scholarly journals Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry

2017 ◽  
Vol 37 (4) ◽  
pp. 821-853 ◽  
Author(s):  
Kah Teong Soh ◽  
Joseph D. Tario ◽  
Paul K. Wallace
2020 ◽  
Vol 4 (5) ◽  
pp. 880-884 ◽  
Author(s):  
Andrew Staron ◽  
Eric J. Burks ◽  
John C. Lee ◽  
Shayna Sarosiek ◽  
J. Mark Sloan ◽  
...  

Abstract Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede organ response in some patients. Assessment of minimal residual disease (MRD) may therefore have clinical importance as a more stringent treatment response tool for patients in a hematologic complete response. We used 2-tube, 10-color combination multiparametric flow cytometry to assess for MRD at a minimum sensitivity of 1 in 105 nucleated cells. Of 65 patients in hematologic complete response, 36 (55%) were found to have a residual clonal plasma cell population in the bone marrow. Comparing the MRD-negative and MRD-positive groups, renal response was observed in 88% vs 64% (P = .06), cardiac response in 75% vs 59% (P = .45), and any organ response in 90% vs 75% (P = .20) of patients. Depth of organ response as measured by the percent decrease in 24-hour proteinuria and brain natriuretic peptide was 96% vs 91% (P = .16) and 55% vs 46% (P = .66), respectively. These data suggest a possible correlation between MRD negativity and higher probability of organ response after treatment in AL amyloidosis. Future prospective studies with a larger cohort are needed to determine the clinical relevance of these improvements. This trial was registered at www.clinicaltrials.gov as #NCT00898235.


2015 ◽  
Vol 139 (10) ◽  
pp. 1276-1280 ◽  
Author(s):  
Michael Keeney ◽  
Jaimie G. Halley ◽  
Daniel D. Rhoads ◽  
M. Qasim Ansari ◽  
Steven J. Kussick ◽  
...  

Context Flow cytometry is often applied to minimal residual disease (MRD) testing in hematolymphoid neoplasia. Because flow-based MRD tests are developed in the laboratory, testing methodologies and lower levels of detection (LODs) are laboratory dependent. Objectives To broadly survey flow cytometry laboratories about MRD testing in laboratories, if performed, including indications and reported LODs. Design Voluntary supplemental questions were sent to the 549 laboratories participating in the College of American Pathologists (CAP) FL3-A Survey (Flow Cytometry—Immunophenotypic Characterization of Leukemia/Lymphoma) in the spring of 2014. Results A total of 500 laboratories (91%) responded to the supplemental questions as part of the FL3-A Survey by April 2014; of those 500 laboratories, 167 (33%) currently perform MRD for lymphoblastic leukemia, 118 (24%) for myeloid leukemia, 99 (20%) for chronic lymphocytic leukemia, and 91 (18%) for plasma cell myeloma. Other indications include non-Hodgkin lymphoma, hairy cell leukemia, neuroblastoma, and myelodysplastic syndrome. Most responding laboratories that perform MRD for lymphoblastic leukemia reported an LOD of 0.01%. For myeloid leukemia, chronic lymphocytic leukemia, and plasma cell myeloma, most laboratories indicated an LOD of 0.1%. Less than 3% (15 of 500) of laboratories reported LODs of 0.001% for one or more MRD assays performed. Conclusions There is major heterogeneity in the reported LODs of MRD testing performed by laboratories subscribing to the CAP FL3-A Survey. To address that heterogeneity, changes to the Flow Cytometry Checklist for the CAP Laboratory Accreditation Program are suggested that will include new requirements that each laboratory (1) document how an MRD assay's LOD is measured, and (2) include the LOD or lower limit of enumeration for flow-based MRD assays in the final diagnostic report.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5261-5261
Author(s):  
Fen Huang ◽  
Hui Jing ◽  
Zhengshan Yi ◽  
Xiaolei Wei ◽  
Zhongxin Zheng ◽  
...  

Abstract Purpose Minimal residual disease (MRD) detected by multiparametric flow cytometry is an important method for predicting relapse. According to the dynamic changes of MRD, through the first clinical treatment to prevent relapse in patients with elevated MRD levels. Method We retrospectively analyze dynamic level of MRD of 75 patients with acute leukemia in our department of hematology from January 2011 to June 2013. According to the retrospective data, to analyze the expression of LAIP and discuss the relationship between changes of MRD and prognosis. Result In this study there were 75 patients, including 20 patients with acute lymphocytic leukemia (ALL) and 55 patients with acute myeloid leukemia (AML). The specific LAIP were detected in 49 patients with AML, and the cross lineage and non-synchronous expression were majority. In cross lineage expression, detected frequency of CD45/CD34/CD33/CD13/CD56 was highest, accounted for 67.3% (33/49). In non-synchronous expression, CD45/CD34/CD117/CD33/CD64 accounted for 57.1% (28/49). In 20 patients with ALL, there were 16 patients with B-ALL and 4 patients with T-ALL. The specific LAIP were detected in all of the patients. In patients with B-ALL, detected frequency of CD45/CD19/CD22/CD10/CD13 was highest, accounting for 43.8% (7/16). In abnormal quantity of antigens, CD45/CD19/CD22/CD10/CD38 was the most common type, accounting for 50%. The abnormal expression of CD7/TDT was detected in four patients with T-ALL. In monitoring period 7 patients relapsed. We analyzed the relationship between the clinical data and replase. The results showed that level of peripheral hemoglobin at diagnosis and the times of remission induction were significantly associated with replase (P=0.021 and P=0.017, respectively). To analyze the relationship between change of MRD and prognosis, the results showed that 0.05% as the threshold was significantly related with recurrence. 20 patients of persistent MRD≥0.05% had significant differences with 28 patients of persistent MRD<0.05% in replase free survival (P=0.005). Conclusion It has important significance to predict relapse in patients with acute leukemia by detecting minimal residual disease. Patients of MRD ≥ 0.05% should receive early intensive therapy or hematopoietic stem cell transplantation. Even patients without relapse, it should be closely monitor dynamic levels of MRD and highly vigilant extramedullary relapse. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5036-5036
Author(s):  
Tove Isaacson ◽  
Andrzej Jakubowiak ◽  
Lloyd Stoolman ◽  
Usha Kota ◽  
William Finn ◽  
...  

Abstract Multiparameter flow cytometry is a useful tool for comprehensive immunophenotyping of plasma cell myeloma, and has been proposed as a sensitive method for the evaluation of minimal residual disease in patients following treatment. This study aimed to assess the value of flow cytometry in quantitation of residual disease, in comparison to routine morphologic examination of first-pull bone marrow aspirate smears, in myeloma patients post-therapy. Heparinized bone marrow aspirates were obtained from 27 treated patients with plasma cell myeloma. Cells were prepared for 5-color flow cytometric analysis within 24-hours of specimen draw. Surface membrane staining with anti-CD19, CD20, CD38, CD45, CD56, and CD138 was followed by ammonium chloride lysis of red cells. Fixed and permeabilized cells were analyzed for cytoplasmic light chains to confirm clonality. Data were acquired using an FC500 flow cytometer (Beckman-Coulter), analyzed with CXP software with plasma cells isolated based on bright CD38+ or CD138+ expression. A median of 97,639 cellular events (range 14,279 to 262,508) were collected per analysis. Flow cytometric enumeration of plasma cells was compared to 500-cell differential counts of Wright-Giemsa-stained first-pull aspirate smears from the same cases. The median plasma cell count as determined by flow cytometry was 0.5% (range 0–7.9%). The median plasma cell count estimated by morphologic review was 8.0% (range 0–84.4%). Flow cytometry underestimated the plasma cell content in all but one case. Clonal plasma cells expressed CD38 and CD138 in all cases; 87.5% (21/24) coexpressed CD56, 25% (6/24) coexpressed CD45, and 4.2% (1/24) coexpressed CD19. None was positive for CD20. Although detection of minimal residual disease after therapy for acute leukemia is routinely achieved by flow cytometric analysis, successful quantitation of minimal residual disease in treated myeloma patients using flow cytometry remains limited as it usually underestimates the plasma cell content of bone marrow samples compared to routine morphology of first-pull aspirates. We have observed that this holds true for both pre-treatment and post-treatment specimens. Causes for the discrepancy may include hemodilution of second-pull aspirates used for flow cytometry, fragility and loss of plasma cells during preparation for flow cytometry, and incomplete disaggregation of plasma cells from bone marrow spicules. With improved outcome of treatments, better and more reliable methods of detection of minimal residual disease are needed for optimal prognostic stratification. We are currently validating alternative methods, which may offer more sensitivity while at the same time allow more objectivity, for assessing the amount of minimal residual disease in myeloma patients.


2017 ◽  
Vol 30 (Suppl 2) ◽  
pp. 2S21-2S28
Author(s):  
Lucie Říhová ◽  
Pavla Všianská ◽  
Renata Bezděková ◽  
Romana Králová ◽  
Miroslav Penka ◽  
...  

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