Pediatric protocol confers favorable outcomes for adolescents, young adults with ALL
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Use of a modified pediatric protocol produced favorable outcomes for adolescents and young adults with acute lymphoblastic leukemia, according to retrospective study results presented at Society of Hematologic Oncology Annual Meeting.
Investigators characterized OS and EFS rates as promising; however, venous thromboembolism and symptomatic avascular necrosis each occurred among more than 10% of patients.
“More work is certainly needed to further improve outcomes and decrease toxicities,” researcher Saleem Eldadah, MD, of Princess Noorah Oncology Center in Saudi Arabia, said during a presentation.
Prior studies have shown adolescent and young adult (AYA) patients with Philadelphia chromosome-negative ALL whose treatment follows pediatric or pediatric-inspired ALL protocols achieved better outcomes than those historically reported with adult protocols. Benefits included lower all-cause mortality at 3 years, as well as lower rates of relapse and nonrelapse mortality.
Princess Noorah Oncology Center has used a modified pediatric ALL protocol for AYA patients with Ph-ALL since 2003 in hopes of improving outcomes for this population.
Eldadah and colleagues evaluated outcomes for 95 consecutive AYA patients (age range, 14-39 years; 54.7% aged 14 to 18 years) treated at the center from January 2003 to December 2019.
Most patients were male (62.1%), had pre-B ALL phenotype (75.8%), had white blood cell count less than 50 x 109/L (74.7%) and had central nervous system-negative status (90.5%). Those with CNS-positive status received 24 Gy of cranial radiotherapy, but prophylactic CNS irradiation was not used.
About one-quarter (24.2%) had normal cytogenetics, and the majority (93.7%) underwent treatment in 2007 or later.
All patients underwent a 4-week induction, consolidation for 8 weeks, 8 weeks of interim maintenance with high-dose methotrexate (administered in four doses, each 14 days apart), delayed intensification for 8 weeks, a second 8-week period of interim maintenance with Capizzi methotrexate, and a final 30-month maintenance period.
Researchers used dexamethasone as the steroid during induction and delayed intensification, and they used prednisolone during maintenance. Patients with pre-B ALL received 10 infusions of rituximab (Rituxan; Genentech, Biogen), patients who were minimal residual disease-positive after consolidation received blinatumomab (Blincyto, Amgen), and those who developed neutropenia received antimicrobial prophylaxis and granulocyte colony-stimulating factor.
Researchers reported a 94.7% complete remission rate, with five (5.3%) induction failures and three (3.2%) induction deaths.
Eldadah and colleagues assessed minimal residual disease by multicolor flow cytometry, and they defined positivity as 0.01% or higher. An end-of-induction evaluation showed 72% of the 86 evaluable patients achieved minimal residual disease negativity.
Median follow-up was 4.9 years.
Researchers reported a 5-year OS rate of 80% and a 5-year EFS rate of 65%. OS and EFS did not differ by age or phenotype.
The cumulative incidence of relapse was 22.1% (n = 21), with 13 patients developing isolated bone marrow relapses, seven developing isolated CNS relapses and one developing combined relapse.
Fourteen of 21 (66.6%) patients who relapsed achieved a second complete remission with salvage therapy, and six (28.6%) remained alive at last follow-up.
Sixteen patients underwent allogeneic stem cell transplant. At last follow-up, four remained in first complete remission and 12 remained in second complete remission.
Six patients (6.3%) died in remission. These included three who developed complications after allogeneic stem cell transplant, two who died of sepsis and one who died in a traffic accident.
Treatment-related toxicities included VTE (16.8%), symptomatic avascular necrosis (13.7%), grade 3 or grade 4 peripheral neuropathy (14.7%), hyperglycemia requiring insulin during induction (17.8%) and symptomatic pancreatitis (4.2%).
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Eldadah S, et al. Abstract ALL-312. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting); Sept. 9-12, 2020.
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