Prognostic (risk) groups under clinical evaluation

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Age and presenting leukocyte count (using NCI risk-group criteria).[3]

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Age and presenting leukocyte count (using NCI risk-group criteria).[3]

NCI standard (low) risk: Includes children aged 1 year to <10 years with WBC <50,000/µL at the time of diagnosis.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Age and presenting leukocyte count (using NCI risk-group criteria).[3]

NCI high risk: Includes children aged ≥10 years and/or children who have WBC ≥50,000/µL at the time of diagnosis.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Extramedullary disease (presence or absence of CNS and/or testicular leukemia).

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia).

CNS1: Absence of blasts on CSF cytospin preparation, regardless of the number of WBCs.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia).

CNS2: Presence of <5 WBC/μL in CSF and cytospin positive for blasts; or traumatic LP, ≥5 WBC/μL, cytospin positive for blasts but negative by Steinherz/Bleyer algorithm.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia).

CNS3 is divided and defined as follows:

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia). › CNS3 is divided and defined as follows:

CNS3a: <10 RBC/μL; ≥5 WBC/μL and cytospin positive for blasts.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia). › CNS3 is divided and defined as follows:

CNS3b: ≥10 RBC/μL; ≥5 WBC/μL and positive by Steinherz/Bleyer algorithm.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Extramedullary disease (presence or absence of CNS and/or testicular leukemia). › CNS3 is divided and defined as follows:

CNS3c: Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome).

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Genomic alterations in leukemia cells.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Day 8 peripheral blood MRD.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Day 29 bone marrow morphological response and MRD.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

EOC MRD.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Steroid pretreatment.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Favorable cytogenetic features include the following:

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Favorable cytogenetic features include the following:

Hyperdiploidy with double trisomies of chromosomes 4 and 10 (double trisomy); or

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Favorable cytogenetic features include the following:

ETV6::RUNX1 fusion.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Unfavorable cytogenetic features include the following:

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Unfavorable cytogenetic features include the following:

Hypodiploidy (<44 chromosomes or DNA index <0.81).

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Unfavorable cytogenetic features include the following:

KMT2A rearrangements.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Unfavorable cytogenetic features include the following:

t(17;19)(q21-q22;p13.3) or resultant TCF3::HLF fusion transcript.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Unfavorable cytogenetic features include the following:

Intrachromosomal amplification of chromosome 21 (iAMP21); and

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity. › Unfavorable cytogenetic features include the following:

BCR::ABL1 (Ph+ or t(9;22)(q34;q11)). Patients with BCR::ABL1 ALL are treated on a separate clinical trial.

COG AALL1731 (NCT03914625) standard-risk and AALL1732 (NCT03959085) high-risk clinical trials: The COG classifies patients into six risk groups for patients with B-ALL (standard-risk favorable, standard-risk average, standard-risk high, high-risk favorable, high risk, and very high risk) on the basis of the following:Morphological assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on separate trials and are not risk classified in this way.For patients with B-ALL, the definitions of favorable, unfavorable, and neutral cytogenetics are as follows:NCI standard-risk patients are divided into a highly favorable group (standard-risk favorable; 5-year DFS rate, >95%), a group with favorable outcome (standard-risk average; 5-year DFS rate, 90%–95%), and a group with a 5-year DFS rate below 90% (standard-risk high). Patients classified as standard-risk high receive postinduction backbone chemotherapy as per high-risk B-ALL regimens with intensified consolidation, interim maintenance, and reinduction therapy. Criteria for these three groups are provided in Table 6, Table 7, and Table 8 below.High-risk favorable B-ALL is defined by the characteristics in Table 9. These patients have an EFS rate higher than 90% on past COG clinical trials for high-risk patients. High-risk B-ALL is defined by the characteristics in Table 10. NCI standard-risk patients are elevated to high-risk status based on steroid pretreatment and CNS and/or testicular involvement.NCI high-risk patients with EOC marrow MRD ≥0.01% are classified as very high risk and are eligible for a chimeric antigen receptor (CAR) T-cell clinical trial in first remission (NCT03792633).Patients with B-ALL and Down syndrome are classified into risk groups similar to other children, but Down syndrome patients classified as high risk receive a treatment regimen that is modified to reduce toxicity.

Neutral cytogenetics: Lacking favorable and unfavorable cytogenetic features.