Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Riva, Giovanni; Nasillo, Vincenzo; Ottomano, Anna Maria; Bergonzini, Giuliano; Paolini, Ambra; Forghieri, Fabio; Lusenti, Beatrice; Barozzi, Patrizia; Lagreca, Ivana; Fiorcari, Stefania; Martinelli, Silvia; Maffei, Rossana; Marasca, Roberto; Potenza, Leonardo; Comoli, Patrizia; Manfredini, Rossella; Tagliafico, Enrico; Trenti, Tommaso; Luppi, Mario

doi:10.3390/cancers13184582

Cited by 35 publications

(39 citation statements)

References 141 publications

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“…An adequate BM or PB sample (1-2 ml) and an extensive antibody panel with backbone and lineage markers is needed is needed for MFC analysis of MRD. In addition, millions of clean CD45+ cell events should be acquired to ensure adequate LLOD and LLOQ levels ( 35 ). More recently, the International Group of Experts on Measurable Residual Disease in Hairy Cell Leukemia developed specific guidelines for evaluation of MRD in HCL (manuscript submitted).…”

Section: Methods Of Mrd Detection In Hclmentioning

confidence: 99%

Measurable residual disease in hairy cell leukemia: Technical considerations and clinical significance

Robak

2022

Front. Oncol.

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Hairy cell leukemia (HCL) is a rare type of chronic lymphoid leukemia originating from a mature B lymphocyte. A diagnosis of HCL is based on cytology, confirmed by multiparametric flow cytometry (MFC) studies using anti-B-cell monoclonal antibodies, together with a panel of antibodies more specific to HCL, such as CD11c, CD25, CD103 and CD123. Recently, the BRAF V600E mutation has been described as a disease-defining genetic event. Measurable residual disease (MRD) is defined as the lowest level of HCL cells that can be detected accurately and reproducibly using validated methods; as MRD negativity is associated with high rates of durable complete response, by clearing MRD, the long-term outcome may be improved in patients with advanced HCL. MRD is typically detected using bone marrow, and in some cases, peripheral blood; however, in HCL, discrepancies frequently exist between MRD results obtained from blood, bone marrow aspirate and core biopsy. Among the methods used for MRD detection, MFC appears to be a more sensitive technique than immunohistochemistry. Molecular tests are also used, such as real-time quantitative PCR for unique immunoglobulin heavy chain (IgH) gene rearrangements and PCR techniques with clone specificity for BRAF V600E. Clone-specific PCR (spPCR) is able to detect one HCL cell in 106 normal cells, and is particularly suitable for patients found to be negative for MRD by MFC. Recently, the Hairy Cell Leukemia Consortium created a platform to work on a definition for MRD, and establish the optimal time point, tissue type and method for measuring MRD. This

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Section: Methods Of Mrd Detection In Hclmentioning

confidence: 99%

Measurable residual disease in hairy cell leukemia: Technical considerations and clinical significance

Robak

2022

Front. Oncol.

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“…Consistent with this, the restoration of a functional anti-myeloma T cell immunity can represent an effective treatment option for advanced disease (as evidenced by CAR-T therapy in RRMM patients), and in turn, some immunological approaches could even be investigated at earlier stages (i.e., MGUS and SMM) to prevent the progression to symptomatic MM. In this view, the identification of novel specific T cell markers and the validation of significant T cell profiles may provide valuable new prognostic tools in the management of both MGUS and MM patients, possibly integrating with the emerging use of MRD, as assessed by next-generation sequencing and flow cytometry (NGS and NGF) [159]. In perspective, the prognostic monitoring of either spontaneous or therapyinduced anti-myeloma T cell responses, readily detectable in the PB or BM of MGUS/MM patients, may reasonably help guide the individualized use of adoptive T cell treatments in these settings.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

Lagreca

Riva²,

Nasillo³

et al. 2022

IJMS

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Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.

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“…The choice of MRD markers and choice of tissue to examine often varies by type of malignancy and specific clinical needs. FC is widely used in most haematological malignancies [106] and measures protein markers at the surface of individual malignant cells and often a fresh bone marrow sample is required. Immunophenotypic evaluation by multiparameter FC can detect one malignant cell in 10 3 –10 5 normal cells [107], as it uses a combination of leukaemic specific markers.…”

Section: How To Best Assess Treatment Response and Follow Longitudina...mentioning

confidence: 99%

Application of precision medicine in clinical routine in haematology—Challenges and opportunities

et al. 2022

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Precision medicine is revolutionising patient care in cancer. As more knowledge is gained about the impact of specific genetic lesions on diagnosis, prognosis and treatment response, diagnostic precision and the possibility for optimal individual treatment choice have improved. Identification of hallmark genetic aberrations such as the BCR::ABL1 gene fusion in chronic myeloid leukaemia (CML) led to the rapid development of efficient targeted therapy and molecular follow‐up, vastly improving survival for patients with CML during recent decades. The assessment of translocations, copy number changes and point mutations are crucial for the diagnosis and risk stratification of acute myeloid leukaemia and myelodysplastic syndromes. Still, the often heterogeneous and complex genetic landscape of haematological malignancies presents several challenges for the implementation of precision medicine to guide diagnosis, prognosis and treatment choice. This review provides an introduction and overview of the important molecular characteristics and methods currently applied in clinical practice to guide clinical decision making in haematological malignancies of myeloid and lymphoid origin. Further, experimental ways to guide the choice of targeted therapy for refractory patients are reviewed, such as functional precision medicine using drug profiling. An example of the use of pipeline studies where the treatment is chosen according to the molecular characteristics in rare solid malignancies is also provided. Finally, the future opportunities and remaining challenges of precision medicine in the real world are discussed.

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Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Cited by 35 publications

References 141 publications

Measurable residual disease in hairy cell leukemia: Technical considerations and clinical significance

Measurable residual disease in hairy cell leukemia: Technical considerations and clinical significance

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

Application of precision medicine in clinical routine in haematology—Challenges and opportunities

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