Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-hodgkin's lymphoma

D. M. Lillington, Ivana Micallef, E. Carpenter, M. J. Neat, J. A.L. Amess, J. Matthews, N. J. Foot, B. D. Young, T. A. Lister, A. Z.S. Rohatiner

Research output: Contribution to journalArticle

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Abstract

Purpose: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). Patients and Methods: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. Results: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. Conclusion: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

Original languageEnglish (US)
Pages (from-to)2472-2481
Number of pages10
JournalJournal of Clinical Oncology
Volume19
Issue number9
DOIs
StatePublished - May 1 2001
Externally publishedYes

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Acute Myeloid Leukemia
Chromosome Aberrations
Non-Hodgkin's Lymphoma
Fluorescence In Situ Hybridization
Therapeutics
Play Therapy
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 7
Whole-Body Irradiation
Hematopoietic Stem Cells
Karyotype
Cyclophosphamide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-hodgkin's lymphoma. / Lillington, D. M.; Micallef, Ivana; Carpenter, E.; Neat, M. J.; Amess, J. A.L.; Matthews, J.; Foot, N. J.; Young, B. D.; Lister, T. A.; Rohatiner, A. Z.S.

In: Journal of Clinical Oncology, Vol. 19, No. 9, 01.05.2001, p. 2472-2481.

Research output: Contribution to journalArticle

Lillington, D. M. ; Micallef, Ivana ; Carpenter, E. ; Neat, M. J. ; Amess, J. A.L. ; Matthews, J. ; Foot, N. J. ; Young, B. D. ; Lister, T. A. ; Rohatiner, A. Z.S. / Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-hodgkin's lymphoma. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 9. pp. 2472-2481.
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abstract = "Purpose: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). Patients and Methods: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. Results: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. Conclusion: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.",
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T1 - Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-hodgkin's lymphoma

AU - Lillington, D. M.

AU - Micallef, Ivana

AU - Carpenter, E.

AU - Neat, M. J.

AU - Amess, J. A.L.

AU - Matthews, J.

AU - Foot, N. J.

AU - Young, B. D.

AU - Lister, T. A.

AU - Rohatiner, A. Z.S.

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N2 - Purpose: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). Patients and Methods: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. Results: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. Conclusion: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

AB - Purpose: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). Patients and Methods: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. Results: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. Conclusion: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

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