Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias

Abhishek A. Mangaonkar, Alejandro Ferrer, Filippo Pinto e Vairo, Margot A. Cousin, Ryan J. Kuisle, Naseema Gangat, William J. Hogan, Mark R. Litzow, Tammy M. McAllister, Eric W. Klee, Konstantinos N. Lazaridis, A. Keith Stewart, Mrinal M. Patnaik

Research output: Contribution to journalArticle

Abstract

Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.

Original languageEnglish (US)
JournalMayo Clinic proceedings
DOIs
StatePublished - Jan 1 2019

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Precision Medicine
Exome
Poisons
Hematopoietic Stem Cell Transplantation
Cell Lineage
Genomics
Tissue Donors

ASJC Scopus subject areas

  • Medicine(all)

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Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias. / Mangaonkar, Abhishek A.; Ferrer, Alejandro; Pinto e Vairo, Filippo; Cousin, Margot A.; Kuisle, Ryan J.; Gangat, Naseema; Hogan, William J.; Litzow, Mark R.; McAllister, Tammy M.; Klee, Eric W.; Lazaridis, Konstantinos N.; Stewart, A. Keith; Patnaik, Mrinal M.

In: Mayo Clinic proceedings, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35{\%}), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44{\%}), and patients who did not fit into the above two categories (“others,” n=14, 21{\%}). A significant family history was found in only 17 (25{\%}) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63{\%}) patients (34 [79{\%}] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25{\%}) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47{\%}), donor choice (n=6, 35{\%}), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47{\%}). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.",
author = "Mangaonkar, {Abhishek A.} and Alejandro Ferrer and {Pinto e Vairo}, Filippo and Cousin, {Margot A.} and Kuisle, {Ryan J.} and Naseema Gangat and Hogan, {William J.} and Litzow, {Mark R.} and McAllister, {Tammy M.} and Klee, {Eric W.} and Lazaridis, {Konstantinos N.} and Stewart, {A. Keith} and Patnaik, {Mrinal M.}",
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T1 - Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias

AU - Mangaonkar, Abhishek A.

AU - Ferrer, Alejandro

AU - Pinto e Vairo, Filippo

AU - Cousin, Margot A.

AU - Kuisle, Ryan J.

AU - Gangat, Naseema

AU - Hogan, William J.

AU - Litzow, Mark R.

AU - McAllister, Tammy M.

AU - Klee, Eric W.

AU - Lazaridis, Konstantinos N.

AU - Stewart, A. Keith

AU - Patnaik, Mrinal M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.

AB - Objective: To demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes. Patients and Methods: Patients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists. Results: Sixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%). Conclusion: We show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.

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