ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL
General Information: A “positive” or “negative” MRD test result indicates whether measurable disease is detected above certain thresholds that may vary by test and laboratory. It is important to recognize that a negative MRD result does not necessarily indicate eradication of disease, but rather rep...
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Elsevier
2024-12-01
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| Series: | Hematology, Transfusion and Cell Therapy |
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| author | Mehmet Bakırtaş |
| author_facet | Mehmet Bakırtaş |
| author_sort | Mehmet Bakırtaş |
| collection | DOAJ |
| description | General Information: A “positive” or “negative” MRD test result indicates whether measurable disease is detected above certain thresholds that may vary by test and laboratory. It is important to recognize that a negative MRD result does not necessarily indicate eradication of disease, but rather represents disease below the test threshold in the tested sample, and patients may still experience relapse. MRD Methods: ELN identifies multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR) among useful methods suitable for detecting MRD. Recently, innovative techniques such as digital PCR (dPCR), next-generation sequencing (NGS), and next-generation flow cytometry (NGF) have also been applied in the detection of MRD. MRD in ALL: In the study by Yilmaz et al., it was seen that earlier MRD negativity in Ph(-) B-ALL was associated with higher survival. The best results were obtained with Flow Cytometry MRD negativity after the 1st cycle (i.e. CR time). The 3-year relapse rate in early MRD negativity was still approximately 25%.Short NJ et al investigated the effect of CMR in Ph (+) B ALL. In 85 Ph+ ALL patients who were treated with Hyper-CVAD plus TKI and did not undergo HSCT in CR1, the median OS was 127 months in the group achieving CMR; OS was 38 months in those without CMR (P=0.009). CMR at 3 months was seen as the only prognostic factor for OS. In the study by Sasaki K et al. evaluating the effect of TKI selection on achieving 3-month CMR; 84 Ph+ ALL patients were treated with Hyper-CVAD plus TKI and CMR was achieved at 3 months. 5-year OS was found to be 84% with ponatinib. 5-year OS was found to be 60-65% with other TKIs. Ponatinib treatment was the only prognostic factor for PFS or OS. Ghobadi A et al found no benefit from allogeneic SCT in patients with Ph+ ALL who achieved CMR.Short NJ et al. compared the correlation and prognostic impact of NGS MRD and MFC MRD in Ph(-) ALL. NGS MRD (-) 5-year OS: 90%; NGS MRD (+) 5-year OS: 61%; MFC MRD (-) NGS MRD (+) 5-year OS: 62% were seen. 46% of the MFC MRD (-) group was NGS MRD (+).Blinatumomab for MRD in B-Cell ALL showed MRD negativity rate = 78% after 1 cycle in BLAST Study.Pulsipher MA et al viewed pretransplantation NGS MRD status as prognostic in pediatric ALL. Prospective follow-up for posttransplantation MRD was superior with NGS. Liang EC et al assessed NGS MRD up to 1 year after SCT for 139 patients after allogeneic SCT.Muffly L et al evaluated the correlation of NGS MRD with Peripheral Blood and Bone Marrow. Strong correlation (r=0.87; P<0.0001) was seen between PB and BM NGS MRD. MRD was detected in PB in 100% of those who relapsed after SCT and in 85% of those who relapsed after CAR T.Pulsipher MA et al. study, MRD assessment after CAR T Cell for ALL was considered prognostic. NGS-detectable MRD after tisagenlecleucel was independently predictive of EFS and OS in multivariate analysis.Short NJ et al evaluated the effect of NGS MRD for IG/TR in Ph+ ALL. The study enrolled adults with Ph+ ALL receiving first-line therapy. Disagreements between MRD assessment by PCR and MRD assessment by NGS are relatively common. RT-PCR for BCR::ABL1 is not prognostic in patients who achieve NGS MRD negativity. Ph+ ALL patients who achieve NGS MRD negativity have good outcomes regardless of PCR response.Flow cytometry in T-ALL has been validated in T ALL, including ETP. Good agreement between bone marrow and peripheral blood. NGS has not been validated in T ALL because the cells have not yet undergone a TCR rearrangement. MRD Follow-up Periods: In first-line ALL, MRD from bone marrow should be measured after the end of induction, during early consolidation (after approximately 3 months of therapy), and then approximately every 3 months for at least 3 years (5 years for patients with Ph-positive ALL in first remission who do not undergo HSCT). In patients undergoing HSCT, MRD should be assessed immediately before HSCT; serial MRD measurements should be performed after HSCT (approximately every 3 months).” |
| format | Article |
| id | doaj-art-598ae367a89a4147a0d36bb9a722ed5b |
| institution | OA Journals |
| issn | 2531-1379 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj-art-598ae367a89a4147a0d36bb9a722ed5b2025-08-20T02:35:32ZengElsevierHematology, Transfusion and Cell Therapy2531-13792024-12-0146S1610.1016/j.htct.2024.11.111ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALLMehmet Bakırtaş0Republic of Turkey Ministry of Health, Dr. İsmail Fehmi Cumalıoğlu City Hospital, Hematology ClinicGeneral Information: A “positive” or “negative” MRD test result indicates whether measurable disease is detected above certain thresholds that may vary by test and laboratory. It is important to recognize that a negative MRD result does not necessarily indicate eradication of disease, but rather represents disease below the test threshold in the tested sample, and patients may still experience relapse. MRD Methods: ELN identifies multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR) among useful methods suitable for detecting MRD. Recently, innovative techniques such as digital PCR (dPCR), next-generation sequencing (NGS), and next-generation flow cytometry (NGF) have also been applied in the detection of MRD. MRD in ALL: In the study by Yilmaz et al., it was seen that earlier MRD negativity in Ph(-) B-ALL was associated with higher survival. The best results were obtained with Flow Cytometry MRD negativity after the 1st cycle (i.e. CR time). The 3-year relapse rate in early MRD negativity was still approximately 25%.Short NJ et al investigated the effect of CMR in Ph (+) B ALL. In 85 Ph+ ALL patients who were treated with Hyper-CVAD plus TKI and did not undergo HSCT in CR1, the median OS was 127 months in the group achieving CMR; OS was 38 months in those without CMR (P=0.009). CMR at 3 months was seen as the only prognostic factor for OS. In the study by Sasaki K et al. evaluating the effect of TKI selection on achieving 3-month CMR; 84 Ph+ ALL patients were treated with Hyper-CVAD plus TKI and CMR was achieved at 3 months. 5-year OS was found to be 84% with ponatinib. 5-year OS was found to be 60-65% with other TKIs. Ponatinib treatment was the only prognostic factor for PFS or OS. Ghobadi A et al found no benefit from allogeneic SCT in patients with Ph+ ALL who achieved CMR.Short NJ et al. compared the correlation and prognostic impact of NGS MRD and MFC MRD in Ph(-) ALL. NGS MRD (-) 5-year OS: 90%; NGS MRD (+) 5-year OS: 61%; MFC MRD (-) NGS MRD (+) 5-year OS: 62% were seen. 46% of the MFC MRD (-) group was NGS MRD (+).Blinatumomab for MRD in B-Cell ALL showed MRD negativity rate = 78% after 1 cycle in BLAST Study.Pulsipher MA et al viewed pretransplantation NGS MRD status as prognostic in pediatric ALL. Prospective follow-up for posttransplantation MRD was superior with NGS. Liang EC et al assessed NGS MRD up to 1 year after SCT for 139 patients after allogeneic SCT.Muffly L et al evaluated the correlation of NGS MRD with Peripheral Blood and Bone Marrow. Strong correlation (r=0.87; P<0.0001) was seen between PB and BM NGS MRD. MRD was detected in PB in 100% of those who relapsed after SCT and in 85% of those who relapsed after CAR T.Pulsipher MA et al. study, MRD assessment after CAR T Cell for ALL was considered prognostic. NGS-detectable MRD after tisagenlecleucel was independently predictive of EFS and OS in multivariate analysis.Short NJ et al evaluated the effect of NGS MRD for IG/TR in Ph+ ALL. The study enrolled adults with Ph+ ALL receiving first-line therapy. Disagreements between MRD assessment by PCR and MRD assessment by NGS are relatively common. RT-PCR for BCR::ABL1 is not prognostic in patients who achieve NGS MRD negativity. Ph+ ALL patients who achieve NGS MRD negativity have good outcomes regardless of PCR response.Flow cytometry in T-ALL has been validated in T ALL, including ETP. Good agreement between bone marrow and peripheral blood. NGS has not been validated in T ALL because the cells have not yet undergone a TCR rearrangement. MRD Follow-up Periods: In first-line ALL, MRD from bone marrow should be measured after the end of induction, during early consolidation (after approximately 3 months of therapy), and then approximately every 3 months for at least 3 years (5 years for patients with Ph-positive ALL in first remission who do not undergo HSCT). In patients undergoing HSCT, MRD should be assessed immediately before HSCT; serial MRD measurements should be performed after HSCT (approximately every 3 months).”http://www.sciencedirect.com/science/article/pii/S2531137924029547 |
| spellingShingle | Mehmet Bakırtaş ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL Hematology, Transfusion and Cell Therapy |
| title | ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL |
| title_full | ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL |
| title_fullStr | ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL |
| title_full_unstemmed | ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL |
| title_short | ADVANCES IN THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE (MRD) IN ALL |
| title_sort | advances in the assessment of minimal residual disease mrd in all |
| url | http://www.sciencedirect.com/science/article/pii/S2531137924029547 |
| work_keys_str_mv | AT mehmetbakırtas advancesintheassessmentofminimalresidualdiseasemrdinall |