Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience
Abstract. Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) u...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-06-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000044 |
| _version_ | 1827334678980329472 |
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| author | Waleed Alduaij Caroline J. McNamara Andre Schuh Andrea Arruda Mahadeo Sukhai Nisha Kanwar Mariam Thomas Jay Spiegel James A. Kennedy Tracy Stockley Hubert Tsui Rebecca Devlin Hassan Sibai Dawn Maze Aaron Schimmer Karen Yee Steven Chan Suzanne Kamel-Reid Vikas Gupta |
| author_facet | Waleed Alduaij Caroline J. McNamara Andre Schuh Andrea Arruda Mahadeo Sukhai Nisha Kanwar Mariam Thomas Jay Spiegel James A. Kennedy Tracy Stockley Hubert Tsui Rebecca Devlin Hassan Sibai Dawn Maze Aaron Schimmer Karen Yee Steven Chan Suzanne Kamel-Reid Vikas Gupta |
| author_sort | Waleed Alduaij |
| collection | DOAJ |
| description | Abstract. Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) using a 54-gene NGS myeloid panel is offered to all new patients referred for myeloid malignancies, as part of a prospective observational study. Here, we evaluated the diagnostic, prognostic, and potential therapeutic utility of clinical grade TAR-SEQ in the routine workflow of 179 patients with myeloproliferative neoplasms (MPN).
Of 13 patients with triple negative (TN) MPN, who lacked driver mutations in JAK2, CALR, and MPL, TAR-SEQ confirmed clonal hematopoiesis in 8 patients. In patients with intermediate-risk myelofibrosis (MF), TAR-SEQ helped optimize clinical decisions in hematopoietic cell transplant (HCT)-eligible patients through identifying a high molecular risk (HMR) mutation profile. The presence of an HMR profile favored HCT in 9 patients with intermediate-1 risk MF. Absence of an HMR profile resulted in a delayed HCT strategy in 10 patients with intermediate-2 risk MF, 7 of which were stable at the last follow-up. Finally, TAR-SEQ identified patients with various targetable mutations in IDH1/2 (4%), spliceosome genes (28%), and EZH2 (7%). Some of these patients can be potential candidates for future targeted therapy trials.
In conclusion, we have demonstrated that TAR-SEQ improves the characterization of TN MPN, can be integrated in clinical practice as an additional tool to refine decision making in HCT, and has the potential to identify candidates for future targeted therapy trials. |
| first_indexed | 2024-03-07T18:01:11Z |
| format | Article |
| id | doaj.art-ef9dc5c3d5384ca9aa0df67a4ad0775a |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T18:01:11Z |
| publishDate | 2018-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-ef9dc5c3d5384ca9aa0df67a4ad0775a2024-03-02T10:57:27ZengWileyHemaSphere2572-92412018-06-012310.1097/HS9.0000000000000044201806000-00009Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center ExperienceWaleed AlduaijCaroline J. McNamaraAndre SchuhAndrea ArrudaMahadeo SukhaiNisha KanwarMariam ThomasJay SpiegelJames A. KennedyTracy StockleyHubert TsuiRebecca DevlinHassan SibaiDawn MazeAaron SchimmerKaren YeeSteven ChanSuzanne Kamel-ReidVikas GuptaAbstract. Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) using a 54-gene NGS myeloid panel is offered to all new patients referred for myeloid malignancies, as part of a prospective observational study. Here, we evaluated the diagnostic, prognostic, and potential therapeutic utility of clinical grade TAR-SEQ in the routine workflow of 179 patients with myeloproliferative neoplasms (MPN). Of 13 patients with triple negative (TN) MPN, who lacked driver mutations in JAK2, CALR, and MPL, TAR-SEQ confirmed clonal hematopoiesis in 8 patients. In patients with intermediate-risk myelofibrosis (MF), TAR-SEQ helped optimize clinical decisions in hematopoietic cell transplant (HCT)-eligible patients through identifying a high molecular risk (HMR) mutation profile. The presence of an HMR profile favored HCT in 9 patients with intermediate-1 risk MF. Absence of an HMR profile resulted in a delayed HCT strategy in 10 patients with intermediate-2 risk MF, 7 of which were stable at the last follow-up. Finally, TAR-SEQ identified patients with various targetable mutations in IDH1/2 (4%), spliceosome genes (28%), and EZH2 (7%). Some of these patients can be potential candidates for future targeted therapy trials. In conclusion, we have demonstrated that TAR-SEQ improves the characterization of TN MPN, can be integrated in clinical practice as an additional tool to refine decision making in HCT, and has the potential to identify candidates for future targeted therapy trials.http://journals.lww.com/10.1097/HS9.0000000000000044 |
| spellingShingle | Waleed Alduaij Caroline J. McNamara Andre Schuh Andrea Arruda Mahadeo Sukhai Nisha Kanwar Mariam Thomas Jay Spiegel James A. Kennedy Tracy Stockley Hubert Tsui Rebecca Devlin Hassan Sibai Dawn Maze Aaron Schimmer Karen Yee Steven Chan Suzanne Kamel-Reid Vikas Gupta Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience HemaSphere |
| title | Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience |
| title_full | Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience |
| title_fullStr | Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience |
| title_full_unstemmed | Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience |
| title_short | Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience |
| title_sort | clinical utility of next generation sequencing in the management of myeloproliferative neoplasms a single center experience |
| url | http://journals.lww.com/10.1097/HS9.0000000000000044 |
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