Advertisement

International Journal of Hematology

, Volume 79, Issue 4, pp 345–353 | Cite as

Multicenter Prospective Study of Interferon α versus Allogeneic Stem Cell Transplantation for Patients with New Diagnoses of Chronic Myelogenous Leukemia

  • Kazunori Ohnishi
  • Akio Ino
  • Yuji Kishimoto
  • Noriko Usui
  • Chihiro Shimazaki
  • Shigeki Ohtake
  • Hirokuni Taguchi
  • Fumiharu Yagasaki
  • Masao Tomonaga
  • Tomomitsu Hotta
  • Ryuzo Ohno
  • Japan Adult Leukemia Study Group
Article

Abstract

We compared interferon α (IFN-α) therapy with stem cell transplantation (SCT) for patients with chronic-phase chronic myelogenous leukemia in a multicenter prospective study to investigate the optimal indication and timing of SCT, especially from HLA-matched unrelated donors. Of 257 eligible patients, 145 patients who were younger than 50 years were assigned to the IFN-α cohort (n = 87) or the SCT cohort (n = 58), according to family donor availability. In the IFN-α cohort, 52 patients received IFN-α and chemotherapy (the IFN1 group), and 35 patients received an SCT from an unrelated donor (the U-SCT group). In the SCT cohort, 47 patients received an SCT from a related donor (the R-SCT group). In the IFN1 group, 88% of the patients achieved a complete hematologic response, and 33% achieved a complete cytogenetic response. At a median follow-up period of 53 months, the predicted 6-year survival rate was 72% in the IFN1 group, 81% in the R-SCT group, and 81% in the U-SCT group. When overall survival was evaluated for the IFN-α and R-SCT cohorts by intention to treat according to family donor availability, the 6-year survival rates were 76% and 84%, respectively. When the outcomes of the U-SCT and IFN1 groups were compared, the survival rate of U-SCT group patients was significantly better than for IFN1 group patients without a major cytogenetic response and seemed better for IFN1 group patients younger than 35 years. Therefore, U-SCT may be recommendable to patients who fail to achieve a major cytogenetic response in IFN-α therapy and to younger patients.

Key words

Interferon α Chronic myelogenous leukemia SCT Unrelated donor Prospective multicenter study 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Silver RT, Woolf SH, Hehlmann R, et al An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology.Blood. 1999;94:1517–1536.Google Scholar
  2. 2.
    Ohnishi K, Ohno R, Tomonaga M, et al A randomize1d trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase.Blood. 1995;86:906–916.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Ohnishi K, Tomonaga M, Kamada N, et al A long term follow-up of a randomized trial comparing interferon-alpha with busulfan for chronic myelogenous leukemia: the Kouseisho Leukemia Study Group.Leuk Res. 1998;22:779–786.CrossRefGoogle Scholar
  4. 4.
    Ohnishi K, Minami S, Ueda T, et al Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia: Kouseisho Leukemia Study Group.Int J Hematol. 2000;72:229–236.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Druker BJ, Talpaz M, Resta DJ, et al Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.N Engl J Med. 2001;344:1031–1037.CrossRefPubMedGoogle Scholar
  6. 6.
    Kantarjian H, Sawyers C, Hochhaus A, et al, and the International STI571 CML Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.N Engl J Med. 2002;346:645–652.CrossRefGoogle Scholar
  7. 7.
    Kitajima K, Ishibashi M, Nagao T, Takahashi I, Kinoshita H. Clinical studies on the early diagnosis and treatment of blastic crisis of chronic myelogenous leukemia [in Japanese].Rinsho Ketsueki. 1972;13:560–568.Google Scholar
  8. 8.
    Talpaz M, Kantarjian H, McCredie KB, Keating MJ, Trujillo J, Gutterman J. Clinical investigation of human alpha interferon in chronic myelogenous leukemia.Blood. 1987;69:1280–1288.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia.Blood. 1984;63:789–799.Google Scholar
  10. 10.
    Hansen JA, Gooley TA, Martin PJ, et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.N Engl J Med. 1998;338:962–968.CrossRefPubMedGoogle Scholar
  11. 11.
    Japan Society for Hematopoietic Cell Transplantation. Annual report of nationwide survey 1999.JSHCT Monogr. 1999;2:68–79.Google Scholar
  12. 12.
    Sasazuki T, Juji T, Morishima Y, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor: Japan Marrow Donor Program.N Engl J Med. 1998;339:1177–1185.CrossRefPubMedGoogle Scholar
  13. 13.
    Italian Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia.N Engl J Med. 1994;330:820–825.CrossRefGoogle Scholar
  14. 14.
    Italian Cooperative Study Group on Chronic Myeloid Leukemia and Italian Group for Bone Marrow Transplantation. Monitoring treatment and survival in chronic myeloid leukemia. JClin Oncol. 1999;17:1858–1868.CrossRefGoogle Scholar
  15. 15.
    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; 91:1810–1819.Google Scholar
  16. 16.
    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;84:4064–4077.Google Scholar
  17. 17.
    Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation.Blood. 2002;99:1971–1977.CrossRefGoogle Scholar
  18. 18.
    O’Brien SG, Guilhot F, Larson RA, et al, and the IRIS investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.N Engl J Med. 2003;348:994–1004.CrossRefGoogle Scholar
  19. 19.
    Hughes T, Kaeda J, Branford S, et al. Molecular responses to imatinib (STI571) or interferon + Ara-C as initial therapy for CML: results in the IRIS Study [abstract].Blood. 2002;100:93a-94a.Google Scholar
  20. 20.
    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; 99:319–325.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Kazunori Ohnishi
    • 1
  • Akio Ino
    • 2
  • Yuji Kishimoto
    • 3
  • Noriko Usui
    • 4
  • Chihiro Shimazaki
    • 5
  • Shigeki Ohtake
    • 6
  • Hirokuni Taguchi
    • 7
  • Fumiharu Yagasaki
    • 8
  • Masao Tomonaga
    • 9
  • Tomomitsu Hotta
    • 10
  • Ryuzo Ohno
    • 11
  • Japan Adult Leukemia Study Group
  1. 1.Department of Medicine IIIHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Fujita Health University School of MedicineToyoakeJapan
  3. 3.Kansai Medical UniversityMoriguchiJapan
  4. 4.Jikei University School of MedicineTokyoJapan
  5. 5.Kyoto Prefecture University of MedicineKyotoJapan
  6. 6.Kanazawa University School of MedicineKanazawaJapan
  7. 7.Kochi Medical SchoolKochiJapan
  8. 8.Saitama Medical SchoolKawagoeJapan
  9. 9.Department of Hematology, Molecular Medicine, Atomic Bomb Disease InstituteNagasaki University School of MedicineNagasakiJapan
  10. 10.Tokai University School of MedicineIseharaJapan
  11. 11.Aichi Cancer Center HospitalNagoyaJapan

Personalised recommendations