AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML
Measurable residual disease (MRD) in AML, assessed by multicolor flow cytometry, is an important prognostic factor. Progenitors are key populations in defining MRD, and cases of MRD involving these progenitors are calculated as percentage of WBC and referred to as white blood cell MRD (WBC-MRD). Two...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/11/2597 |
| _version_ | 1797532697193611264 |
|---|---|
| author | Diana Hanekamp Jesse M. Tettero Gert J. Ossenkoppele Angèle Kelder Jacqueline Cloos Gerrit Jan Schuurhuis |
| author_facet | Diana Hanekamp Jesse M. Tettero Gert J. Ossenkoppele Angèle Kelder Jacqueline Cloos Gerrit Jan Schuurhuis |
| author_sort | Diana Hanekamp |
| collection | DOAJ |
| description | Measurable residual disease (MRD) in AML, assessed by multicolor flow cytometry, is an important prognostic factor. Progenitors are key populations in defining MRD, and cases of MRD involving these progenitors are calculated as percentage of WBC and referred to as white blood cell MRD (WBC-MRD). Two main compartments of WBC-MRD can be defined: (1) the AML part of the total primitive/progenitor (CD34+, CD117+, CD133+) compartment (referred to as primitive marker MRD; PM-MRD) and (2) the total progenitor compartment (% of WBC, referred to as PM%), which is the main quantitative determinant of WBC-MRD. Both are related as follows: WBC-MRD = PM-MRD × PM%. We explored the relative contribution of each parameter to the prognostic impact. In the HOVON/SAKK study H102 (300 patients), based on two objectively assessed cut-off points (2.34% and 10%), PM-MRD was found to offer an independent prognostic parameter that was able to identify three patient groups with different prognoses with larger discriminative power than WBC-MRD. In line with this, the PM% parameter itself showed no prognostic impact, implying that the prognostic impact of WBC-MRD results from the PM-MRD parameter it contains. Moreover, the presence of the PM% parameter in WBC-MRD may cause WBC-MRD false positivity and WBC-MRD false negativity. For the latter, at present, it is clinically relevant that PM-MRD ≥ 10% identifies a patient sub-group with a poor prognosis that is currently classified as good prognosis MRD<sup>negative</sup> using the European LeukemiaNet 0.1% consensus MRD cut-off value. These observations suggest that residual disease analysis using PM-MRD should be conducted. |
| first_indexed | 2024-03-10T11:02:59Z |
| format | Article |
| id | doaj.art-f67b4200403747439013fbe920609f41 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:02:59Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f67b4200403747439013fbe920609f412023-11-21T21:23:42ZengMDPI AGCancers2072-66942021-05-011311259710.3390/cancers13112597AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AMLDiana Hanekamp0Jesse M. Tettero1Gert J. Ossenkoppele2Angèle Kelder3Jacqueline Cloos4Gerrit Jan Schuurhuis5Department of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, Cancer Center VU University Medical Center, 1081 HV Amsterdam, The NetherlandsMeasurable residual disease (MRD) in AML, assessed by multicolor flow cytometry, is an important prognostic factor. Progenitors are key populations in defining MRD, and cases of MRD involving these progenitors are calculated as percentage of WBC and referred to as white blood cell MRD (WBC-MRD). Two main compartments of WBC-MRD can be defined: (1) the AML part of the total primitive/progenitor (CD34+, CD117+, CD133+) compartment (referred to as primitive marker MRD; PM-MRD) and (2) the total progenitor compartment (% of WBC, referred to as PM%), which is the main quantitative determinant of WBC-MRD. Both are related as follows: WBC-MRD = PM-MRD × PM%. We explored the relative contribution of each parameter to the prognostic impact. In the HOVON/SAKK study H102 (300 patients), based on two objectively assessed cut-off points (2.34% and 10%), PM-MRD was found to offer an independent prognostic parameter that was able to identify three patient groups with different prognoses with larger discriminative power than WBC-MRD. In line with this, the PM% parameter itself showed no prognostic impact, implying that the prognostic impact of WBC-MRD results from the PM-MRD parameter it contains. Moreover, the presence of the PM% parameter in WBC-MRD may cause WBC-MRD false positivity and WBC-MRD false negativity. For the latter, at present, it is clinically relevant that PM-MRD ≥ 10% identifies a patient sub-group with a poor prognosis that is currently classified as good prognosis MRD<sup>negative</sup> using the European LeukemiaNet 0.1% consensus MRD cut-off value. These observations suggest that residual disease analysis using PM-MRD should be conducted.https://www.mdpi.com/2072-6694/13/11/2597acute myeloid leukemiaminimal/measurable residual diseasemultiparameter flow cytometryprimitive compartmentprognostic valueMRD false negativity |
| spellingShingle | Diana Hanekamp Jesse M. Tettero Gert J. Ossenkoppele Angèle Kelder Jacqueline Cloos Gerrit Jan Schuurhuis AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML Cancers acute myeloid leukemia minimal/measurable residual disease multiparameter flow cytometry primitive compartment prognostic value MRD false negativity |
| title | AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML |
| title_full | AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML |
| title_fullStr | AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML |
| title_full_unstemmed | AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML |
| title_short | AML/Normal Progenitor Balance Instead of Total Tumor Load (MRD) Accounts for Prognostic Impact of Flowcytometric Residual Disease in AML |
| title_sort | aml normal progenitor balance instead of total tumor load mrd accounts for prognostic impact of flowcytometric residual disease in aml |
| topic | acute myeloid leukemia minimal/measurable residual disease multiparameter flow cytometry primitive compartment prognostic value MRD false negativity |
| url | https://www.mdpi.com/2072-6694/13/11/2597 |
| work_keys_str_mv | AT dianahanekamp amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml AT jessemtettero amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml AT gertjossenkoppele amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml AT angelekelder amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml AT jacquelinecloos amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml AT gerritjanschuurhuis amlnormalprogenitorbalanceinsteadoftotaltumorloadmrdaccountsforprognosticimpactofflowcytometricresidualdiseaseinaml |