Table 6.

Response criteria in AML

 CR without minimal residual disease (CRMRD−)If studied pretreatment, CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFCSensitivities vary by marker tested, and by method used; therefore, test used and sensitivity of the assay should be reported; analyses should be done in experienced laboratories (centralized diagnostics)
 Complete remission (CR)Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 109/L (1000/µL); platelet count ≥100 × 109/L (100 000/µL)MRD+ or unknown
 CR with incomplete hematologic recovery (CRi)All CR criteria except for residual neutropenia (<1.0 × 109/L [1000/µL]) or thrombocytopenia (<100 × 109/L [100 000/µL])
 Morphologic leukemia-free state (MLFS)Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery requiredMarrow should not merely be “aplastic”; at least 200 cells should be enumerated or cellularity should be at least 10%
 Partial remission (PR)All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%Especially important in the context of phase 1-2 clinical trials
Treatment failure
 Primary refractory diseaseNo CR or CRi after 2 courses of intensive induction treatment; excluding patients with death in aplasia or death due to indeterminate causeRegimens containing higher doses of cytarabine (see Table 8) are generally considered as the best option for patients not responding to a first cycle of 7+3; the likelihood of responding to such regimens is lower after failure of a first
 Death in aplasiaDeaths occurring ≥7 d following completion of initial treatment while cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 d of death, without evidence of persistent leukemia
 Death from indeterminate causeDeaths occurring before completion of therapy, or <7 d following its completion; or deaths occurring ≥7 d following completion of initial therapy with no blasts in the blood, but no bone marrow examination available
Response criteria for clinical trials only
 Stable diseaseAbsence of CRMRD−, CR, CRi, PR, MLFS; and criteria for PD not metPeriod of stable disease should last at least 3 mo
 Progressive disease (PD)*,Evidence for an increase in bone marrow blast percentage and/or increase of absolute blast counts in the blood:Category mainly applies for older patient given low-intensity or single-agent “targeted therapies” in clinical trials
• >50% increase in marrow blasts over baseline (a minimum 15% point increase is required in cases with <30% blasts at baseline; or persistent marrow blast percentage of >70% over at least 3 mo; without at least a 100% improvement in ANC to an absolute level (>0.5 × 109/L [500/µL], and/or platelet count to >50 × 109/L [50 000/µL] nontransfused); orIn general, at least 2 cycles of a novel agent should be administered
• >50% increase in peripheral blasts (WBC × % blasts) to >25 × 109/L (>25 000/μL) (in the absence of differentiation syndrome); orSome protocols may require blast increase in 2 consecutive marrow assessments at least 4 wk apart; the date of progression should then be defined as of the first observation date
• New extramedullary diseaseSome protocols may allow transient addition of hydroxyurea to lower blast counts
“Progressive disease” is usually accompanied by a decline in ANC and platelets and increased transfusion requirement and decline in performance status or increase in symptoms
 Hematologic relapse (after CRMRD−, CR, CRi)Bone marrow blasts ≥5%; or reappearance of blasts in the blood; or development of extramedullary disease
 Molecular relapse (after CRMRD−)If studied pretreatment, reoccurrence of MRD as assessed by RT-qPCR or by MFCTest applied, sensitivity of the assay, and cutoff values used must be reported; analyses should be done in experienced laboratories (centralized diagnostics)
  • ANC, absolute neutrophil count; IDH, isocitrate dehydrogenase; MLFS, morphologic leukemia-free state; WBC, white blood cell.

  • * The authors acknowledge that this new provisional category is arbitrarily defined; the category aims at harmonizing the various definitions used in different clinical trials.

  • Certain targeted therapies, for example, those inhibiting mutant IDH proteins, may cause a differentiation syndrome, that is, a transient increase in the percentage of bone marrow blasts and an absolute increase in blood blasts; in the setting of therapy with such compounds, an increase in blasts may not necessarily indicate PD.