Ignite Creation Date:
2024-05-06 @ 12:14 PM
Last Modification Date:
2024-10-26 @ 12:56 PM
Study NCT ID:
NCT03719183
Status:
COMPLETED
Last Update Posted:
2022-03-09
First Post:
2018-10-23
Brief Title:
Comparison of Diagnostic Yield Among M-FISH FISH Probe Panel and Conventional Cytogenetic Analysis in AML
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Comparison of Diagnostic Yield Among Multiplex Fluorescent in Situ Hybridization Fluorescent in Situ Hybridization Probe Panel and Conventional Cytogenetic Studies in Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Conventional cytogenetic studies have been the gold standard for more than five decades for detecting genetic alterations that are greater than 10 Mb mega base pairs in size Conventional cytogenetic studies have paved the way in identifying specific chromosomal aberrations associated with clinically and morphologically definitive subsets of hematological neoplasms
Fluorescence in situ hybridization FISH has become a reliable and rapid complementary test in targeting critical genetic events associated with diagnostics and prognosis in hematological neoplasms
In the current health care environment which increasingly focuses on value and efficiency it is critical for pathologists and clinicians to effectively navigate this environment and judiciously incorporate these high-complexity and expensive techniques into routine patient care While conventional karyotyping provides a comprehensive view of the genome FISH can detect cryptic or submicroscopic genetic abnormalities and identify recurrent genetic abnormalities in nondividing cells As a consequence it is commonly extrapolated that FISH will improve the sensitivity of detecting all genetic abnormalities compared with conventional karyotyping analysis This assumption has then been translated in clinical practice to having clinicians and pathologists routinely ordering both conventional karyotyping and FISH studies in patients with hematological neoplasms Depending on how comprehensive the FISH panel is the cost for this testing may be quite expensive and its additive value remains questionable
It is common practice for laboratories to use FISH panels in conjunction with karyotyping both in diagnostic specimens and during follow-up to monitor response to therapy
Multiplex FISH M-FISH represents one of the most significant developments in molecular cytogenetics of the past decade In tumor and leukemia cytogenetics two groups have been targeted by M-FISH to identify cryptic chromosome rearrangements not detectable by conventional cytogenetic studies those with an apparently normal karyotype suspected of harboring small rearrangements not detectable by conventional cytogenetics and those with a complex aberrant karyotype which are difficult to karyotype accurately due to the sheer number of aberrations
Fluorescence in situ hybridization FISH has become a reliable and rapid complementary test in targeting critical genetic events associated with diagnostics and prognosis in hematological neoplasms
In the current health care environment which increasingly focuses on value and efficiency it is critical for pathologists and clinicians to effectively navigate this environment and judiciously incorporate these high-complexity and expensive techniques into routine patient care While conventional karyotyping provides a comprehensive view of the genome FISH can detect cryptic or submicroscopic genetic abnormalities and identify recurrent genetic abnormalities in nondividing cells As a consequence it is commonly extrapolated that FISH will improve the sensitivity of detecting all genetic abnormalities compared with conventional karyotyping analysis This assumption has then been translated in clinical practice to having clinicians and pathologists routinely ordering both conventional karyotyping and FISH studies in patients with hematological neoplasms Depending on how comprehensive the FISH panel is the cost for this testing may be quite expensive and its additive value remains questionable
It is common practice for laboratories to use FISH panels in conjunction with karyotyping both in diagnostic specimens and during follow-up to monitor response to therapy
Multiplex FISH M-FISH represents one of the most significant developments in molecular cytogenetics of the past decade In tumor and leukemia cytogenetics two groups have been targeted by M-FISH to identify cryptic chromosome rearrangements not detectable by conventional cytogenetic studies those with an apparently normal karyotype suspected of harboring small rearrangements not detectable by conventional cytogenetics and those with a complex aberrant karyotype which are difficult to karyotype accurately due to the sheer number of aberrations
Detailed Description:
Neoplastic hematology is at the forefront of personalized medicine The World Health Organization WHO classification incorporates genetic data with microscopic immunophenotypic and clinical findings and categorizes hematologic neoplasms into clinically and biologically distinct categories This system guides diagnosis prognosis and therapeutic choices which has become increasingly important with emerging targeted therapies for lymphoma and leukemia However laboratory tests for hematologic neoplasms are of high complexity and are generally quite costly
The initial assessment of many hematologic neoplasms includes morphological histological immunophenotypic flow cytometric andor immunohistochemical and conventional cytogenetic studies Data obtained from cytogenetic analysis can be pathognomonic for specific leukemias in the WHO classification for example acute myeloid leukemia AML with recurrent cytogenetic abnormalities and chronic myelogenous leukemia CML and are likely to assume a greater role in defining specific categories in further classifications
Conventional cytogenetic studies have been the gold standard for more than five decades for detecting genetic alterations that are greater than 10 Mb mega base pairs in size They have paved the way in identifying specific chromosomal aberrations associated with clinically and morphologically definitive subsets of hematological neoplasms
Fluorescent in situ hybridization FISH has become a reliable and rapid complementary test in targeting critical genetic events associated with diagnostics and prognosis in hematological neoplasms FISH has addressed the issues with conventional cytogenetic studies by targeting interphase cells in addition to metaphases It has become clear that FISH studies may also be an integral component of the diagnostic evaluation particularly where the abnormality is cryptic ie not evident by conventional cytogenetic studies
Although complementary FISH testing increases the overall detection of aberrations its benefit is not uniform across all types of hematological neoplasms This is because FISH probes are restricted to the detection of only specific abnormalities and genetic alterations beyond the scope of the FISH probes would therefore be completely missed
It is common practice for laboratories to use FISH probe panels in conjunction with karyotyping both in diagnostic specimens and during follow-up to monitor response to therapy FISH is targeted toward specific abnormalities and results can be evaluated in an automated fashion on interphase nuclei allowing for examination of more cells than conventional cytogenetic studies FISH has higher analytic and in certain circumstances higher clinical sensitivity compared with conventional cytogenetic studies The usage of FISH probe panels in aiding diagnosis or in monitoring follow-up samples of hematologic neoplasms is critical
The Eastern Collaborative Oncology Group ECOG compared conventional cytogenetic studies and FISH in AML patients and found that a probe panel to detect monosomy 5deletion 5q monosomy 7deletion 7q trisomy 8 t821 t922 MLL rearrangements with various partners t1517 and inv16t1616 had a concordance between 98 and 100 On the other hand He et al study demonstrates the limited value of FISH testing in adult AML in the setting of an adequate karyotyping study
Despite of many significant technological advances made in recent years in the area of clinical genetic testing conventional cytogenetic studies and routine FISH studies remain important laboratory testing tools available for evaluating hematologic neoplasms Usually these two testing methods complement each other and often FISH serves to clarify and better define cytogenetic results Therefore there is a very strong expectation that cytogenetic and FISH results should confirm each other in spite of cases that appear to be exceptions When conflicting results occur by these two testing methods on the same specimen clinical laboratories are challenged to offer explanations based on empirical data beyond simply stating that it was or was not due to laboratory error
Multiplex FISH M-FISH represents one of the most significant developments in molecular cytogenetics of the past decade In tumor and leukemia cytogenetics two groups have been targeted by M-FISH to identify cryptic chromosome rearrangements not detectable by conventional cytogenetic studies those with an apparently normal karyotype suspected of harboring small rearrangements not detectable by conventional cytogenetics and those with a complex aberrant karyotype which are difficult to karyotype accurately due to the sheer number of aberrations
Zhang et al used spectral karyotype SKY to re-evaluate the karyotypes of AML cases reported as normal by G-banding This resulted in the identification of one case of t1119q23p13 a subtle but recognized cytogenetic abnormality and a minor clone containing monosomy for chromosome 7 in another case In a similar study Mohr et al compared SKY to conventional karyotyping in patients with AML or MDS with normal karyotypes No abnormalities were identified
With the lack of an evidence-based standardized algorithmic approach misuse and overutilization of laboratory tests are common and result in increased health care costs and patient care complexity In the current health care environment which increasingly focuses on value and efficiency it is critical for pathologists and clinicians to incorporate high-complexity and expensive techniques into routine patient care While conventional cytogenetic studies provide a comprehensive view of the genome FISH probe panel can detect cryptic or submicroscopic genetic abnormalities and identify recurrent genetic abnormalities in nondividing cells M-FISH can identify cryptic chromosome rearrangements that are not detected by conventional cytogenetic studies As a consequence it is commonly extrapolated that FISH will improve the sensitivity of detecting all genetic abnormalities compared with conventional cytogenetic studies This assumption has then been translated in clinical practice to having clinicians and pathologists routinely ordering both conventional cytogenetic studies and FISH studies in patients with hematological neoplasms Depending on how comprehensive the FISH probe panel is the cost for this testing may be quite expensive and its additive value remains questionable
The initial assessment of many hematologic neoplasms includes morphological histological immunophenotypic flow cytometric andor immunohistochemical and conventional cytogenetic studies Data obtained from cytogenetic analysis can be pathognomonic for specific leukemias in the WHO classification for example acute myeloid leukemia AML with recurrent cytogenetic abnormalities and chronic myelogenous leukemia CML and are likely to assume a greater role in defining specific categories in further classifications
Conventional cytogenetic studies have been the gold standard for more than five decades for detecting genetic alterations that are greater than 10 Mb mega base pairs in size They have paved the way in identifying specific chromosomal aberrations associated with clinically and morphologically definitive subsets of hematological neoplasms
Fluorescent in situ hybridization FISH has become a reliable and rapid complementary test in targeting critical genetic events associated with diagnostics and prognosis in hematological neoplasms FISH has addressed the issues with conventional cytogenetic studies by targeting interphase cells in addition to metaphases It has become clear that FISH studies may also be an integral component of the diagnostic evaluation particularly where the abnormality is cryptic ie not evident by conventional cytogenetic studies
Although complementary FISH testing increases the overall detection of aberrations its benefit is not uniform across all types of hematological neoplasms This is because FISH probes are restricted to the detection of only specific abnormalities and genetic alterations beyond the scope of the FISH probes would therefore be completely missed
It is common practice for laboratories to use FISH probe panels in conjunction with karyotyping both in diagnostic specimens and during follow-up to monitor response to therapy FISH is targeted toward specific abnormalities and results can be evaluated in an automated fashion on interphase nuclei allowing for examination of more cells than conventional cytogenetic studies FISH has higher analytic and in certain circumstances higher clinical sensitivity compared with conventional cytogenetic studies The usage of FISH probe panels in aiding diagnosis or in monitoring follow-up samples of hematologic neoplasms is critical
The Eastern Collaborative Oncology Group ECOG compared conventional cytogenetic studies and FISH in AML patients and found that a probe panel to detect monosomy 5deletion 5q monosomy 7deletion 7q trisomy 8 t821 t922 MLL rearrangements with various partners t1517 and inv16t1616 had a concordance between 98 and 100 On the other hand He et al study demonstrates the limited value of FISH testing in adult AML in the setting of an adequate karyotyping study
Despite of many significant technological advances made in recent years in the area of clinical genetic testing conventional cytogenetic studies and routine FISH studies remain important laboratory testing tools available for evaluating hematologic neoplasms Usually these two testing methods complement each other and often FISH serves to clarify and better define cytogenetic results Therefore there is a very strong expectation that cytogenetic and FISH results should confirm each other in spite of cases that appear to be exceptions When conflicting results occur by these two testing methods on the same specimen clinical laboratories are challenged to offer explanations based on empirical data beyond simply stating that it was or was not due to laboratory error
Multiplex FISH M-FISH represents one of the most significant developments in molecular cytogenetics of the past decade In tumor and leukemia cytogenetics two groups have been targeted by M-FISH to identify cryptic chromosome rearrangements not detectable by conventional cytogenetic studies those with an apparently normal karyotype suspected of harboring small rearrangements not detectable by conventional cytogenetics and those with a complex aberrant karyotype which are difficult to karyotype accurately due to the sheer number of aberrations
Zhang et al used spectral karyotype SKY to re-evaluate the karyotypes of AML cases reported as normal by G-banding This resulted in the identification of one case of t1119q23p13 a subtle but recognized cytogenetic abnormality and a minor clone containing monosomy for chromosome 7 in another case In a similar study Mohr et al compared SKY to conventional karyotyping in patients with AML or MDS with normal karyotypes No abnormalities were identified
With the lack of an evidence-based standardized algorithmic approach misuse and overutilization of laboratory tests are common and result in increased health care costs and patient care complexity In the current health care environment which increasingly focuses on value and efficiency it is critical for pathologists and clinicians to incorporate high-complexity and expensive techniques into routine patient care While conventional cytogenetic studies provide a comprehensive view of the genome FISH probe panel can detect cryptic or submicroscopic genetic abnormalities and identify recurrent genetic abnormalities in nondividing cells M-FISH can identify cryptic chromosome rearrangements that are not detected by conventional cytogenetic studies As a consequence it is commonly extrapolated that FISH will improve the sensitivity of detecting all genetic abnormalities compared with conventional cytogenetic studies This assumption has then been translated in clinical practice to having clinicians and pathologists routinely ordering both conventional cytogenetic studies and FISH studies in patients with hematological neoplasms Depending on how comprehensive the FISH probe panel is the cost for this testing may be quite expensive and its additive value remains questionable
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None