Risk factors for leukemic transformation in patients with primary myelofibrosis

Jocelin Huang, Chin Yang Li, Ruben A. Mesa, Wentling Wu, Curtis A. Hanson, Animesh D Pardanani, Ayalew Tefferi

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

BACKGROUND. Previous prognostic studies in primary myelofibrosis have focused on risk factors for overall survival and have resulted in the establishment of several prognostic scoring systems. However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited. METHODS. The current retrospective study examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in 311 patients with primary myelofibrosis who were seen at the Mayo Clinic. RESULTS. Univariate analysis of parameters at the time of diagnosis revealed a significant association between inferior leukemia-free survival and a peripheral blood blast percentage ≥3 (P < .0001), a platelet count <100 × 10 9/L (P = .004), a monocyte count ≥1 × 109/L (P = .02), the presence of hypercatabolic symptoms (P = .03), a low hemoglobin level (P = .04), and a high leukocyte count (P = .04). The first 2 parameters were found to maintain their statistical significance during multivariate analysis. Neither leukemia-free nor overall survival was found to be affected by the presence of <3% peripheral blood blasts or JAK2V617F mutation. The evaluation of treatment effect on leukemic transformation unexpectedly revealed a significant and independent association with previous therapy with either erythropoiesis-stimulating agents (P = .004) or danazol (P = .007), even when the aforementioned prognostic indicators at the time of diagnosis were added as covariates to the multivariate model. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs. CONCLUSIONS. A peripheral blood blast percentage ≥3 and/or a platelet count <100 × 109/L at the time of diagnosis were found to be strong and independent predictors of leukemic transformation in patients with primary myelofibrosis. The unexpected association between leukemic transformation and a history of treatment with erythropoiesis-stimulating agents or danazol requires validation by prospective studies.

Original languageEnglish (US)
Pages (from-to)2726-2732
Number of pages7
JournalCancer
Volume112
Issue number12
DOIs
StatePublished - Jun 15 2008

Fingerprint

Primary Myelofibrosis
Hematinics
Danazol
Leukemia
Survival
Platelet Count
Therapeutics
Thalidomide
Hydroxyurea
Validation Studies
Leukocyte Count
Monocytes
Multivariate Analysis
Retrospective Studies
History
Prospective Studies
Mutation
Pharmaceutical Preparations

Keywords

  • Erythropoietin
  • Leukemia
  • Myeloproliferative disorder
  • Primary myelofibrosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Risk factors for leukemic transformation in patients with primary myelofibrosis. / Huang, Jocelin; Li, Chin Yang; Mesa, Ruben A.; Wu, Wentling; Hanson, Curtis A.; Pardanani, Animesh D; Tefferi, Ayalew.

In: Cancer, Vol. 112, No. 12, 15.06.2008, p. 2726-2732.

Research output: Contribution to journalArticle

Huang, Jocelin ; Li, Chin Yang ; Mesa, Ruben A. ; Wu, Wentling ; Hanson, Curtis A. ; Pardanani, Animesh D ; Tefferi, Ayalew. / Risk factors for leukemic transformation in patients with primary myelofibrosis. In: Cancer. 2008 ; Vol. 112, No. 12. pp. 2726-2732.
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abstract = "BACKGROUND. Previous prognostic studies in primary myelofibrosis have focused on risk factors for overall survival and have resulted in the establishment of several prognostic scoring systems. However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited. METHODS. The current retrospective study examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in 311 patients with primary myelofibrosis who were seen at the Mayo Clinic. RESULTS. Univariate analysis of parameters at the time of diagnosis revealed a significant association between inferior leukemia-free survival and a peripheral blood blast percentage ≥3 (P < .0001), a platelet count <100 × 10 9/L (P = .004), a monocyte count ≥1 × 109/L (P = .02), the presence of hypercatabolic symptoms (P = .03), a low hemoglobin level (P = .04), and a high leukocyte count (P = .04). The first 2 parameters were found to maintain their statistical significance during multivariate analysis. Neither leukemia-free nor overall survival was found to be affected by the presence of <3{\%} peripheral blood blasts or JAK2V617F mutation. The evaluation of treatment effect on leukemic transformation unexpectedly revealed a significant and independent association with previous therapy with either erythropoiesis-stimulating agents (P = .004) or danazol (P = .007), even when the aforementioned prognostic indicators at the time of diagnosis were added as covariates to the multivariate model. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs. CONCLUSIONS. A peripheral blood blast percentage ≥3 and/or a platelet count <100 × 109/L at the time of diagnosis were found to be strong and independent predictors of leukemic transformation in patients with primary myelofibrosis. The unexpected association between leukemic transformation and a history of treatment with erythropoiesis-stimulating agents or danazol requires validation by prospective studies.",
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T1 - Risk factors for leukemic transformation in patients with primary myelofibrosis

AU - Huang, Jocelin

AU - Li, Chin Yang

AU - Mesa, Ruben A.

AU - Wu, Wentling

AU - Hanson, Curtis A.

AU - Pardanani, Animesh D

AU - Tefferi, Ayalew

PY - 2008/6/15

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N2 - BACKGROUND. Previous prognostic studies in primary myelofibrosis have focused on risk factors for overall survival and have resulted in the establishment of several prognostic scoring systems. However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited. METHODS. The current retrospective study examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in 311 patients with primary myelofibrosis who were seen at the Mayo Clinic. RESULTS. Univariate analysis of parameters at the time of diagnosis revealed a significant association between inferior leukemia-free survival and a peripheral blood blast percentage ≥3 (P < .0001), a platelet count <100 × 10 9/L (P = .004), a monocyte count ≥1 × 109/L (P = .02), the presence of hypercatabolic symptoms (P = .03), a low hemoglobin level (P = .04), and a high leukocyte count (P = .04). The first 2 parameters were found to maintain their statistical significance during multivariate analysis. Neither leukemia-free nor overall survival was found to be affected by the presence of <3% peripheral blood blasts or JAK2V617F mutation. The evaluation of treatment effect on leukemic transformation unexpectedly revealed a significant and independent association with previous therapy with either erythropoiesis-stimulating agents (P = .004) or danazol (P = .007), even when the aforementioned prognostic indicators at the time of diagnosis were added as covariates to the multivariate model. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs. CONCLUSIONS. A peripheral blood blast percentage ≥3 and/or a platelet count <100 × 109/L at the time of diagnosis were found to be strong and independent predictors of leukemic transformation in patients with primary myelofibrosis. The unexpected association between leukemic transformation and a history of treatment with erythropoiesis-stimulating agents or danazol requires validation by prospective studies.

AB - BACKGROUND. Previous prognostic studies in primary myelofibrosis have focused on risk factors for overall survival and have resulted in the establishment of several prognostic scoring systems. However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited. METHODS. The current retrospective study examined clinical variables at the time of diagnosis and specific treatment modalities for their effect on leukemic transformation in 311 patients with primary myelofibrosis who were seen at the Mayo Clinic. RESULTS. Univariate analysis of parameters at the time of diagnosis revealed a significant association between inferior leukemia-free survival and a peripheral blood blast percentage ≥3 (P < .0001), a platelet count <100 × 10 9/L (P = .004), a monocyte count ≥1 × 109/L (P = .02), the presence of hypercatabolic symptoms (P = .03), a low hemoglobin level (P = .04), and a high leukocyte count (P = .04). The first 2 parameters were found to maintain their statistical significance during multivariate analysis. Neither leukemia-free nor overall survival was found to be affected by the presence of <3% peripheral blood blasts or JAK2V617F mutation. The evaluation of treatment effect on leukemic transformation unexpectedly revealed a significant and independent association with previous therapy with either erythropoiesis-stimulating agents (P = .004) or danazol (P = .007), even when the aforementioned prognostic indicators at the time of diagnosis were added as covariates to the multivariate model. In contrast, leukemia-free survival was not found to be affected by a treatment history with hydroxyurea, thalidomide, or other drugs. CONCLUSIONS. A peripheral blood blast percentage ≥3 and/or a platelet count <100 × 109/L at the time of diagnosis were found to be strong and independent predictors of leukemic transformation in patients with primary myelofibrosis. The unexpected association between leukemic transformation and a history of treatment with erythropoiesis-stimulating agents or danazol requires validation by prospective studies.

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KW - Leukemia

KW - Myeloproliferative disorder

KW - Primary myelofibrosis

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