Response criteria for ALL
| Category . | Definition . |
|---|---|
| Hematologic response criteria | |
| CR∗ | BM blasts <5% |
| Absence of extramedullary disease | |
| Absolute neutrophil count >1 × 109/L | |
| Platelet count >100 × 109/L (independence of red cell transfusions) | |
| If available: MRD <1%66 | |
| CRi† | All CR criteria except for residual thrombocytopenia |
| <100 × 109/L or neutropenia <1 × 109/L | |
| If available: MRD <1%66 | |
| Morphologic leukemia-free state‡ | BM blasts <5% |
| Absence of extramedullary disease | |
| If available: MRD <1%66 | |
| PR§ | Relevant in the setting of phase 1 and 2 clinical trials only; all hematologic criteria of CR; decrease of BM-blast percentage from 5% to 25%; and decrease of pretreatment BM-blast percentage by at least 50% |
| If available: CR if MRD <1%66 | |
| Failure | None of the above If available: MRD ≥1%66 |
| MRD response criteria (variant 1)|| | |
| Complete MRD response | No detectable MRD¶ |
| MRD failure | MRD above 0.01% (ie, 10–4) |
| MRD other | |
| Negative | MRD negative with insufficient sensitivity |
| Positive/intermediate | MRD positive below 0.01%, quantifiable |
| MRD positive below 0.01%, nonquantifiable | |
| MRD positive, nonquantifiable | |
| MRD response criteria (variant 2)|| | |
| MRD complete response | No detectable MRD¶ |
| MRD persistence | Any quantifiable MRD |
| Criteria for extramedullary response assessment | Published criteria for NHL65 PET in case of CRu/PR according to published criteria for NHL69 |
| Category . | Definition . |
|---|---|
| Hematologic response criteria | |
| CR∗ | BM blasts <5% |
| Absence of extramedullary disease | |
| Absolute neutrophil count >1 × 109/L | |
| Platelet count >100 × 109/L (independence of red cell transfusions) | |
| If available: MRD <1%66 | |
| CRi† | All CR criteria except for residual thrombocytopenia |
| <100 × 109/L or neutropenia <1 × 109/L | |
| If available: MRD <1%66 | |
| Morphologic leukemia-free state‡ | BM blasts <5% |
| Absence of extramedullary disease | |
| If available: MRD <1%66 | |
| PR§ | Relevant in the setting of phase 1 and 2 clinical trials only; all hematologic criteria of CR; decrease of BM-blast percentage from 5% to 25%; and decrease of pretreatment BM-blast percentage by at least 50% |
| If available: CR if MRD <1%66 | |
| Failure | None of the above If available: MRD ≥1%66 |
| MRD response criteria (variant 1)|| | |
| Complete MRD response | No detectable MRD¶ |
| MRD failure | MRD above 0.01% (ie, 10–4) |
| MRD other | |
| Negative | MRD negative with insufficient sensitivity |
| Positive/intermediate | MRD positive below 0.01%, quantifiable |
| MRD positive below 0.01%, nonquantifiable | |
| MRD positive, nonquantifiable | |
| MRD response criteria (variant 2)|| | |
| MRD complete response | No detectable MRD¶ |
| MRD persistence | Any quantifiable MRD |
| Criteria for extramedullary response assessment | Published criteria for NHL65 PET in case of CRu/PR according to published criteria for NHL69 |
This table is modified from Döhner et al.71
All criteria need to be fulfilled; marrow evaluation should be based on a count of 200 nucleated cells in an aspirate with spicules; if ambiguous, consider repeat exam after 5 to 7 days; a marrow biopsy should be performed in cases of dry tap, or if no spicules are obtained; no minimum duration of response required.
CRi is of value in protocols using intensified induction or double induction strategies, in which hematologic recovery is not awaited, but intensive therapy will be continued. In such protocols, CR may even not be achieved during the entire treatment plan. In these instances, the overall remission rate should include CR and CRi patients.
This category may be useful in the clinical development of novel agents within phase 1 clinical trials, in which a transient morphologic leukemia-free state may be achieved at the time of early response assessment.
Marrow should not merely be aplastic; at least 200 cells should be enumerated, or cellularity should be at least 10%.71 Any PR should be confirmed or falsified by parallel MRD assessment.
Confirmation of any MRD response requires the application of standardized methods with minimum technical requirements29 in reference laboratories.
Confirmation of negative MRD requires that technical requirements for establishment of sensitivity (usual: 0.01%) of each individual TP are fulfilled.