Ying-Jung Huang1, Elaine Coustan-Smith2, Hsiao-Wen Kao3, Hsi-Che Liu4, Shih-Hsiang Chen5, Chih-Cheng Hsiao6, Chao-Ping Yang7, Tang-Her Jaing5, Ting-Chi Yeh4, Ming-Chung Kuo3, Chang-Liang Lai1, Chia-Hui Chang1, Dario Campana2, Der-Cherng Liang8, Lee-Yung Shih9. 1. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. 2. Department of Pediatrics, National University of Singapore, Singapore. 3. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. 4. Department of Pediatrics, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. 5. College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Hematology-Oncology, Chang Gung Children's Hospital at Linkou, Toayuan, Taiwan. 6. College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan. 7. Department of Hematology-Oncology, Chang Gung Children's Hospital at Linkou, Toayuan, Taiwan. 8. Department of Pediatrics, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. Electronic address: dcliang@mmh.org.tw. 9. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: sly7012@adm.cgmh.org.tw.
Abstract
BACKGROUND/ PURPOSE: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry. RESULTS: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively. CONCLUSION: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.
BACKGROUND/ PURPOSE: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemiapatients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry. RESULTS: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively. CONCLUSION: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.