferon compared with TKIs, this latter drug has been used much less commonly for the treatment of CML.

The use of interferon alfa in the treatment of CML will be discussed here. Other treatment options are discussed separately. (See "Overview of the treatment of chronic myeloid leukemia" and "Initial treatment of chronic myeloid leukemia in chronic phase" and "Treatment of chronic myeloid leukemia in accelerated phase" and "Treatment of chronic myeloid leukemia in blast crisis" and "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia" and "Hematopoietic cell transplantation in chronic myeloid leukemia".)


Hematologic remissions have been noted in the majority of patients using IFNa-2a as a single agent and complete cytogenetic remissions (ie, absence of any Ph+ metaphase by conventional cytogenetics) were noted in a minority of patients, ranging from 13 to 27 percent [3,4].

The rate of cytogenetic response was higher in younger patients and in those with lower Sokal risk categories [5,6]. Although the degree of cytogenetic response can improve over time, it is uncommon to observe cytogenetic responses with further treatment if no reductions in the percent of Philadelphia chromosome metaphases have been seen during the first year of treatment.

In occasional patients, cytogenetic remissions were sustained for long periods of time, and in those patients with major cytogenetic responses, survival appeared to be improved [7]. Because of the considerable side effects from interferon, many clinicians chose to stop interferon therapy if cytogenetic improvement had not been seen after approximately one year of treatment. In two studies, 10-year survival ranged from 72 to 78 percent in patients achieving complete cytogenetic response to IFNa [3,4]. The majority of patients who achieve complete cytogenetic remission following treatment with IFNa still have molecular evidence of disease when assessed by the more sensitive polymerase chain reaction (PCR) [4,8-10], although there have been occasional patients in long term cytogenetic response who have not relapsed after cessation of the interferon. In part because of this observation, there are ongoing or planned clinical trials that administer IFNa late in the treatment course as a means of increasing the depth of response so as to permit discontinuation of tyrosine kinase inhibitors in a higher fraction of patients.

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Literature review current through: Nov 2017. | This topic last updated: Jan 13, 2017.
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  1. Talpaz M, McCredie KB, Mavligit GM, Gutterman JU. Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood 1983; 62:689.
  2. Talpaz M, Kantarjian HM, McCredie K, et al. Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. N Engl J Med 1986; 314:1065.
  3. Bonifazi F, de Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood 2001; 98:3074.
  4. Kantarjian HM, O'Brien S, Cortes JE, et al. Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 2003; 97:1033.
  5. Sokal JE, Baccarani M, Russo D, Tura S. Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 1988; 25:49.
  6. Sokal risk score calculator available online at www.roc.se/sokal.asp (Accessed on April 03, 2006).
  7. Talpaz M, Kantarjian H, Kurzrock R, et al. Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med 1991; 114:532.
  8. Lee MS, Kantarjian H, Talpaz M, et al. Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy. Blood 1992; 79:1920.
  9. Talpaz M, Estrov Z, Kantarjian H, et al. Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J Clin Invest 1994; 94:1383.
  10. Chomel JC, Brizard F, Veinstein A, et al. Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation. Blood 2000; 95:404.
  11. Kantarjian HM, Smith TL, O'Brien S, et al. Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service. Ann Intern Med 1995; 122:254.
  12. Schofield JR, Robinson WA, Murphy JR, Rovira DK. Low doses of interferon-alpha are as effective as higher doses in inducing remissions and prolonging survival in chronic myeloid leukemia. Ann Intern Med 1994; 121:736.
  13. Kluin-Nelemans HC, Buck G, le Cessie S, et al. Randomized comparison of low-dose versus high-dose interferon-alfa in chronic myeloid leukemia: prospective collaboration of 3 joint trials by the MRC and HOVON groups. Blood 2004; 103:4408.
  14. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood 1994; 84:4064.
  15. Italian Cooperative Study Group on Chronic Myeloid Leukemia, Tura S, Baccarani M, et al. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 1994; 330:820.
  16. Allan NC, Richards SM, Shepherd PC. UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. Lancet 1995; 345:1392.
  17. Ohnishi K, Ohno R, Tomonaga M, et al. A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood 1995; 86:906.
  18. Sacchi S, Kantarjian H, O'Brien S, et al. Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia. J Clin Oncol 1995; 13:2401.
  19. Zuber J, Martinez F, Droz D, et al. Alpha-interferon-associated thrombotic microangiopathy: a clinicopathologic study of 8 patients and review of the literature. Medicine (Baltimore) 2002; 81:321.
  20. Mahon FX, Delbrel X, Cony-Makhoul P, et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol 2002; 20:214.
  21. Gale RP, Hehlmann R, Zhang MJ, et al. Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia. The German CML Study Group. Blood 1998; 91:1810.
  22. Long-term follow-Up of the italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Blood 1998; 92:1541.
  23. Sokal JE, Leong SS, Gomez GA. Preferential inhibition by cytarabine of CFU-GM from patients with chronic granulocytic leukemia. Cancer 1987; 59:197.
  24. Sokal JE, Gockerman JP, Bigner SH. Evidence for a selective antileukemic effect of cytosine arabinoside in chronic granulocytic leukemia. Leuk Res 1988; 12:453.
  25. Robertson MJ, Tantravahi R, Griffin JD, et al. Hematologic remission and cytogenetic improvement after treatment of stable-phase chronic myelogenous leukemia with continuous infusion of low-dose cytarabine. Am J Hematol 1993; 43:95.
  26. Kantarjian HM, Keating MJ, Estey EH, et al. Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine. J Clin Oncol 1992; 10:772.
  27. Thaler J, Fluckinger T, Huber H, et al. Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside. Leuk Res 1993; 17:711.
  28. Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med 1997; 337:223.
  29. Baccarani M, Rosti G, de Vivo A, et al. A randomized study of interferon-alpha versus interferon-alpha and low-dose arabinosyl cytosine in chronic myeloid leukemia. Blood 2002; 99:1527.
  30. del Cañizo MC, Fisac MP, Galende J, et al. Continuous oral cytarabine ocfosfate with interferon-alpha-2b for patients with newly diagnosed chronic myeloid leukaemia: a pilot study. Br J Haematol 2001; 115:541.
  31. Garcia-Manero G, Talpaz M, Giles FJ, et al. Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside. Cancer 2003; 97:3010.
  32. Talpaz M, Rakhit A, Rittweger K, et al. Phase I evaluation of a 40-kDa branched-chain long-acting pegylated IFN-alpha-2a with and without cytarabine in patients with chronic myelogenous leukemia. Clin Cancer Res 2005; 11:6247.
  33. 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.
  34. Burchert A, Neubauer A. Interferon alpha and T-cell responses in chronic myeloid leukemia. Leuk Lymphoma 2005; 46:167.
  35. Palandri F, Castagnetti F, Iacobucci I, et al. The response to imatinib and interferon-alpha is more rapid than the response to imatinib alone: a retrospective analysis of 495 Philadelphia-positive chronic myeloid leukemia patients in early chronic phase. Haematologica 2010; 95:1415.
  36. Burchert A, Müller MC, Kostrewa P, et al. Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol 2010; 28:1429.
  37. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010; 363:2511.
  38. 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.
  39. Palandri F, Iacobucci I, Castagnetti F, et al. Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-alpha: 5-year outcome. Haematologica 2008; 93:770.
  40. Guilhot F, Preudhomme C, Guilhot J, et al. Significant higher rates of undetectable molecular residual disease and molecular responses with pegylated form of interferon a2a in combination with imatinib for the treatment of newly diagnosed chronic phase chronic myeloid leukemia patients: confirmatory results at 18 months of part 1 of the spirit phase III randomized trial of the French CML Group (abstract 340). Blood 2009; 114:144s.
  41. Pletsch N, Saussele S, Lauseker M, et al. Optimization of imatinib therapy by combination. 5 year survival and response results of the pilot phase of the randomized German CML study IV (abstract 862). Blood 2009; 114:355.
  42. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408.
  43. Branford S, Hughes T, Milner A, et al. Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-alpha. Cancer 2007; 110:801.
  44. Malagola M, Breccia M, Skert C, et al. Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era. Am J Hematol 2014; 89:119.