Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase

Hagop M. Kantarjian, Jianqin Shan, Terry Smith, Moshe Talpaz, Peter Kozuch, Mary Beth Rios, Jorge Cortes, Francis J. Giles, Susan O'Brien

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Achievement of minimal tumor burden, such as complete response, has been accepted as a surrogate marker for improved survival in many solid and hematologic carcinomas. Several new agents have been approved recently for orphan disease indications or unmet medical needs, based on response analyses. This has not been the case for chronic myelogenous leukemia in the blastic phase (CML-BP), despite its poor prognosis, because response has not been proven to be a valuable endpoint for survival prolongation. The purpose of this study was to analyze the effect of response in CML-BP on survival prolongation. STUDY GROUP AND METHODS. In total, 328 patients with CML-BP referred from 1989 to 1999 were studied; 311 patients received therapy for CML-BP, and 275 were evaluable for response. Blastic phase CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Treatment responses were reviewed and categorized as proposed in previous large studies. Four categoric response groups were defined further based on significant differences in outcome: cytogenetic response, hematologic response, bone marrow improvement, and failure. The association of treatment response with survival was evaluated by multivariate and landmark analyses. RESULTS. The association of response with survival was analyzed among the 275 patients who had evaluable responses, and follow-up information was documented. Univariate analysis of pretreatment characteristics found performance status, hemoglobin levels, platelet counts, peripheral blasts, additional chromosomal abnormalities, and blastic phase morphology as showing significant associations with survival (P < 0.1). A multivariate analysis found platelet counts and blastic morphology as independent significant factors associated with survival (P < 0.05). A landmark analysis conducted at 8 weeks from start of therapy showed the beneficial effect of achieving response on survival prolongation (P < 0.001). A repeat multivariate at the 8-week landmark time in the 240 patients alive at that time, which included pretreatment characteristics and treatment response, confirmed the independent significant association of morphology (P = 0.003), platelet counts (P = 0.04), and response (P < 0.001) with survival. CONCLUSIONS. Response to therapy is a significant independent factor associated with survival prolongation and maybe an acceptable therapeutic endpoint for approving new treatments in CML-BP.

Original languageEnglish (US)
Pages (from-to)2501-2507
Number of pages7
JournalCancer
Volume92
Issue number10
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Survival
Platelet Count
Therapeutics
Multivariate Analysis
Bone Marrow
Rare Diseases
Tumor Burden
Cytogenetics
Chromosome Aberrations
Hemoglobins
Biomarkers
Carcinoma

Keywords

  • Blastic phase
  • Chronic myeloid
  • Myelogenous leukemia
  • Response
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase. / Kantarjian, Hagop M.; Shan, Jianqin; Smith, Terry; Talpaz, Moshe; Kozuch, Peter; Rios, Mary Beth; Cortes, Jorge; Giles, Francis J.; O'Brien, Susan.

In: Cancer, Vol. 92, No. 10, 15.11.2001, p. 2501-2507.

Research output: Contribution to journalArticle

Kantarjian, Hagop M. ; Shan, Jianqin ; Smith, Terry ; Talpaz, Moshe ; Kozuch, Peter ; Rios, Mary Beth ; Cortes, Jorge ; Giles, Francis J. ; O'Brien, Susan. / Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase. In: Cancer. 2001 ; Vol. 92, No. 10. pp. 2501-2507.
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abstract = "BACKGROUND. Achievement of minimal tumor burden, such as complete response, has been accepted as a surrogate marker for improved survival in many solid and hematologic carcinomas. Several new agents have been approved recently for orphan disease indications or unmet medical needs, based on response analyses. This has not been the case for chronic myelogenous leukemia in the blastic phase (CML-BP), despite its poor prognosis, because response has not been proven to be a valuable endpoint for survival prolongation. The purpose of this study was to analyze the effect of response in CML-BP on survival prolongation. STUDY GROUP AND METHODS. In total, 328 patients with CML-BP referred from 1989 to 1999 were studied; 311 patients received therapy for CML-BP, and 275 were evaluable for response. Blastic phase CML was defined by the presence of 30{\%} or more blasts in the blood or bone marrow, or extramedullary disease. Treatment responses were reviewed and categorized as proposed in previous large studies. Four categoric response groups were defined further based on significant differences in outcome: cytogenetic response, hematologic response, bone marrow improvement, and failure. The association of treatment response with survival was evaluated by multivariate and landmark analyses. RESULTS. The association of response with survival was analyzed among the 275 patients who had evaluable responses, and follow-up information was documented. Univariate analysis of pretreatment characteristics found performance status, hemoglobin levels, platelet counts, peripheral blasts, additional chromosomal abnormalities, and blastic phase morphology as showing significant associations with survival (P < 0.1). A multivariate analysis found platelet counts and blastic morphology as independent significant factors associated with survival (P < 0.05). A landmark analysis conducted at 8 weeks from start of therapy showed the beneficial effect of achieving response on survival prolongation (P < 0.001). A repeat multivariate at the 8-week landmark time in the 240 patients alive at that time, which included pretreatment characteristics and treatment response, confirmed the independent significant association of morphology (P = 0.003), platelet counts (P = 0.04), and response (P < 0.001) with survival. CONCLUSIONS. Response to therapy is a significant independent factor associated with survival prolongation and maybe an acceptable therapeutic endpoint for approving new treatments in CML-BP.",
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T1 - Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase

AU - Kantarjian, Hagop M.

AU - Shan, Jianqin

AU - Smith, Terry

AU - Talpaz, Moshe

AU - Kozuch, Peter

AU - Rios, Mary Beth

AU - Cortes, Jorge

AU - Giles, Francis J.

AU - O'Brien, Susan

PY - 2001/11/15

Y1 - 2001/11/15

N2 - BACKGROUND. Achievement of minimal tumor burden, such as complete response, has been accepted as a surrogate marker for improved survival in many solid and hematologic carcinomas. Several new agents have been approved recently for orphan disease indications or unmet medical needs, based on response analyses. This has not been the case for chronic myelogenous leukemia in the blastic phase (CML-BP), despite its poor prognosis, because response has not been proven to be a valuable endpoint for survival prolongation. The purpose of this study was to analyze the effect of response in CML-BP on survival prolongation. STUDY GROUP AND METHODS. In total, 328 patients with CML-BP referred from 1989 to 1999 were studied; 311 patients received therapy for CML-BP, and 275 were evaluable for response. Blastic phase CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Treatment responses were reviewed and categorized as proposed in previous large studies. Four categoric response groups were defined further based on significant differences in outcome: cytogenetic response, hematologic response, bone marrow improvement, and failure. The association of treatment response with survival was evaluated by multivariate and landmark analyses. RESULTS. The association of response with survival was analyzed among the 275 patients who had evaluable responses, and follow-up information was documented. Univariate analysis of pretreatment characteristics found performance status, hemoglobin levels, platelet counts, peripheral blasts, additional chromosomal abnormalities, and blastic phase morphology as showing significant associations with survival (P < 0.1). A multivariate analysis found platelet counts and blastic morphology as independent significant factors associated with survival (P < 0.05). A landmark analysis conducted at 8 weeks from start of therapy showed the beneficial effect of achieving response on survival prolongation (P < 0.001). A repeat multivariate at the 8-week landmark time in the 240 patients alive at that time, which included pretreatment characteristics and treatment response, confirmed the independent significant association of morphology (P = 0.003), platelet counts (P = 0.04), and response (P < 0.001) with survival. CONCLUSIONS. Response to therapy is a significant independent factor associated with survival prolongation and maybe an acceptable therapeutic endpoint for approving new treatments in CML-BP.

AB - BACKGROUND. Achievement of minimal tumor burden, such as complete response, has been accepted as a surrogate marker for improved survival in many solid and hematologic carcinomas. Several new agents have been approved recently for orphan disease indications or unmet medical needs, based on response analyses. This has not been the case for chronic myelogenous leukemia in the blastic phase (CML-BP), despite its poor prognosis, because response has not been proven to be a valuable endpoint for survival prolongation. The purpose of this study was to analyze the effect of response in CML-BP on survival prolongation. STUDY GROUP AND METHODS. In total, 328 patients with CML-BP referred from 1989 to 1999 were studied; 311 patients received therapy for CML-BP, and 275 were evaluable for response. Blastic phase CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Treatment responses were reviewed and categorized as proposed in previous large studies. Four categoric response groups were defined further based on significant differences in outcome: cytogenetic response, hematologic response, bone marrow improvement, and failure. The association of treatment response with survival was evaluated by multivariate and landmark analyses. RESULTS. The association of response with survival was analyzed among the 275 patients who had evaluable responses, and follow-up information was documented. Univariate analysis of pretreatment characteristics found performance status, hemoglobin levels, platelet counts, peripheral blasts, additional chromosomal abnormalities, and blastic phase morphology as showing significant associations with survival (P < 0.1). A multivariate analysis found platelet counts and blastic morphology as independent significant factors associated with survival (P < 0.05). A landmark analysis conducted at 8 weeks from start of therapy showed the beneficial effect of achieving response on survival prolongation (P < 0.001). A repeat multivariate at the 8-week landmark time in the 240 patients alive at that time, which included pretreatment characteristics and treatment response, confirmed the independent significant association of morphology (P = 0.003), platelet counts (P = 0.04), and response (P < 0.001) with survival. CONCLUSIONS. Response to therapy is a significant independent factor associated with survival prolongation and maybe an acceptable therapeutic endpoint for approving new treatments in CML-BP.

KW - Blastic phase

KW - Chronic myeloid

KW - Myelogenous leukemia

KW - Response

KW - Survival

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