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G. Corkidi - One of the best experts on this subject based on the ideXlab platform.
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Inter-extrema profile analysis for a texture coarseness estimate in automatic Metaphase finding
ISPA 2001. Proceedings of the 2nd International Symposium on Image and Signal Processing and Analysis. In conjunction with 23rd International Conferen, 2001Co-Authors: L. Vega-alvarado, J. Marquez, G. CorkidiAbstract:As part of a larger effort for automated Metaphase finding in cell proliferation studies, we report our experiences with a texture coarseness measure of intensity profile samples. This measure is highly specific to gray-level inter-extrema roughness features in microscopic images of Metaphase spreads. Chromosome fragments produce patterns of pixels at low-resolution, and the local neighborhood of their individual extrema presents a characteristic coarseness. Artifacts as well as other cytological objects like stimulated or non-stimulated nuclei give rise to similar discrete patterns. Using a stereological-based approach, we propose the inter-extrema profile range (IEPR) analysis, which allows the estimation of 2D texture coarseness through statistical features of 1D signatures. Results of its use on images of fields of Metaphases and artifacts are compared with the mean depth-width ratio of extrema and other texture measures.
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A neural network based workstation for automated cell proliferation analysis
2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2001Co-Authors: Arambula F. Cosio, L. Vega, Herrera A. Becerra, Prieto R. Melendez, G. CorkidiAbstract:In this paper is reported the development of a neural network (NN) based workstation for automated cell proliferation analysis, of cytological microscope images. The software of the system assists the expert biotechnologist during cell proliferation and chromosome aberration studies by automatically identifying Metaphase spreads and stimulated nuclei on each digital image. After manual edition of Metaphase false positives, the system automatically calculates the mitotic index (MI) i.e. the ratio of Metaphases to stimulated nuclei of a given tissue sample. The system reported has been able to classify correctly approximately 91% of the Metaphases and stimulated nuclei, in a test set of 191 mitosis, 331 nuclei, and 387 artefacts, obtained from 30 different microscope slides. Manual edition of false positives from the Metaphase classification results allows the calculation of the MI with an error of 6.5%.
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Automatic Metaphase finding by inter-chromosome extrema profile analysis
2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2001Co-Authors: L. Vega-alvarado, J. Marquez, G. CorkidiAbstract:In this paper we report our experiences with a new texture coarseness measure, as a step towards automation of Metaphase finding in cell proliferation studies. This measure is highly specific to grey-level inter-chromosome coarseness features in microscopic images of Metaphase spreads, and allows to quantify the texture of the cytological objects analysing the intensity profile between chromosome-extrema samples. Chromosome fragments produce patterns of pixels at low-resolution, and the local neighbourhood of their individual extrema presents a characteristic coarseness, along intensity profiles on random-oriented test lines. Results of its use on images of fields of Metaphases and artefacts are compared with some representative texture measures, outperforming Metaphase detection and artefacts elimination. This coarseness feature provides a specific Metaphase signature that can be used in conjunction with other morphological and textural parameters for automated Metaphase discrimination.
Rhett P Ketterling - One of the best experts on this subject based on the ideXlab platform.
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Metaphase Cytogenetics for Risk Stratification in Newly Diagnosed Multiple Myeloma
Blood, 2019Co-Authors: Patrick W. Mellors, Rhett P Ketterling, Moritz Binder, Patricia T. Griepp, Linda B. Baughn, Francis K. Buadi, Martha Q. Lacy, Morie A. Gertz, Angela Dispenzieri, Suzanne HaymannAbstract:Introduction: Abnormal Metaphase cytogenetics are associated with inferior survival in newly diagnosed multiple myeloma (MM). These abnormalities are only detected in one third of cases due to the low proliferative rate of plasma cells. It is unknown if Metaphase cytogenetics improve risk stratification when using contemporary prognostic models such as the revised international staging system (R-ISS), which incorporates interphase fluorescence in situ hybridization (FISH). Aims: The aims of this study were to 1) characterize the association between abnormalities on Metaphase cytogenetics and overall survival (OS) in newly diagnosed MM treated with novel agents and 2) evaluate whether the addition of Metaphase cytogenetics to R-ISS, age, and plasma cell labeling index (PCLI) improves model discrimination with respect to OS. Methods: We analyzed a retrospective cohort of 483 newly diagnosed MM patients treated with proteasome inhibitors (PI) and/or immunomodulators (IMID) who had Metaphase cytogenetics performed prior to initiation of therapy. Abnormal Metaphase cytogenetics were defined as MM specific abnormalities, while normal Metaphase cytogenetics included constitutional cytogenetic variants, age-related Y chromosome loss, and normal Metaphase karyotypes. Multivariable adjusted proportional hazards regression models were fit for the association between known prognostic factors and OS. Covariates associated with inferior OS on multivariable analysis included R-ISS stage, age ≥ 70, PCLI ≥ 2, and abnormal Metaphase cytogenetics. We devised a risk scoring system weighted by their respective hazard ratios (R-ISS II +1, R-ISS III + 2, age ≥ 70 +2, PCLI ≥ 2 +1, Metaphase cytogenetic abnormalities + 1). Low (LR), intermediate (IR), and high risk (HR) groups were established based on risk scores of 0-1, 2-3, and 4-5 in modeling without Metaphase cytogenetics, and scores of 0-1, 2-3, and 4-6 in modeling incorporating Metaphase cytogenetics, respectively. Survival estimates were calculated using the Kaplan-Meier method. Survival analysis was stratified by LR, IR, and HR groups in models 1) excluding Metaphase cytogenetics 2) including Metaphase cytogenetics and 3) including Metaphase cytogenetics, with IR stratified by presence and absence of Metaphase cytogenetic abnormalities. Survival estimates were compared between groups using the log-rank test. Harrell's C was used to compare the predictive power of risk modeling with and without Metaphase cytogenetics. Results: Median age at diagnosis was 66 (31-95), 281 patients (58%) were men, median follow up was 5.5 years (0.04-14.4), and median OS was 6.4 years (95% CI 5.7-6.8). Ninety-seven patients (20%) were R-ISS stage I, 318 (66%) stage II, and 68 (14%) stage III. One-hundred and fourteen patients (24%) had high-risk abnormalities by FISH, and 115 (24%) had abnormal Metaphase cytogenetics. Three-hundred and thirteen patients (65%) received an IMID, 119 (25%) a PI, 51 (10%) received IMID and PI, and 137 (28%) underwent upfront autologous hematopoietic stem cell transplantation (ASCT). On multivariable analysis, R-ISS (HR 1.59, 95% CI 1.29-1.97, p < 0.001), age ≥ 70 (HR 2.32, 95% CI 1.83-2.93, p < 0.001), PCLI ≥ 2, (HR 1.52, 95% CI 1.16-2.00, p=0.002) and abnormalities on Metaphase cytogenetics (HR 1.35, 95% CI 1.05-1.75, p=0.019) were associated with inferior OS. IR and HR groups experienced significantly worse survival compared to LR groups in models excluding (Figure 1A) and including (Figure 1B) the effect of Metaphase cytogenetics (p < 0.001 for all comparisons). However, the inclusion of Metaphase cytogenetics did not improve discrimination. Likewise, subgroup analysis of IR patients by the presence or absence of Metaphase cytogenetic abnormalities did not improve risk stratification (Figure 1C) (p < 0.001). The addition of Metaphase cytogenetics to risk modeling with R-ISS stage, age ≥ 70, and PCLI ≥ 2 did not improve prognostic performance when evaluated by Harrell's C (c=0.636 without cytogenetics, c=0.642 with cytogenetics, absolute difference 0.005, 95% CI 0.002-0.012, p=0.142). Conclusions: Abnormalities on Metaphase cytogenetics at diagnosis are associated with inferior OS in MM when accounting for the effects of R-ISS, age, and PCLI. However, the addition of Metaphase cytogenetics to prognostic modeling incorporating these covariates did not significantly improve risk stratification. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Alnylam: Research Funding; Celgene: Research Funding; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding. Kapoor:Celgene: Honoraria; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Glaxo Smith Kline: Research Funding. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.
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The Effect of Number of Metaphases Studied and Abnormal Metaphase Percentage On Cytogenetic Risk Stratification in Primary Myelofibrosis
Blood, 2012Co-Authors: Shaina A Rozell, Rhett P Ketterling, Biruk Mengistu, Naseema Gangat, Curtis A. Hanson, Ryan A. Knudson, Animesh Pardanani, Ayalew TefferiAbstract:Abstract 1742 Background Karyotype is one of the most potent and reproducible risk factors for both overall (OS) and leukemia-free (LFS) survival in primary myelofibrosis (PMF) ( Blood 2011;118:4595 ). It is currently not clear if the number of Metaphases studied or the abnormal Metaphase percentage alters this prognostic impact. Methods: An updated Mayo Clinic database of karyotypically- and DIPSS-plus-annotated patients with PMF was used to identify a consecutive series of patients and their cytogenetic information obtained at time of referral was centrally re-reviewed. Cytogenetic results were interpreted and reported according to the International System for Human Cytogenetic Nomenclature; abnormal karyotype was defined by the presence of at least 2 Metaphases with structural abnormalities or monosomy or 3 Metaphases with polysomy, regardless of number of Metaphases examined. For this particular study, the presence of less than 20 evaluable Metaphases did not disqualify patients. “Very high risk” karyotype included monosomal karyotype, inv(3) or i(17q) abnormalities ( Blood 2011;118:4595 ). “unfavorable” karyotype included complex or any sole or two abnormalities that included +8, −7/7q-, -5/5q-, inv(3), i(17q), 12p-, or 11q23 rearrangement ( Blood 2011;118:4595 ). All other cytogenetic abnormalities were considered “favorable” Results: A total of 590 patients (median age 65 years; range 19–89 years) including 424 (72%) males. The DIPSS-plus ( JCO 2011;29:392 ) risk distribution was 40% high, 39% intermediate-2, 12% intermediate-1 and 9% low. Cytogenetic findings included 17 (3%) very high risk, 69 (12%) unfavorable, 165 (28%) favorable and 339 (57%) normal karyotypes. The number of bone marrow Metaphases studied to report these cytogenetic findings were ≥20 in 468 (79%) patients, 11 to 19 in 71 (12%) patients and ≤10 in 51 (9%) patients; the proportion of cases studied with ≥20 Metaphases were 53% for very high risk, 74% for unfavorable, 83% for favorable and 80% for normal karyotype (p=0.006). Among patients with abnormal karyotype, the abnormal Metaphase percentage was ≥75% in 148 (59%) patients, 50 to 74% in 36 (15%) patients, 26 to 49% in 27 (11%) patients and ≤25% in 38 (15%) patients; the proportion of patients with ≥75% was 59% for very high risk, 67% for unfavorable and 56% for favorable karyotypes (p=0.70). As expected, OS was significantly different among very high risk, unfavorable, favorable and normal karyotype patients with respective median survivals of 8, 23, 41 and 57 months (p
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additional cytogenetic abnormalities and or philadelphia chromosome Metaphase mosaicism might adversely influence survival and imatinib response in chronic myeloid leukemia
Blood, 2006Co-Authors: Andrew P Landstrom, Gordon W Dewald, Rhett P Ketterling, Ryan A. Knudson, Ayalew TefferiAbstract:Background: Chronic myeloid leukemia (CML) is invariably associated with the reciprocal translocation of BCR and ABL to form the Philadelphia chromosome (Ph), t(9;22)(q34;q11). At diagnosis, a small proportion of patients display additional cytogenetic abnormalities and/or a variable proportion of cytogenetically normal Metaphases that coexist with Ph-positive Metaphases. The objective of the current study was to examine the prognostic relevance of these two scenarios. Methods: The study population consisted of 65 (47.7% female) consecutive, newly diagnosed CML patients seen at the Mayo Clinic with a median age of 59 years. 44.5 percent were initially treated with interferon alpha (IFN) resulting in complete cytogenetic remission in 10.7 percent for a median length of 5.83 years, partial cytogenetic remission in 3.57 percent for a median length of 2 years. 55.5 percent were treated with imatinib (Gleevec) resulting in complete cytogenetic remission in 54.1 percent for a median length of 3.08 years, partial cytogenetic remission in 13.5% for a median length of 1.08 years. Results: Survival at five years through Kaplan-Meier analysis was approximately 92 percent in patients demonstrating only the Ph chromosome (n = 53), versus 60 percent in patients with additional chromosomal abnormalities (n = 12; p < 0.0001 by both Logrank and Breslow-Gehan-Wilcox analysis). Furthermore, patients with additional chromosomal abnormalities demonstrated lower rates of either complete or partial cytogenetic remission with imatinib therapy. Similarly, five year survival of patients with less than 90% Ph-positive Metaphases at diagnosis (n = 4) was approximately 60% compared to 92% in patients with greater than 90% Ph-positive Metaphases (n = 61; p = 0.01 by Logrank and p = 0.001 by Breslow-Gehan-Wilcox analysis). Additionally, the former group of patients was significantly less responsive to imatinib. Finally, there was significant correlation between Ph-positive Metaphase mosaicism and the presence of additional chromosomal abnormalities (p = 0.05). Conclusion: Although it is tempting to speculate the possibility that Ph-chromosome mosaicism and/or additional cytogenetic abnormalities at presentation of CML is a surrogate for the presence of Ph-negative imatinib-resistant clones, the preliminary results from the current study require validation from a larger study. ![Figure][1] Figure ![Figure][1] Figure [1]: pending:yes
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relationship of patient survival and chromosome anomalies detected in Metaphase and or interphase cells at diagnosis of myeloma
Blood, 2005Co-Authors: Gordon W Dewald, Terry M Therneau, Dirk R Larson, Stephanie R Fink, Stephanie A Smoley, Sarah F Paternoster, Adewale Adeyinka, Rhett P Ketterling, Daniel L Van Dyke, Rafael FonsecaAbstract:The clinical efficacy of evaluating genetic anomalies in Metaphase cells versus interphase nuclei for multiple myeloma (MM) is poorly understood. Therefore, survival for 154 patients with newly diagnosed untreated MM was compared with results from analysis of Metaphase and interphase cells. Metaphases were studied by conventional cytogenetics and fluorescent-labeled DNA probes (fluorescence in situ hybridization [FISH]), whereas inter-phase nuclei were evaluated only by FISH. All FISH studies were done using DNA probes to detect t(4;14)(p16;q32), t(11;14)(q13;q32), t(14;16)(q32;q23), del(17) (p13.1), and chromosome 13 anomalies. Metaphases were abnormal by cytogenetics and/or Metaphase FISH in 61 (40%) patients. Abnormal interphase nuclei were observed in 133 (86%) patients, including each patient with abnormal Metaphases. FISH was a necessary adjunct to cytogenetics to detect t(4;14) and t(14;16) in Metaphase cells. Patient survival was especially poor for patients with greater than 50% abnormal interphase nuclei, although this result was more likely due to level of plasma cells than specific chromosome anomalies. For Metaphase data, patients with t(4;14), t(14;16), del(17) (p13.1), and/or chromosome 13 anomalies (primarily monosomy 13) had poor survival. A different outcome was observed for interphase data as patients with t(4;14) or t(14;16) had poor survival, whereas patients with chromosome 13 anomalies had intermediate survival: interphase FISH did not substitute for Metaphase analysis.
Ayalew Tefferi - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Number of Metaphases Studied and Abnormal Metaphase Percentage On Cytogenetic Risk Stratification in Primary Myelofibrosis
Blood, 2012Co-Authors: Shaina A Rozell, Rhett P Ketterling, Biruk Mengistu, Naseema Gangat, Curtis A. Hanson, Ryan A. Knudson, Animesh Pardanani, Ayalew TefferiAbstract:Abstract 1742 Background Karyotype is one of the most potent and reproducible risk factors for both overall (OS) and leukemia-free (LFS) survival in primary myelofibrosis (PMF) ( Blood 2011;118:4595 ). It is currently not clear if the number of Metaphases studied or the abnormal Metaphase percentage alters this prognostic impact. Methods: An updated Mayo Clinic database of karyotypically- and DIPSS-plus-annotated patients with PMF was used to identify a consecutive series of patients and their cytogenetic information obtained at time of referral was centrally re-reviewed. Cytogenetic results were interpreted and reported according to the International System for Human Cytogenetic Nomenclature; abnormal karyotype was defined by the presence of at least 2 Metaphases with structural abnormalities or monosomy or 3 Metaphases with polysomy, regardless of number of Metaphases examined. For this particular study, the presence of less than 20 evaluable Metaphases did not disqualify patients. “Very high risk” karyotype included monosomal karyotype, inv(3) or i(17q) abnormalities ( Blood 2011;118:4595 ). “unfavorable” karyotype included complex or any sole or two abnormalities that included +8, −7/7q-, -5/5q-, inv(3), i(17q), 12p-, or 11q23 rearrangement ( Blood 2011;118:4595 ). All other cytogenetic abnormalities were considered “favorable” Results: A total of 590 patients (median age 65 years; range 19–89 years) including 424 (72%) males. The DIPSS-plus ( JCO 2011;29:392 ) risk distribution was 40% high, 39% intermediate-2, 12% intermediate-1 and 9% low. Cytogenetic findings included 17 (3%) very high risk, 69 (12%) unfavorable, 165 (28%) favorable and 339 (57%) normal karyotypes. The number of bone marrow Metaphases studied to report these cytogenetic findings were ≥20 in 468 (79%) patients, 11 to 19 in 71 (12%) patients and ≤10 in 51 (9%) patients; the proportion of cases studied with ≥20 Metaphases were 53% for very high risk, 74% for unfavorable, 83% for favorable and 80% for normal karyotype (p=0.006). Among patients with abnormal karyotype, the abnormal Metaphase percentage was ≥75% in 148 (59%) patients, 50 to 74% in 36 (15%) patients, 26 to 49% in 27 (11%) patients and ≤25% in 38 (15%) patients; the proportion of patients with ≥75% was 59% for very high risk, 67% for unfavorable and 56% for favorable karyotypes (p=0.70). As expected, OS was significantly different among very high risk, unfavorable, favorable and normal karyotype patients with respective median survivals of 8, 23, 41 and 57 months (p
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additional cytogenetic abnormalities and or philadelphia chromosome Metaphase mosaicism might adversely influence survival and imatinib response in chronic myeloid leukemia
Blood, 2006Co-Authors: Andrew P Landstrom, Gordon W Dewald, Rhett P Ketterling, Ryan A. Knudson, Ayalew TefferiAbstract:Background: Chronic myeloid leukemia (CML) is invariably associated with the reciprocal translocation of BCR and ABL to form the Philadelphia chromosome (Ph), t(9;22)(q34;q11). At diagnosis, a small proportion of patients display additional cytogenetic abnormalities and/or a variable proportion of cytogenetically normal Metaphases that coexist with Ph-positive Metaphases. The objective of the current study was to examine the prognostic relevance of these two scenarios. Methods: The study population consisted of 65 (47.7% female) consecutive, newly diagnosed CML patients seen at the Mayo Clinic with a median age of 59 years. 44.5 percent were initially treated with interferon alpha (IFN) resulting in complete cytogenetic remission in 10.7 percent for a median length of 5.83 years, partial cytogenetic remission in 3.57 percent for a median length of 2 years. 55.5 percent were treated with imatinib (Gleevec) resulting in complete cytogenetic remission in 54.1 percent for a median length of 3.08 years, partial cytogenetic remission in 13.5% for a median length of 1.08 years. Results: Survival at five years through Kaplan-Meier analysis was approximately 92 percent in patients demonstrating only the Ph chromosome (n = 53), versus 60 percent in patients with additional chromosomal abnormalities (n = 12; p < 0.0001 by both Logrank and Breslow-Gehan-Wilcox analysis). Furthermore, patients with additional chromosomal abnormalities demonstrated lower rates of either complete or partial cytogenetic remission with imatinib therapy. Similarly, five year survival of patients with less than 90% Ph-positive Metaphases at diagnosis (n = 4) was approximately 60% compared to 92% in patients with greater than 90% Ph-positive Metaphases (n = 61; p = 0.01 by Logrank and p = 0.001 by Breslow-Gehan-Wilcox analysis). Additionally, the former group of patients was significantly less responsive to imatinib. Finally, there was significant correlation between Ph-positive Metaphase mosaicism and the presence of additional chromosomal abnormalities (p = 0.05). Conclusion: Although it is tempting to speculate the possibility that Ph-chromosome mosaicism and/or additional cytogenetic abnormalities at presentation of CML is a surrogate for the presence of Ph-negative imatinib-resistant clones, the preliminary results from the current study require validation from a larger study. ![Figure][1] Figure ![Figure][1] Figure [1]: pending:yes
Arambula F. Cosio - One of the best experts on this subject based on the ideXlab platform.
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A neural network based workstation for automated cell proliferation analysis
2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2001Co-Authors: Arambula F. Cosio, L. Vega, Herrera A. Becerra, Prieto R. Melendez, G. CorkidiAbstract:In this paper is reported the development of a neural network (NN) based workstation for automated cell proliferation analysis, of cytological microscope images. The software of the system assists the expert biotechnologist during cell proliferation and chromosome aberration studies by automatically identifying Metaphase spreads and stimulated nuclei on each digital image. After manual edition of Metaphase false positives, the system automatically calculates the mitotic index (MI) i.e. the ratio of Metaphases to stimulated nuclei of a given tissue sample. The system reported has been able to classify correctly approximately 91% of the Metaphases and stimulated nuclei, in a test set of 191 mitosis, 331 nuclei, and 387 artefacts, obtained from 30 different microscope slides. Manual edition of false positives from the Metaphase classification results allows the calculation of the MI with an error of 6.5%.
Gordon W Dewald - One of the best experts on this subject based on the ideXlab platform.
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additional cytogenetic abnormalities and or philadelphia chromosome Metaphase mosaicism might adversely influence survival and imatinib response in chronic myeloid leukemia
Blood, 2006Co-Authors: Andrew P Landstrom, Gordon W Dewald, Rhett P Ketterling, Ryan A. Knudson, Ayalew TefferiAbstract:Background: Chronic myeloid leukemia (CML) is invariably associated with the reciprocal translocation of BCR and ABL to form the Philadelphia chromosome (Ph), t(9;22)(q34;q11). At diagnosis, a small proportion of patients display additional cytogenetic abnormalities and/or a variable proportion of cytogenetically normal Metaphases that coexist with Ph-positive Metaphases. The objective of the current study was to examine the prognostic relevance of these two scenarios. Methods: The study population consisted of 65 (47.7% female) consecutive, newly diagnosed CML patients seen at the Mayo Clinic with a median age of 59 years. 44.5 percent were initially treated with interferon alpha (IFN) resulting in complete cytogenetic remission in 10.7 percent for a median length of 5.83 years, partial cytogenetic remission in 3.57 percent for a median length of 2 years. 55.5 percent were treated with imatinib (Gleevec) resulting in complete cytogenetic remission in 54.1 percent for a median length of 3.08 years, partial cytogenetic remission in 13.5% for a median length of 1.08 years. Results: Survival at five years through Kaplan-Meier analysis was approximately 92 percent in patients demonstrating only the Ph chromosome (n = 53), versus 60 percent in patients with additional chromosomal abnormalities (n = 12; p < 0.0001 by both Logrank and Breslow-Gehan-Wilcox analysis). Furthermore, patients with additional chromosomal abnormalities demonstrated lower rates of either complete or partial cytogenetic remission with imatinib therapy. Similarly, five year survival of patients with less than 90% Ph-positive Metaphases at diagnosis (n = 4) was approximately 60% compared to 92% in patients with greater than 90% Ph-positive Metaphases (n = 61; p = 0.01 by Logrank and p = 0.001 by Breslow-Gehan-Wilcox analysis). Additionally, the former group of patients was significantly less responsive to imatinib. Finally, there was significant correlation between Ph-positive Metaphase mosaicism and the presence of additional chromosomal abnormalities (p = 0.05). Conclusion: Although it is tempting to speculate the possibility that Ph-chromosome mosaicism and/or additional cytogenetic abnormalities at presentation of CML is a surrogate for the presence of Ph-negative imatinib-resistant clones, the preliminary results from the current study require validation from a larger study. ![Figure][1] Figure ![Figure][1] Figure [1]: pending:yes
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relationship of patient survival and chromosome anomalies detected in Metaphase and or interphase cells at diagnosis of myeloma
Blood, 2005Co-Authors: Gordon W Dewald, Terry M Therneau, Dirk R Larson, Stephanie R Fink, Stephanie A Smoley, Sarah F Paternoster, Adewale Adeyinka, Rhett P Ketterling, Daniel L Van Dyke, Rafael FonsecaAbstract:The clinical efficacy of evaluating genetic anomalies in Metaphase cells versus interphase nuclei for multiple myeloma (MM) is poorly understood. Therefore, survival for 154 patients with newly diagnosed untreated MM was compared with results from analysis of Metaphase and interphase cells. Metaphases were studied by conventional cytogenetics and fluorescent-labeled DNA probes (fluorescence in situ hybridization [FISH]), whereas inter-phase nuclei were evaluated only by FISH. All FISH studies were done using DNA probes to detect t(4;14)(p16;q32), t(11;14)(q13;q32), t(14;16)(q32;q23), del(17) (p13.1), and chromosome 13 anomalies. Metaphases were abnormal by cytogenetics and/or Metaphase FISH in 61 (40%) patients. Abnormal interphase nuclei were observed in 133 (86%) patients, including each patient with abnormal Metaphases. FISH was a necessary adjunct to cytogenetics to detect t(4;14) and t(14;16) in Metaphase cells. Patient survival was especially poor for patients with greater than 50% abnormal interphase nuclei, although this result was more likely due to level of plasma cells than specific chromosome anomalies. For Metaphase data, patients with t(4;14), t(14;16), del(17) (p13.1), and/or chromosome 13 anomalies (primarily monosomy 13) had poor survival. A different outcome was observed for interphase data as patients with t(4;14) or t(14;16) had poor survival, whereas patients with chromosome 13 anomalies had intermediate survival: interphase FISH did not substitute for Metaphase analysis.
