Overall survival (OS) according to response status after course 1. (A) All patients. (B) Patients at good and standard risk (patients known to be at poor risk excluded). (C) Patients at standard risk. (D) OS for patients at standard risk censored at allogeneic stem-cell transplantation. CR, complete remission; CRi, complete remission with absolute neutrophil count
Fig 2.
Forest plots for overall survival…
Fig 2.
Forest plots for overall survival by multiparametric flow cytometry-MRD status for patients in…
Fig 2. Forest plots for overall survival by multiparametric flow cytometry-MRD status for patients in complete remission. (A) After course 1. (B) After course 2, stratified by cytogenetic risk group and NCRI AML17 risk score group. CBF, core binding factor; HR, hazard ratio; MRD, measurable residual disease; NS, not significant; O-E, observed minus expected; Var, variance.
Fig 3.
Forest plots for (A) overall…
Fig 3.
Forest plots for (A) overall survival and (B) relapse by combined response data…
Fig 3. Forest plots for (A) overall survival and (B) relapse by combined response data after courses 1 and 2. Effect of multiparametric flow cytometry-MRD status in CR after course 2 stratified by post-C1 response status. C1, course 1; CR, complete remission; HR, hazard ratio; MRD, measurable residual disease; NS, not significant; O-E, observed minus expected; PR, partial remission; RD, resistant disease; Var, variance.
Fig 4.
Standard-risk NPM1- wild type. (A)…
Fig 4.
Standard-risk NPM1- wild type. (A) Cumulative incidence of relapse by MRD level. (MRD−…
Fig 4. Standard-risk NPM1-wild type. (A) Cumulative incidence of relapse by MRD level. (MRD− v MRD+ < 0.1% v MRD+ ≥ 0.1%) after courses 1 and 2. (B) Overall survival (OS) according to MRD status after course 2 (MRD− v MRD+). (Not shown: MRD+ ≥ 0.1%, OS of 24%; MRD+ < 0.1%, OS of 39%). (C) Mantel-Byar analysis for survival according to first CR stem-cell transplant by MRD after course 2. CR, complete remission; CRi, complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL; HR, hazard ratio; MRD, measurable residual disease; NS, not significant; O-E, observed minus expected; Var, variance.
Fig A1.
Flowchart of treatments given to…
Fig A1.
Flowchart of treatments given to patients in the NCRI AML17 trial. (A) Pre-October…
Fig A1. Flowchart of treatments given to patients in the NCRI AML17 trial. (A) Pre-October 2011 (induction gemtuzumab ozogamicin randomization). (B) Post-October 2011 (daunorubicin dose randomization in induction). Note: patients who did not satisfy the hepatic entry criteria (liver function 2 with course 2 if they did not receive it by gemtuzumab ozogamicin randomization with course 1. From June, 2012 patients with informative real-time quantitative polymerase chain reaction (RT-qPCR) MRD markers could enter the ‘Monitor vs no Monitor’ randomization that investigates the impact of serial RT-qPCR monitoring post completion of treatment on outcome, quality of life and health economics. ADE, cytarabine, daunorubicin, and etoposide; APL, acute promyelocytic leukemia; CBF, core binding factor; CEP-701, lestaurtinib; DA, daunorubicin and cytarabine; GO, gemtuzumab ozogamicin (3 or 6 mg/m2); FLAG-Ida, fludarabine, cytarabine, GCSF, and idarubicin; FLT3, FMS-like tyrosine kinase-3; mTOR, everolimus; R, randomization.
Fig A2.
CONSORT diagram. Outline of patient…
Fig A2.
CONSORT diagram. Outline of patient sample flow for MRD study. (*) Includes patients…
Fig A2. CONSORT diagram. Outline of patient sample flow for MRD study. (*) Includes patients for whom remission status could not be classified as exact timing of any remission was unavailable. CR, complete remission; C1, course 1, C2, course 2. LAIP, leukemia-associated–immunophenotype; MRD, measurable residual disease.
Fig A3.
OS according to response status…
Fig A3.
OS according to response status after course 1. (A) All patients. OS censored…
Fig A3. OS according to response status after course 1. (A) All patients. OS censored at allogeneic SCT. (B) NPM1–wild-type patients at standard risk. (C) NPM1–wild-type patients at standard risk, censored at allogeneic SCT. CR, complete remission; MRD, measurable residual disease; OS, overall survival; PR, partial remission; RD, resistant disease; SCT, stem-cell transplantation.
Fig A4.
Forest plots for relapse by…
Fig A4.
Forest plots for relapse by multiparametric flow cytometry-MRD status for patients in CR…
Fig A4. Forest plots for relapse by multiparametric flow cytometry-MRD status for patients in CR (A) after course 1 and (B) after course 2 stratified by cytogenetic risk group and NCRI AML 17 risk score group. CR, complete remission; MRD, measurable residual disease.
Fig A5.
Cumulative incidence of relapse by…
Fig A5.
Cumulative incidence of relapse by multiparametric flow cytometry -MRD level. (MRD− v MRD+…
Fig A5. Cumulative incidence of relapse by multiparametric flow cytometry -MRD level. (MRD− v MRD+ < 0.1% v MRD+ ≥ 0.1%) after course 1. (A) CBF AML. (B) Standard-risk NPM1 mutant. AML, acute myeloid leukemia; CBF, core binding factor; MRD, measurable residual disease; MRD < 0.1%, MRD+ < 0.1%; MRD 0.1%+, MRD+ ≥ 0.1%.
Fig A6.
Standard-risk NPM1 -wild type. Overall…
Fig A6.
Standard-risk NPM1 -wild type. Overall survival (OS) according to multiparametric flow cytometry-MRD status…
Fig A6. Standard-risk NPM1-wild type. Overall survival (OS) according to multiparametric flow cytometry-MRD status after course 2, censored at any allogeneic stem-cell transplantation. CR, complete remission; MRD, measurable residual disease.
Fig A7.
OS according to response status…
Fig A7.
OS according to response status after course 1, applying European LeukemiaNet (ELN)/Cheson criteria…
Fig A7. OS according to response status after course 1, applying European LeukemiaNet (ELN)/Cheson criteria for PR and RD instead of MRC criteria (ELN criteria for PR: all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25% with decrease of pretreatment bone marrow blast percentage by ≥ 50%). (A) All patients. (B) Patients at good and standard risk (patients known to be at poor risk excluded). (C) Patients at standard risk. (D) Patients at standard risk, OS censored at allogeneic SCT. CR, complete remission; MRD, measurable residual disease; OS, overall survival; PR, partial remission; RD, resistant disease; SCT, stem-cell transplantation.