Treatment of children with Down syndrome

A large retrospective study that included 653 patients with Down syndrome and ALL who were treated between 1995 to 2004 reported the following results:[74]

A large retrospective study that included 653 patients with Down syndrome and ALL who were treated between 1995 to 2004 reported the following results:[74]

Patients with Down syndrome had lower CR rates (97% vs. 99%, P < .001), higher cumulative incidence of relapse rates (26% vs. 15%, P < .001), and higher treatment-related mortality rates (7.7% vs. 2.3%, P < .001), compared with patients without Down syndrome.

A large retrospective study that included 653 patients with Down syndrome and ALL who were treated between 1995 to 2004 reported the following results:[74]

For patients with Down syndrome and ALL, treatment-related mortality occurred at a higher rate during all phases of therapy, including maintenance. The rates of treatment-related mortality during induction were 2.8% and 4.9% during the remaining treatment phases after CR had been achieved. The most common cause of treatment-related mortality was infection.

A large retrospective study that included 653 patients with Down syndrome and ALL who were treated between 1995 to 2004 reported the following results:[74]

Among the patients with Down syndrome, age younger than 6 years, WBC count of less than 10,000/μL, and the presence of the ETV6::RUNX1 fusion (observed in 8% of patients) were independent predictors of favorable EFS.

In a report of 2,811 children with ALL enrolled on the COG P9900 classification study, 80 patients (3%) had Down syndrome. Age, sex, WBC count, and risk group were similar between patients with and without Down syndrome, but a lower percentage of patients with Down syndrome had ETV6::RUNX1 (2.5% vs. 24%, P < .001) or trisomies 4 and 10 (7.7% vs. 24%, P < .001).[71]

In a report of 2,811 children with ALL enrolled on the COG P9900 classification study, 80 patients (3%) had Down syndrome. Age, sex, WBC count, and risk group were similar between patients with and without Down syndrome, but a lower percentage of patients with Down syndrome had ETV6::RUNX1 (2.5% vs. 24%, P < .001) or trisomies 4 and 10 (7.7% vs. 24%, P < .001).[71]

The 5-year EFS and OS rates were inferior in children with Down syndrome: 69.9% versus 78.1% (P = .078), and 85.8% versus 90.0% (P = .033), respectively.

In a report of 2,811 children with ALL enrolled on the COG P9900 classification study, 80 patients (3%) had Down syndrome. Age, sex, WBC count, and risk group were similar between patients with and without Down syndrome, but a lower percentage of patients with Down syndrome had ETV6::RUNX1 (2.5% vs. 24%, P < .001) or trisomies 4 and 10 (7.7% vs. 24%, P < .001).[71]

However, when children with KMT2A rearrangements, BCR::ABL1, ETV6::RUNX1, and trisomies 4 and 10 were excluded from the analysis, the EFS and OS rates were similar for children with and without Down syndrome (EFS rates, 68.0% [± 9.3%] vs. 70.5% [± 1.9%], P = .817; OS rates, 86.7% [± 6.7%] vs. 85.4% [± 1.5%]; P = .852).

In the CCG-1991 (NCT00005945) study for children with standard-risk B-ALL (2000–2005), patients (including those with Down syndrome) were randomly assigned to receive an interim maintenance phase consisting of either escalating doses of intravenous methotrexate without leucovorin rescue or standard low-dose oral methotrexate given with vincristine, dexamethasone, and mercaptopurine.[85]

In the CCG-1991 (NCT00005945) study for children with standard-risk B-ALL (2000–2005), patients (including those with Down syndrome) were randomly assigned to receive an interim maintenance phase consisting of either escalating doses of intravenous methotrexate without leucovorin rescue or standard low-dose oral methotrexate given with vincristine, dexamethasone, and mercaptopurine.[85]

The 10-year EFS rates were 94.4% (± 5.4%) for patients with Down syndrome randomly assigned to receive escalating-dose IV methotrexate (N = 31), versus 81.5% (± 6.6%) for patients who received oral low-dose methotrexate (N = 44).

In the CCG-1991 (NCT00005945) study for children with standard-risk B-ALL (2000–2005), patients (including those with Down syndrome) were randomly assigned to receive an interim maintenance phase consisting of either escalating doses of intravenous methotrexate without leucovorin rescue or standard low-dose oral methotrexate given with vincristine, dexamethasone, and mercaptopurine.[85]

The mean total tolerated dose of methotrexate on the escalating IV arm was lower in patients with Down syndrome than patients without Down syndrome.

In the CCG-1991 (NCT00005945) study for children with standard-risk B-ALL (2000–2005), patients (including those with Down syndrome) were randomly assigned to receive an interim maintenance phase consisting of either escalating doses of intravenous methotrexate without leucovorin rescue or standard low-dose oral methotrexate given with vincristine, dexamethasone, and mercaptopurine.[85]

The incidence of mucositis was increased in patients with Down syndrome who received escalating-dose methotrexate, compared with patients without Down syndrome, but there was no increase in hepatic toxicity, infections, or treatment-related deaths.

On DFCI ALL Consortium protocols, children with Down syndrome receive the same risk-stratified therapy as other patients, without any dose reductions or modifications. An analysis of two consecutive trials conducted between 2000 to 2011 found the following:[84]

On DFCI ALL Consortium protocols, children with Down syndrome receive the same risk-stratified therapy as other patients, without any dose reductions or modifications. An analysis of two consecutive trials conducted between 2000 to 2011 found the following:[84]

The 5-year EFS and OS rates of patients with Down syndrome (N = 38) were similar to that of patients without Down syndrome (N = 1,248) (EFS rates, 91% vs. 84%; OS rates, 97% vs. 91%).

On DFCI ALL Consortium protocols, children with Down syndrome receive the same risk-stratified therapy as other patients, without any dose reductions or modifications. An analysis of two consecutive trials conducted between 2000 to 2011 found the following:[84]

All patients with Down syndrome achieved complete remission, and none of the patients experienced treatment-related mortality.

On DFCI ALL Consortium protocols, children with Down syndrome receive the same risk-stratified therapy as other patients, without any dose reductions or modifications. An analysis of two consecutive trials conducted between 2000 to 2011 found the following:[84]

Patients with Down syndrome had significantly higher rates of mucositis (52% vs. 12%, P < .001), non-CNS thrombosis (18% vs. 8%; P = .036), and seizure (16% vs. 5%, P = .010). Patients with Down syndrome also had a higher incidence of infections during all therapy phases.