Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis

Hagop M. Kantarjian, Susan O'Brien, Jorge E. Cortes, Jianqin Shan, Francis J. Giles, Mary Beth Rios, Stefan H. Faderl, William G. Wierda, Alessandra Ferrajoli, Srdan Verstovsek, Michael J. Keating, Emil J. Freireich, Moshe Talpaz

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Little is known regarding long-term prognosis among patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph-positive cells) after treatment with interferon-α. METHODS. The authors analyzed 512 patients with Ph-positive, early chronic-phase CML who were treated with interferon-based therapies between 1981-1995 for the incidence and durability of complete cytogenetic response, and in relation to long-term prognosis. RESULTS. One hundred forty patients (27%) achieved a complete cytogenetic response. Their 10-year survival rate was 78%. At the time of last follow-up, 44 patients (31%, 9% of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88-191 months); 39 patients had not received any therapy for a median of 50 months (range, 11-139 months). Analysis by reverse transcriptase-polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow-up, but only 2 had died of disease-specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response. CONCLUSIONS. Achieving a complete cytogenetic or molecular response after therapy with interferon-α appears to be associated with excellent long-term prognosis. Approximately 10% of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long-term event-free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate.

Original languageEnglish (US)
Pages (from-to)1033-1041
Number of pages9
JournalCancer
Volume97
Issue number4
DOIs
StatePublished - Feb 15 2003
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Interferons
Therapeutics
Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Stem Cell Transplantation
Reverse Transcriptase Polymerase Chain Reaction
Disease-Free Survival
Survival Rate
Recurrence
Incidence

Keywords

  • Chronic myelogenous leukemia (CML)
  • Complete durable cytogenetic response
  • Interferon-α (IFN-α)
  • Molecular response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. / Kantarjian, Hagop M.; O'Brien, Susan; Cortes, Jorge E.; Shan, Jianqin; Giles, Francis J.; Rios, Mary Beth; Faderl, Stefan H.; Wierda, William G.; Ferrajoli, Alessandra; Verstovsek, Srdan; Keating, Michael J.; Freireich, Emil J.; Talpaz, Moshe.

In: Cancer, Vol. 97, No. 4, 15.02.2003, p. 1033-1041.

Research output: Contribution to journalArticle

Kantarjian, HM, O'Brien, S, Cortes, JE, Shan, J, Giles, FJ, Rios, MB, Faderl, SH, Wierda, WG, Ferrajoli, A, Verstovsek, S, Keating, MJ, Freireich, EJ & Talpaz, M 2003, 'Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis', Cancer, vol. 97, no. 4, pp. 1033-1041. https://doi.org/10.1002/cncr.11223
Kantarjian, Hagop M. ; O'Brien, Susan ; Cortes, Jorge E. ; Shan, Jianqin ; Giles, Francis J. ; Rios, Mary Beth ; Faderl, Stefan H. ; Wierda, William G. ; Ferrajoli, Alessandra ; Verstovsek, Srdan ; Keating, Michael J. ; Freireich, Emil J. ; Talpaz, Moshe. / Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. In: Cancer. 2003 ; Vol. 97, No. 4. pp. 1033-1041.
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title = "Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis",
abstract = "BACKGROUND. Little is known regarding long-term prognosis among patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0{\%} Ph-positive cells) after treatment with interferon-α. METHODS. The authors analyzed 512 patients with Ph-positive, early chronic-phase CML who were treated with interferon-based therapies between 1981-1995 for the incidence and durability of complete cytogenetic response, and in relation to long-term prognosis. RESULTS. One hundred forty patients (27{\%}) achieved a complete cytogenetic response. Their 10-year survival rate was 78{\%}. At the time of last follow-up, 44 patients (31{\%}, 9{\%} of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88-191 months); 39 patients had not received any therapy for a median of 50 months (range, 11-139 months). Analysis by reverse transcriptase-polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow-up, but only 2 had died of disease-specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response. CONCLUSIONS. Achieving a complete cytogenetic or molecular response after therapy with interferon-α appears to be associated with excellent long-term prognosis. Approximately 10{\%} of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long-term event-free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate.",
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T1 - Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis

AU - Kantarjian, Hagop M.

AU - O'Brien, Susan

AU - Cortes, Jorge E.

AU - Shan, Jianqin

AU - Giles, Francis J.

AU - Rios, Mary Beth

AU - Faderl, Stefan H.

AU - Wierda, William G.

AU - Ferrajoli, Alessandra

AU - Verstovsek, Srdan

AU - Keating, Michael J.

AU - Freireich, Emil J.

AU - Talpaz, Moshe

PY - 2003/2/15

Y1 - 2003/2/15

N2 - BACKGROUND. Little is known regarding long-term prognosis among patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph-positive cells) after treatment with interferon-α. METHODS. The authors analyzed 512 patients with Ph-positive, early chronic-phase CML who were treated with interferon-based therapies between 1981-1995 for the incidence and durability of complete cytogenetic response, and in relation to long-term prognosis. RESULTS. One hundred forty patients (27%) achieved a complete cytogenetic response. Their 10-year survival rate was 78%. At the time of last follow-up, 44 patients (31%, 9% of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88-191 months); 39 patients had not received any therapy for a median of 50 months (range, 11-139 months). Analysis by reverse transcriptase-polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow-up, but only 2 had died of disease-specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response. CONCLUSIONS. Achieving a complete cytogenetic or molecular response after therapy with interferon-α appears to be associated with excellent long-term prognosis. Approximately 10% of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long-term event-free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate.

AB - BACKGROUND. Little is known regarding long-term prognosis among patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph-positive cells) after treatment with interferon-α. METHODS. The authors analyzed 512 patients with Ph-positive, early chronic-phase CML who were treated with interferon-based therapies between 1981-1995 for the incidence and durability of complete cytogenetic response, and in relation to long-term prognosis. RESULTS. One hundred forty patients (27%) achieved a complete cytogenetic response. Their 10-year survival rate was 78%. At the time of last follow-up, 44 patients (31%, 9% of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88-191 months); 39 patients had not received any therapy for a median of 50 months (range, 11-139 months). Analysis by reverse transcriptase-polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow-up, but only 2 had died of disease-specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response. CONCLUSIONS. Achieving a complete cytogenetic or molecular response after therapy with interferon-α appears to be associated with excellent long-term prognosis. Approximately 10% of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long-term event-free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate.

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KW - Complete durable cytogenetic response

KW - Interferon-α (IFN-α)

KW - Molecular response

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