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.
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.
Authors: Richard A Nash; Peter A McSweeney; Leslie J Crofford; Muneer Abidi; Chien-Shing Chen; J David Godwin; Theodore A Gooley; Leona Holmberg; Gretchen Henstorf; C Fred LeMaistre; Maureen D Mayes; Kevin T McDonagh; Bernadette McLaughlin; Jerry A Molitor; J Lee Nelson; Howard Shulman; Rainer Storb; Federico Viganego; Mark H Wener; James R Seibold; Keith M Sullivan; Daniel E Furst Journal: Blood Date: 2007-04-23 Impact factor: 22.113
Authors: Silvia Montoto; Janet Matthews; Paul Greaves; Debra Lillington; Deborah Anderson; John G Gribben; T Andrew Lister Journal: Haematologica Date: 2012-11-09 Impact factor: 9.941
Authors: Christopher J Gibson; R Coleman Lindsley; Vatche Tchekmedyian; Brenton G Mar; Jiantao Shi; Siddhartha Jaiswal; Alysia Bosworth; Liton Francisco; Jianbo He; Anita Bansal; Elizabeth A Morgan; Ann S Lacasce; Arnold S Freedman; David C Fisher; Eric Jacobsen; Philippe Armand; Edwin P Alyea; John Koreth; Vincent Ho; Robert J Soiffer; Joseph H Antin; Jerome Ritz; Sarah Nikiforow; Stephen J Forman; Franziska Michor; Donna Neuberg; Ravi Bhatia; Smita Bhatia; Benjamin L Ebert Journal: J Clin Oncol Date: 2017-01-09 Impact factor: 44.544
Authors: Mohammad Faizan Zahid; Aric Parnes; Bipin N Savani; Mark R Litzow; Shahrukh K Hashmi Journal: World J Stem Cells Date: 2016-08-26 Impact factor: 5.326