Comparison of Diagnostic Yield Among M-FISH, FISH Probe Panel and Conventional Cytogenetic Analysis in AML

NCT03719183 | Completed DMC

• 1 other identifier: AssiutU-SECI-Cytogenetic 100
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

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).

Conditions

Acute Myeloid Leukemia

Keywords

M-FISH, FISH, AML

Outcome Measures

Primary Outcomes (2)

• Evaluation of cytogenetic profile of AML patients in South Egypt

  Study the hematological and cytogenetic profile of AML patients in a tertiary center in Egypt

  2 years

• Comparing Diagnostic Yield among Multiplex Fluorescent in situ hybridization, fluorescent in situ hybridization probe panel and conventional cytogenetic analysis in newly diagnosed patients with AML.

  Compare M-FISH, karyotyping and FISH probe panel in AML patients in a limited resource institute

  2 years

Secondary Outcomes (1)

• Correlation between cytogenetic results and demographic, clinical and hematological data of AML patients

  2 years

Study Arms (1)

Acute Myeloid Leukemia (AML) group

Patients who are diagnosed as Acute Myeloid Leukemia based on peripheral blood, bone marrow aspiration and immunophenotyping and fulfill WHO criteria for diagnosis. Fluorescent in Situ Hybridization (FISH) Panels for AML, Multiplex FISH (M-FISH) and Conventional Cytogenetics Studies will be performed for AML patients.

Diagnostic Test: Conventional Cytogenetics Studies; Diagnostic Test: Fluorescent in Situ Hybridization (FISH) Panels; Diagnostic Test: Multiplex FISH (M-FISH)

Interventions

Conventional Cytogenetics Studies DIAGNOSTIC_TEST

Metaphase cytogenetic studies will be performed in all cases according to standard methods. Chromosome preparations will be G-banded using trypsin and Giemsa, and karyotypes will be described according to the International System for Human Cytogenetic Nomenclature (ISCN) 2016.

Also known as: Karyotyping

Acute Myeloid Leukemia (AML) group

Fluorescent in Situ Hybridization (FISH) Panels DIAGNOSTIC_TEST

AML Panel includes: * t(8;21) (RUNX1-RUNX1T1). * inv(16), t(16;16) (CBFB-MYH11). * t(9;22) (BCR-ABL). * 11q23 KMT2A rearrangements. * inv(3) MECOM rearrangements. * DEK-NUP214 rearrangements. * Del(5q) Deletion * Del(7q) Deletion Acute Promyelocytic Leukemia panel includes: * t(15;17) (PML-RARA). * 17q RARA rearrangements

Acute Myeloid Leukemia (AML) group

Multiplex FISH (M-FISH) DIAGNOSTIC_TEST

24-color karyotyping

Acute Myeloid Leukemia (AML) group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed AML patients.

You may qualify if:

• Patients with newly diagnosed acute myeloid leukemia.
• Age group: patients more than 18 years old.

You may not qualify if:

• Patients less than 18 years old.
• Patients with other types of hematologic neoplasms.
• Relapsed patients.

Sponsors & Collaborators

• Assiut University: lead
• South Egypt Cancer Institute: collaborator

Study Sites (1)

South Egypt Cancer Institute

Asyut, 71515, Egypt

Location

Related Publications (12)

• Ashok V, Ranganathan R, Chander S, Damodar S, Bhat S, S NK, A SK, Jadav SS, Rajashekaraiah M, T S S. Comparison of Diagnostic Yield of a FISH Panel Against Conventional Cytogenetic Studies for Hematological Malignancies: A South Indian Referral Laboratory Analysis Of 201 Cases. Asian Pac J Cancer Prev. 2017 Dec 29;18(12):3457-3464. doi: 10.22034/APJCP.2017.18.12.3457.

  PMID: 29286619 BACKGROUND

• Cantu ES, Dong H, Forsyth DR, Espinoza FP, Papenhausen PR. Discrepant Cytogenetic and Interphase Fluorescence In Situ Hybridization (I-FISH) Results from Bone Marrow Specimens of Patients with Hematologic Neoplasms. Ann Clin Lab Sci. 2018 May;48(3):264-272.

  PMID: 29970427 BACKGROUND

• He R, Wiktor AE, Hanson CA, Ketterling RP, Kurtin PJ, Van Dyke DL, Litzow MR, Howard MT, Reichard KK. Conventional karyotyping and fluorescence in situ hybridization: an effective utilization strategy in diagnostic adult acute myeloid leukemia. Am J Clin Pathol. 2015 Jun;143(6):873-8. doi: 10.1309/AJCPP6LVMQG4LNCK.

  PMID: 25972330 BACKGROUND

• Kearney L. Multiplex-FISH (M-FISH): technique, developments and applications. Cytogenet Genome Res. 2006;114(3-4):189-98. doi: 10.1159/000094202.

  PMID: 16954655 BACKGROUND

• Kokate P, Dalvi R, Koppaka N, Mandava S. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics. Cancer Genet. 2017 Oct;216-217:120-127. doi: 10.1016/j.cancergen.2017.05.004. Epub 2017 Aug 16.

  PMID: 29025586 BACKGROUND

• Mohr B, Bornhauser M, Thiede C, Schakel U, Schaich M, Illmer T, Pascheberg U, Ehninger G. Comparison of spectral karyotyping and conventional cytogenetics in 39 patients with acute myeloid leukemia and myelodysplastic syndrome. Leukemia. 2000 Jun;14(6):1031-8. doi: 10.1038/sj.leu.2401775.

  PMID: 10865969 BACKGROUND

• Peterson JF, Aggarwal N, Smith CA, Gollin SM, Surti U, Rajkovic A, Swerdlow SH, Yatsenko SA. Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing? Oncotarget. 2015 Aug 7;6(22):18845-62. doi: 10.18632/oncotarget.4586.

  PMID: 26299921 BACKGROUND

• Sreekantaiah C. FISH panels for hematologic malignancies. Cytogenet Genome Res. 2007;118(2-4):284-96. doi: 10.1159/000108312.

  PMID: 18000382 BACKGROUND

• Vance GH, Kim H, Hicks GA, Cherry AM, Higgins R, Hulshizer RL, Tallman MS, Fernandez HF, Dewald GW. Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900). Leuk Res. 2007 May;31(5):605-9. doi: 10.1016/j.leukres.2006.07.026. Epub 2006 Sep 22.

  PMID: 16996130 BACKGROUND

• Wheeler FC, Kim AS, Mosse CA, Shaver AC, Yenamandra A, Seegmiller AC. Limited Utility of Fluorescence In Situ Hybridization for Recurrent Abnormalities in Acute Myeloid Leukemia at Diagnosis and Follow-up. Am J Clin Pathol. 2018 Mar 29;149(5):418-424. doi: 10.1093/ajcp/aqy002.

  PMID: 29538617 BACKGROUND

• Wolff DJ, Bagg A, Cooley LD, Dewald GW, Hirsch BA, Jacky PB, Rao KW, Rao PN; Association for Molecular Pathology Clinical Practice Committee; American College of Medical Genetics Laboratory Quality Assurance Committee. Guidance for fluorescence in situ hybridization testing in hematologic disorders. J Mol Diagn. 2007 Apr;9(2):134-43. doi: 10.2353/jmoldx.2007.060128.

  PMID: 17384204 BACKGROUND

• Zhang FF, Murata-Collins JL, Gaytan P, Forman SJ, Kopecky KJ, Willman CL, Appelbaum FR, Slovak ML. Twenty-four-color spectral karyotyping reveals chromosome aberrations in cytogenetically normal acute myeloid leukemia. Genes Chromosomes Cancer. 2000 Jul;28(3):318-28. doi: 10.1002/1098-2264(200007)28:33.0.co;2-m.

  PMID: 10862038 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood or Bone marrow aspiration samples

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Karyotyping; In Situ Hybridization; In Situ Hybridization, Fluorescence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytogenetic Analysis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization

Study Officials

• Eman Mosaad, MD

  South Egypt Cancer Institute

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 25, 2018
• Study Start: January 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 9, 2022

Record last verified: 2022-03

Locations

EG (1)