Features of techniques currently employed for MRD detection in ALL
| . | General statements . | Pros . | Cons . |
|---|---|---|---|
| Flow cytometry | Aberrant antigene expression | Applicable for almost all ALL patients | Immunophenotypic shifts of leukemic cells |
| Sensitivity depends on technology (number of colors) and on cell input | Availability of methodology in many laboratories | Expanded and altered precursor-B-cell compartment during regeneration | |
| Rapid | Low cellularity during/after induction | ||
| Quantitative | Relatively high costs (depends on cell input, number of markers/colors and ulterior cytometer use) | ||
| Additional information on benign cells | Limited sensitivity/applicability using 3- to 4-color flow cytometry | ||
| Additional information on malignant cells | ≥ 6-color flow cytometry: extensive knowledge and experience for sensitive and standardized analysis needed | ||
| Identification and monitoring of treatment targets possible | No sample asservation and retrospective analysis possible (on-site availability of expert operators necessary) | ||
| Growing standardization (mainly throughout Europe) | |||
| DNA-based RQ-PCR | Targets mainly Ig and TCR gene rearrangements but also MLL gene rearrangements or SIL-TAL-deletions | Applicable for almost all ALL patients | Time-consuming marker characterization |
| High sensitivity | Potential instability of targets (clonal evolution phenomena, therefore need for preferably 2 targets/patient) | ||
| High degree of standardization | Extensive knowledge and experience needed | ||
| Accepted and uniformly used definition of quantitative range and sensitivity | Relatively expensive | ||
| Well-established stratification tool in various clinical protocols | |||
| Most published data for evidence-based treatment decisions | |||
| Stability of DNA (multicenter setting, shipment time) | |||
| Possibility of sample storage and retrospective/batch analysis | |||
| Quantitative RT-PCR of fusion transcripts | Targets mainly BCR-ABL transcripts (∼ 35% of adult B-cell precursor ALL) | High sensitivity | Useful only in a minority of patients |
| Unequivocal link with leukemic/preleukemic clone | Instability of RNA | ||
| Stability of target during course of treatment | Uncertain quantitation because of unknown number of RNA transcripts/cell (potential differences during course of treatment) | ||
| Fast | False positivity resulting from cross-contamination | ||
| Relatively cheap | Standardization necessary |
| . | General statements . | Pros . | Cons . |
|---|---|---|---|
| Flow cytometry | Aberrant antigene expression | Applicable for almost all ALL patients | Immunophenotypic shifts of leukemic cells |
| Sensitivity depends on technology (number of colors) and on cell input | Availability of methodology in many laboratories | Expanded and altered precursor-B-cell compartment during regeneration | |
| Rapid | Low cellularity during/after induction | ||
| Quantitative | Relatively high costs (depends on cell input, number of markers/colors and ulterior cytometer use) | ||
| Additional information on benign cells | Limited sensitivity/applicability using 3- to 4-color flow cytometry | ||
| Additional information on malignant cells | ≥ 6-color flow cytometry: extensive knowledge and experience for sensitive and standardized analysis needed | ||
| Identification and monitoring of treatment targets possible | No sample asservation and retrospective analysis possible (on-site availability of expert operators necessary) | ||
| Growing standardization (mainly throughout Europe) | |||
| DNA-based RQ-PCR | Targets mainly Ig and TCR gene rearrangements but also MLL gene rearrangements or SIL-TAL-deletions | Applicable for almost all ALL patients | Time-consuming marker characterization |
| High sensitivity | Potential instability of targets (clonal evolution phenomena, therefore need for preferably 2 targets/patient) | ||
| High degree of standardization | Extensive knowledge and experience needed | ||
| Accepted and uniformly used definition of quantitative range and sensitivity | Relatively expensive | ||
| Well-established stratification tool in various clinical protocols | |||
| Most published data for evidence-based treatment decisions | |||
| Stability of DNA (multicenter setting, shipment time) | |||
| Possibility of sample storage and retrospective/batch analysis | |||
| Quantitative RT-PCR of fusion transcripts | Targets mainly BCR-ABL transcripts (∼ 35% of adult B-cell precursor ALL) | High sensitivity | Useful only in a minority of patients |
| Unequivocal link with leukemic/preleukemic clone | Instability of RNA | ||
| Stability of target during course of treatment | Uncertain quantitation because of unknown number of RNA transcripts/cell (potential differences during course of treatment) | ||
| Fast | False positivity resulting from cross-contamination | ||
| Relatively cheap | Standardization necessary |