Citations 3
Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group
Rabin, Karen R. , Chen, Zhiguo , Ji, Lingyun , Kairalla, John A. , Hitzler, Johann , Carroll, Andrew J. , Heerema, Nyla A. , Borowitz, Michael J., Reshmi, Shalini C. , Bhojwani, Deepa , Maloney, Kelly W. , Mattano, Leonard A. , Larsen, Eric , Salzer, Wanda L. , Carroll, William L. , Raetz, Elizabeth A. , Loh, Mignon L. , Angiolillo, Anne , Ji, Lingyun , Hitzler, Johann K , Yang, Jun J.J. , Carroll, Andrew J , Wood, Brent L , Roberts, Kathryn G , Mullighan, Charles G , Harvey, Richard , Willman, Cheryl , Gastier‐Foster, Julie M. , Rheingold, Susan R , Maloney, Kelly W , Mattano, Leonard A , Schore, Reuven J , Burke, Michael J , Winick, Naomi Joan , Raetz, Elizabeth A , Loh, Mignon L , Hunger, Stephen P , Rabin, Karen R , Devidas, Meenakshi , Wood, Brent L. , Roberts, Kathryn G. , Mullighan, Charles G. , Harvey, Richard C. , Chen, I‐Ming , Willman, Cheryl L. , Hunger, Stephen P.
Journal of Clinical Oncology | October 27, 2023 | Volume: 42 | Issue: 2 | Pages: 218-227
PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% v 21.5%; P < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P < .0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 103/μL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P = .0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P < .0001), and induction death (3.4% v 0.8%; P < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P = .005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.
A Pilot Study of Azacitidine As Epigenetic Priming for Chemotherapy in Infants Less Than 1 Year of Age with KMT2A-Rearranged Acute Lymphoblastic Leukemia (ALL); Results from the Children's Oncology Group (COG) Trial AALL15P1
Kairalla, John A. , Hibbitts, Emily , Carroll, Andrew J. , Heerema, Nyla A. , Kubaney, Holly R. , August, Amanda, Wechsler, Daniel S. , Miles, Rodney R., Kihei, Cynthia D., Gore, Lia , Raetz, Elizabeth A. , Brown, Patrick A. , Guest, Erin M. , Devidas, Meenakshi , Pauly, Melinda , Reid, Joel M. , Hunger, Stephen P. , Loh, Mignon L.
Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 3256-3257
A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children’s Oncology Group Study AALL08P1
Rodriguez, Vilmarie , Kairalla, John A. , Salzer, Wanda L. , Raetz, Elizabeth A. , Loh, Mignon L. , Carroll, Andrew J. , Heerema, Nyla A. , Borowitz, Michael J., Asselin, Barbara L. , Carroll, William L. , Dreyer, ZoAnn E., Wood, Brent L. , Burke, Michael J , Devidas, Meenakshi , Winick, Naomi Joan , Hunger, Stephen P. , Dreyer, ZoAnn E. , Loh, Mignon L
Journal of Pediatric Hematology/Oncology | June 14, 2016 | Volume: 38 | Issue: 6 | Pages: 409-417
AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children’s Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events, and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥8 total doses of I-PEG and 50% (15/30) took ≤49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2 to 5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study.