Response criteria in AML
| Category . | Definition . |
|---|---|
| Complete remission (CR)* | Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 × 109/L (1000/μL); platelet count > 80 × 109/L (80 000/μL); independence of red cell transfusions |
| CR with incomplete recovery (CRi)† | All CR criteria except for residual neutropenia (< 1.0 × 109/L [1000/μL]) or thrombocytopenia (< 80 × 109/L [80 000/μL]) |
| Treatment failure | |
| Resistant disease (RD) | Failure to achieve CR or CRi (general practice; phase 2/3 trials), or failure to achieve CR, CRi, or PR (phase 1 trials); only includes patients surviving ≥ 7 days after completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination (this should be stated by bone marrow examination < day 42 and at the end of intensification courses) |
| Early death | |
| Death in aplasia | Death occurring ≥ 7 days after completion of initial treatment while cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 days of death, without evidence of persistent leukemia (< day 42) |
| Death from indeterminate cause | |
| Early bleeding/leukostasis | Deaths occurring before completion of therapy, or < 7 days after its completion; or deaths occurring ≥ 7 days after completion of initial therapy with no blasts in the blood, but no bone marrow examination available (< day 42) |
| Relapse‡ | Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease |
| Category . | Definition . |
|---|---|
| Complete remission (CR)* | Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 × 109/L (1000/μL); platelet count > 80 × 109/L (80 000/μL); independence of red cell transfusions |
| CR with incomplete recovery (CRi)† | All CR criteria except for residual neutropenia (< 1.0 × 109/L [1000/μL]) or thrombocytopenia (< 80 × 109/L [80 000/μL]) |
| Treatment failure | |
| Resistant disease (RD) | Failure to achieve CR or CRi (general practice; phase 2/3 trials), or failure to achieve CR, CRi, or PR (phase 1 trials); only includes patients surviving ≥ 7 days after completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination (this should be stated by bone marrow examination < day 42 and at the end of intensification courses) |
| Early death | |
| Death in aplasia | Death occurring ≥ 7 days after completion of initial treatment while cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 days of death, without evidence of persistent leukemia (< day 42) |
| Death from indeterminate cause | |
| Early bleeding/leukostasis | Deaths occurring before completion of therapy, or < 7 days after its completion; or deaths occurring ≥ 7 days after completion of initial therapy with no blasts in the blood, but no bone marrow examination available (< day 42) |
| Relapse‡ | Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease |
Definitions of response criteria are based primarily on those given by Cheson et al2 and amended by Creutzig and Kaspers.225 Table 5 is analogous to the table of Döhner et al.4
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 repeating examination after 5-7 days; flow cytometric evaluation may help to distinguish between persistent leukemia and regenerating normal marrow; a marrow biopsy should be performed in cases of dry tap, or if no spicules are obtained; no minimum duration of response required. The categories morphologic leukemia-free state, partial remission (PR), cytogenetic CR (CRc), and molecular CR (CRm) may be useful in the clinical development of novel agents in phase 1 or 2 clinical trials. For definitions, see Döhner et al.4
The criterion of CRi is of value in protocols that use 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 in the course of the entire treatment plan. In these instances, the overall remission rate should include CR and CRi patients. Some patients may not achieve complete hematologic recovery, even with longer observation times. As treatment courses should be very condensed (with minimal delay) in pediatric patients, treatment is continued, even without complete platelet recovery. Therefore, the recommended cut-off value for platelets indicating CR is 80 × 109/L.
In patients with low blast percentages (5%-10%), a repeat marrow should be performed to confirm relapse. Appearance of new dysplastic changes should be closely monitored for emerging relapse. In a patient who has been recently treated, dysplasia or a transient increase in blasts may reflect a chemotherapy effect and recovery of hematopoiesis. Cytogenetics should be tested to distinguish true relapse from therapy-related MDS/AML.