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PITTSBURGH – In the current era, children with Down syndrome who have standard risk B-cell precursor acute lymphoblastic leukemia have event-free and overall survival rates nearly as good as those of other children with standard-risk B–ALL, results of a Children’s Oncology Group study show.
Among 5,311 children enrolled in the COG AALL0331 trial, a study of combination chemotherapy for young patients with newly diagnosed ALL, the 5-year event-free survival (EFS) rate for children with Down syndrome was 86%, compared with 89% for children without Down syndrome (P = .025).
Although the differences in EFS and OS were significant, ”overall in this study, Down syndrome ALL had an excellent outcome that was similar to those patients without Down syndrome,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The trial confirmed her group’s previous finding that there is a low rate of favorable cytogenetic features in patients with Down syndrome ALL; nonetheless, in the current study, 5-year continuous complete remission rates for standard-risk average, low, and high in patients with Down syndrome were similar to those for patients without Down syndrome, she said.
In the trial, patients were treated with a three-drug induction regimen, and following induction were assigned to standard-risk low, average, or high groups based on leukemia genetics and initial response to therapy.
Of the 5,311 children enrolled, 141 (2.7%) had Down syndrome, and these patients received risk-stratified therapy with additional supportive care guidelines, including leucovorin rescue after intrathecal methotrexate until maintenance. The care team strongly encouraged hospitalizations during high-risk blocks for this subgroup of patients until they experienced neutrophil recovery.
At the end of induction, patients who were judged to be standard-risk average were then randomized in a 2x2 design to either standard or intensified consolidation, and to standard interim maintenance with delayed intensification, or to intensified interim maintenance with delayed intensification.
The intensified interim maintenance with delayed intensification randomization was closed in 2008 because of superior results with escalating intravenous methotrexate during interim maintenance for standard-risk ALL patients treated in the CCG 1991 trial. Subsequently, all patients enrolled in AALL0331 received escalating intravenous methotrexate during interim maintenance.
Also in AALL0331, patients with Down syndrome who had standard-high ALL were given intensified consolidation and a single vs. double intensified interim maintenance with delayed intensification; patients without Down syndrome and standard risk high received the double intensified interim maintenance regimen.
Standard-risk low Down syndrome patients and non–Down syndrome patients participated in a randomization to additional pegaspargase doses during consolidation and interim maintenance.
There were no significant differences between patients with or without Down syndrome in the proportion of either rapid or slow early responses. Significantly fewer patients with Down syndrome had standard-risk low disease, and significantly more had average or high-risk disease.
Patients with Down syndrome initially had 11.5% excess risk for death during induction, but following additional treatment modifications, the excess risk decreased to 1.7%.
Among patients with Down syndrome, one died during intensive consolidation, and two died during delayed intensification. All three deaths were due to infections. No patients with Down syndrome died during maintenance.
Patients with Down syndrome also had a significantly increased risk for infection during induction (P less than .0001).
For patients with standard-risk low disease, 5-year EFS was 100% for those with Down syndrome, compared with 95.35% for patients without. Respective rates for standard risk average and high disease were 88.07% vs. 89.63%. and 82.35% vs. 86.18%.
Down syndrome was not an independent risk factor for survival in multivariate analyses accounting for risk group, Dr. Maloney said.
COG AALL0331 was supported by the National Cancer Institute. Dr. Maloney reported having no financial disclosures.
SOURCE: Maloney K et al. ASPHO 2018, Abstract PP 2001.
PITTSBURGH – In the current era, children with Down syndrome who have standard risk B-cell precursor acute lymphoblastic leukemia have event-free and overall survival rates nearly as good as those of other children with standard-risk B–ALL, results of a Children’s Oncology Group study show.
Among 5,311 children enrolled in the COG AALL0331 trial, a study of combination chemotherapy for young patients with newly diagnosed ALL, the 5-year event-free survival (EFS) rate for children with Down syndrome was 86%, compared with 89% for children without Down syndrome (P = .025).
Although the differences in EFS and OS were significant, ”overall in this study, Down syndrome ALL had an excellent outcome that was similar to those patients without Down syndrome,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The trial confirmed her group’s previous finding that there is a low rate of favorable cytogenetic features in patients with Down syndrome ALL; nonetheless, in the current study, 5-year continuous complete remission rates for standard-risk average, low, and high in patients with Down syndrome were similar to those for patients without Down syndrome, she said.
In the trial, patients were treated with a three-drug induction regimen, and following induction were assigned to standard-risk low, average, or high groups based on leukemia genetics and initial response to therapy.
Of the 5,311 children enrolled, 141 (2.7%) had Down syndrome, and these patients received risk-stratified therapy with additional supportive care guidelines, including leucovorin rescue after intrathecal methotrexate until maintenance. The care team strongly encouraged hospitalizations during high-risk blocks for this subgroup of patients until they experienced neutrophil recovery.
At the end of induction, patients who were judged to be standard-risk average were then randomized in a 2x2 design to either standard or intensified consolidation, and to standard interim maintenance with delayed intensification, or to intensified interim maintenance with delayed intensification.
The intensified interim maintenance with delayed intensification randomization was closed in 2008 because of superior results with escalating intravenous methotrexate during interim maintenance for standard-risk ALL patients treated in the CCG 1991 trial. Subsequently, all patients enrolled in AALL0331 received escalating intravenous methotrexate during interim maintenance.
Also in AALL0331, patients with Down syndrome who had standard-high ALL were given intensified consolidation and a single vs. double intensified interim maintenance with delayed intensification; patients without Down syndrome and standard risk high received the double intensified interim maintenance regimen.
Standard-risk low Down syndrome patients and non–Down syndrome patients participated in a randomization to additional pegaspargase doses during consolidation and interim maintenance.
There were no significant differences between patients with or without Down syndrome in the proportion of either rapid or slow early responses. Significantly fewer patients with Down syndrome had standard-risk low disease, and significantly more had average or high-risk disease.
Patients with Down syndrome initially had 11.5% excess risk for death during induction, but following additional treatment modifications, the excess risk decreased to 1.7%.
Among patients with Down syndrome, one died during intensive consolidation, and two died during delayed intensification. All three deaths were due to infections. No patients with Down syndrome died during maintenance.
Patients with Down syndrome also had a significantly increased risk for infection during induction (P less than .0001).
For patients with standard-risk low disease, 5-year EFS was 100% for those with Down syndrome, compared with 95.35% for patients without. Respective rates for standard risk average and high disease were 88.07% vs. 89.63%. and 82.35% vs. 86.18%.
Down syndrome was not an independent risk factor for survival in multivariate analyses accounting for risk group, Dr. Maloney said.
COG AALL0331 was supported by the National Cancer Institute. Dr. Maloney reported having no financial disclosures.
SOURCE: Maloney K et al. ASPHO 2018, Abstract PP 2001.
PITTSBURGH – In the current era, children with Down syndrome who have standard risk B-cell precursor acute lymphoblastic leukemia have event-free and overall survival rates nearly as good as those of other children with standard-risk B–ALL, results of a Children’s Oncology Group study show.
Among 5,311 children enrolled in the COG AALL0331 trial, a study of combination chemotherapy for young patients with newly diagnosed ALL, the 5-year event-free survival (EFS) rate for children with Down syndrome was 86%, compared with 89% for children without Down syndrome (P = .025).
Although the differences in EFS and OS were significant, ”overall in this study, Down syndrome ALL had an excellent outcome that was similar to those patients without Down syndrome,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
The trial confirmed her group’s previous finding that there is a low rate of favorable cytogenetic features in patients with Down syndrome ALL; nonetheless, in the current study, 5-year continuous complete remission rates for standard-risk average, low, and high in patients with Down syndrome were similar to those for patients without Down syndrome, she said.
In the trial, patients were treated with a three-drug induction regimen, and following induction were assigned to standard-risk low, average, or high groups based on leukemia genetics and initial response to therapy.
Of the 5,311 children enrolled, 141 (2.7%) had Down syndrome, and these patients received risk-stratified therapy with additional supportive care guidelines, including leucovorin rescue after intrathecal methotrexate until maintenance. The care team strongly encouraged hospitalizations during high-risk blocks for this subgroup of patients until they experienced neutrophil recovery.
At the end of induction, patients who were judged to be standard-risk average were then randomized in a 2x2 design to either standard or intensified consolidation, and to standard interim maintenance with delayed intensification, or to intensified interim maintenance with delayed intensification.
The intensified interim maintenance with delayed intensification randomization was closed in 2008 because of superior results with escalating intravenous methotrexate during interim maintenance for standard-risk ALL patients treated in the CCG 1991 trial. Subsequently, all patients enrolled in AALL0331 received escalating intravenous methotrexate during interim maintenance.
Also in AALL0331, patients with Down syndrome who had standard-high ALL were given intensified consolidation and a single vs. double intensified interim maintenance with delayed intensification; patients without Down syndrome and standard risk high received the double intensified interim maintenance regimen.
Standard-risk low Down syndrome patients and non–Down syndrome patients participated in a randomization to additional pegaspargase doses during consolidation and interim maintenance.
There were no significant differences between patients with or without Down syndrome in the proportion of either rapid or slow early responses. Significantly fewer patients with Down syndrome had standard-risk low disease, and significantly more had average or high-risk disease.
Patients with Down syndrome initially had 11.5% excess risk for death during induction, but following additional treatment modifications, the excess risk decreased to 1.7%.
Among patients with Down syndrome, one died during intensive consolidation, and two died during delayed intensification. All three deaths were due to infections. No patients with Down syndrome died during maintenance.
Patients with Down syndrome also had a significantly increased risk for infection during induction (P less than .0001).
For patients with standard-risk low disease, 5-year EFS was 100% for those with Down syndrome, compared with 95.35% for patients without. Respective rates for standard risk average and high disease were 88.07% vs. 89.63%. and 82.35% vs. 86.18%.
Down syndrome was not an independent risk factor for survival in multivariate analyses accounting for risk group, Dr. Maloney said.
COG AALL0331 was supported by the National Cancer Institute. Dr. Maloney reported having no financial disclosures.
SOURCE: Maloney K et al. ASPHO 2018, Abstract PP 2001.
REPORTING FROM ASPHO 2018
Key clinical point:
Major finding: The 5-year event-free survival rate for children with Down syndrome was 86% vs. 89% for children without Down syndrome (P = .025).
Study details: Follow-up of 5,311 children with newly diagnosed ALL in the COG AALL0331 trial.
Disclosures: COG AALL0331 was supported by the National Cancer Institute. Dr. Maloney reported having no financial disclosures.
Source: Maloney K et al. ASPHO 2018, Abstract PP 2001.