Deep Sequencing Reveals Myeloma Cells in Peripheral Blood in Majority of Multiple Myeloma Patients

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• 作者：Ravi Vij¹ ; Amitabha Mazumder² ; Mark Klinger³ ; Denise O'Dea² ; Jacob Paasch¹ ; Thomas Martin⁴ ; Li Weng³ ; Jeesun Park² ; Mark Fiala¹ ; Malek Faham³ ; Jeffrey Wolf⁴ ; ^{wolfj@medicine.ucsf.edu" class="auth_mail}
• 关键词：Circulating myeloma clones ; High-throughput sequencing ; Immunoglobulin gene rearrangement ; Minimal residual disease ; Multiple myeloma
• 刊名：Clinical Lymphoma Myeloma and Leukemia
• 出版年：April, 2014
• 年：2014
• 卷：14
• 期：2
• 页码：131-139.e1
• 全文大小：1111 K

文摘

Introduction

The evaluation of myeloma cells in multiple myeloma (MM) patients has generally been limited to the assessment of bone marrow involvement because of the sensitivity limitations of traditional minimal-residual-disease-detection methods.

Materials and Methods

We developed a sequencing-based method to identify myeloma cells in bone marrow (BM) and peripheral blood (PB) samples, based on their unique immunoglobulin gene rearrangements, that can detect cancer clones at levels well below 1 in 1 million leukocytes (0.0001%). In this multisite study, we used this sequencing method to determine the fraction of patients with myeloma cells in their PB at diagnosis and posttreatment time points.

Results

Using this sequencing approach, we detected myeloma cells in the PB in the vast majority of MM patients (44/46, 96%). We demonstrated a clear correlation (R²聽= 0.57) between myeloma clone levels in paired BM and PB samples, and noted that PB clone levels were approximately 100-fold lower than levels in BM samples. The sequencing assay demonstrated a clear sensitivity advantage in the BM compartment and at least equivalent sensitivity in the PB compared with that of monoclonal-protein results.

Conclusion

This study highlights the promise of a blood-based, sequencing minimal-residual-disease assay that can be used to measure MM disease burden at different time points and various disease stages.