Correlation between a 10‐color flow cytometric measurable residual disease ( MRD ) analysis and molecular MRD in adult B‐acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Jasmine Singh ◽  
Malgorzata Gorniak ◽  
George Grigoriadis ◽  
David Westerman ◽  
Michelle McBean ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Color Flow ◽  
Flow Cytometric ◽  
Measurable Residual Disease

Use of Four-Color Flow Cytometric Assay for Discrimination of Hematogone from Lymphoblast: Critical Issue for MRD Assessment in B-ALL Patients

2020 ◽  
Author(s):  
Mehdi Allahbakhshian Farsani ◽  
Esmaeil Shahabi Satlsar ◽  
Alireza Mohseni ◽  
Mohammad Mosleh ◽  
Mahdieh Mehrpouri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Critical Issue ◽  
Color Flow ◽  
Flow Cytometric ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Cells

Background: Hematogones are normal B-cell precursor which can be seen in different physiological and pathological conditions. Due to variation in B-cell acute lymphoblastic leukemia (B-ALL) blasts immunophenotyping and interference of hematogones in minimal residual disease (MRD) assessment, precise discrimination of hematogones is very crucial.  The purpose of this study was to evaluate the expression pattern of surface markers in hematogones and compare them with lymphoblasts. Material and Methods: In this applied study, flow cytometric analysis was performed using Coulter FC-500 and MXP software in 4-color combination and 6 different tubes. In this study, 85 patients diagnosed with acute lymphoblastic leukemia were evaluated. Out of these patients, 45 were boys and 40 were girls. Patients aged from 1 to 15 years old. In addition, 27 bone marrow samples from other patients aged 4 to 18 years were included in this investigation. These samples had been obtained for other diagnostic purposes, such as immune thrombocytopenic purpura and juvenile idiopathic arthritis. Results: During flow cytometric analysis, hematogones showed expressions of CD19, CD20, CD22, CD10, CD45, CD81, CD123, CD9, CD34 (partial expression), and tdt (partial expression). In these patients, hematgones were negative for CD66c expression. Lymphoblastic cells were positive for CD19, CD20 (in some cases), CD22, CD10, CD45, CD81, CD123, CD58, CD9, CD66c, CD34 (in most cases), and TDT. CD81 mean fluorescence intensity (MFI) in hematogones was higher than that in lymphoblasts. (112.5 (30-251) vs. 17.5 (5-30); P<0.0001) Conclusion: According to findings of this study, it seems that the use of CD81, CD58, CD123, CD66c, CD9, and CD81 MFI in combination with B-Cells associated markers can be very effective in differentiating hematogone from lymphoblast.

scholarly journals Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia

2020 ◽  
Vol 4 (14) ◽  
pp. 3239-3245
Author(s):  
Ryan D. Cassaday ◽  
Kelsey-Leigh A. Garcia ◽  
Jonathan R. Fromm ◽  
Mary-Elizabeth M. Percival ◽  
Cameron J. Turtle ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Stevens Johnson Syndrome ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Measurable Residual Disease

Abstract The presence of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) confers a poor prognosis. CD19-targeted immunotherapy is effective against MRD but is logistically challenging, potentially toxic, and not applicable to T-cell ALL. We thus hypothesized that inhibition of PD-1 with pembrolizumab could also be effective for MRD, but without lineage restriction. The primary objective of this phase 2 study was to evaluate the efficacy of pembrolizumab in patients with ALL and MRD. Key eligibility criteria included adults with B- or T-cell ALL and MRD detectable by multiparameter flow cytometry or quantitative polymerase chain reaction from bone marrow aspirate (BMA) despite chemotherapy (plus ABL kinase inhibitor if Philadelphia chromosome positive). Pembrolizumab 200 mg IV was given every 3 weeks. Response was assessed by BMA using methods that previously detected MRD. The primary end point was complete MRD response rate. We stopped enrollment early; only 1 of 12 (8%) experienced a complete MRD response, which lasted 3 weeks. Interestingly, this patient had previously received hematopoietic cell transplantation and CD19-targeted chimeric antigen receptor–modified T-cell therapy and was the only patient to experience an immune-related adverse event from pembrolizumab (grade 3 Stevens-Johnson syndrome). Median overall survival from enrollment was 12.7 months. In summary, pembrolizumab had minimal activity against MRD but was generally well tolerated. These data can be compared with ongoing anti-PD-1 combination studies in ALL, and they further establish the role of trials specifically for patients with MRD. This trial was registered at www.clinicaltrials.gov as #NCT02767934.

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