Try a new search

Format these results:

Searched for:



Total Results:


Development of osteonecrosis and improved survival in B-ALL: results of Children's Oncology Group Trial AALL0232

Mattano, Leonard A; Devidas, Meenakshi; Loh, Mignon L; Raetz, Elizabeth A; Chen, Zhiguo; Winick, Naomi J; Hunger, Stephen P; Carroll, William L; Larsen, Eric C
Osteonecrosis is a significant toxicity of acute lymphoblastic leukemia (ALL) therapy. In retrospective analyses, superior event-free survival was noted among affected adolescents in an earlier trial. We prospectively assessed osteonecrosis incidence, characteristics, and risk factors in patients 1-30 years with newly diagnosed high-risk B-ALL on COG AALL0232. Patients were randomized to induction dexamethasone vs prednisone, and interim maintenance high-dose methotrexate vs escalating-dose Capizzi methotrexate/pegaspargase. Event-free and overall survival were compared between patients with/without imaging-confirmed osteonecrosis. Osteonecrosis developed in 322/2730 eligible, evaluable patients. The 5-year cumulative incidence was 12.2%. Risk was greater in patients ≥10 years (hazard ratio [HR], 7.23; P < 0.0001), particularly females (HR, 1.37; P = 0.0057), but lower in those with asparaginase allergy (HR, 0.60; P = 0.0077). Among rapid early responders ≥10 years, risk was greater with dexamethasone (HR, 1.84; P = 0.0003) and with prednisone/Capizzi (HR, 1.45; P = 0.044), even though neither therapy was independently associated with improved survival. Patients with osteonecrosis had higher 5-year event-free (HR, 0.51; P < 0.0001) and overall survival (HR, 0.42; P < 0.0001), and this was directly attributable to reduced relapse rates (HR, 0.57; P = 0.0014). Osteonecrosis in high-risk B-ALL patients is associated with improved survival, suggesting an important role for host factors in mediating both toxicity and enhanced efficacy of specific therapies.
PMID: 38062123
ISSN: 1476-5551
CID: 5591442

Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children's Oncology Group study

Wood, Brent L; Devidas, Meenakshi; Summers, Ryan J; Chen, Zhiguo; Asselin, Barbara; Rabin, Karen R; Zweidler-McKay, Patrick A; Winick, Naomi J; Borowitz, Michael J; Carroll, William L; Raetz, Elizabeth A; Loh, Mignon L; Hunger, Stephen P; Dunsmore, Kimberly P; Teachey, David T; Winter, Stuart S
The early thymic precursor (ETP) immunophenotype was previously reported to confer poor outcome in T-cell acute lymphoblastic leukemia (T-ALL). Between 2009 and 2014, 1256 newly diagnosed children and young adults enrolled in Children's Oncology Group (COG) AALL0434 were assessed for ETP status and minimal residual disease (MRD) using flow cytometry at a central reference laboratory. The subject phenotypes were categorized as ETP (n = 145; 11.5%), near-ETP (n = 209; 16.7%), or non-ETP (n = 902; 71.8%). Despite higher rates of induction failure for ETP (6.2%) and near-ETP (6.2%) than non-ETP (1.2%; P < .0001), all 3 groups showed excellent 5-year event-free survival (EFS) and overall survival (OS): ETP (80.4% ± 3.9% and 86.8 ± 3.4%, respectively), near-ETP (81.1% ± 3.3% and 89.6% ± 2.6%, respectively), and non-ETP (85.3% ± 1.4% and 90.0% ± 1.2%, respectively; P = .1679 and P = .3297, respectively). There was no difference in EFS or OS for subjects with a day-29 MRD <0.01% vs 0.01% to 0.1%. However, day-29 MRD ≥0.1% was associated with inferior EFS and OS for patients with near-ETP and non-ETP, but not for those with ETP. For subjects with day-29 MRD ≥1%, end-consolidation MRD ≥0.01% was a striking predictor of inferior EFS (80.9% ± 4.1% vs 52.4% ± 8.1%, respectively; P = .0001). When considered as a single variable, subjects with all 3 T-ALL phenotypes had similar outcomes and subjects with persistent postinduction disease had inferior outcomes, regardless of their ETP phenotype. This clinical trial was registered at AALL0434 as #NCT00408005.
PMID: 37556734
ISSN: 1528-0020
CID: 5613402

Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1)

Raetz, Elizabeth A; Teachey, David T; Minard, Charles; Liu, Xiaowei; Norris, Robin E; Denic, Kristina Z; Reid, Joel; Evensen, Nikki A; Gore, Lia; Fox, Elizabeth; Loh, Mignon L; Weigel, Brenda J; Carroll, William L
BACKGROUND:Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. PROCEDURE:/dose) was administered orally once daily for 21 consecutive days, first as a single agent (Days 1-3) and subsequently combined with re-induction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), followed by an expansion pharmacokinetic cohort. RESULTS:/dose orally for 21 days. No additional DLTs were observed in the dose determination or pharmacokinetic expansion cohorts, and overall rates of grade 3/4 nonhematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. CONCLUSIONS:/day for 21 days. Complete responses were observed among heavily pretreated patients.
PMID: 37553297
ISSN: 1545-5017
CID: 5619972

KMT2A partner genes in infant acute lymphoblastic leukemia have prognostic significance and correlate with age, white blood cell count, sex, and central nervous system involvement: a Children's Oncology Group P9407 trial study [Letter]

Robinson, Blaine W; Kairalla, John A; Devidas, Meenakshi; Carroll, Andrew J; Harvey, Richard C; Heerema, Nyla A; Willman, Cheryl L; Ball, Amanda R; Woods, Elliot C; Ballantyne, Nancy C; Urtishak, Karen A; Behm, Frederick G; Reaman, Gregory H; Hilden, Joanne M; Camitta, Bruce M; Winick, Naomi J; Pullen, Jeanette; Carroll, William L; Hunger, Stephen P; Dreyer, ZoAnn E; Felix, Carolyn A
PMID: 36861410
ISSN: 1592-8721
CID: 5631662

Flow cytometric assessment of leukemia-associated monocytes in childhood B-cell acute lymphoblastic leukemia outcome

Contreras Yametti, Gloria Paz; Evensen, Nikki A; Schloss, Jennifer; Aldebert, Clemence; Duan, Emily; Zhang, Yan; Hu, Jiyuan; Chambers, Tiffany M; Scheurer, Michael E; Teachey, David T; Rabin, Karen R; Raetz, Elizabeth A; Aifantis, Iannis; Carroll, William L; Witkowski, Matthew T
PMID: 37196626
ISSN: 2473-9537
CID: 5505192

Lupus anti-coagulant hypoprothrombinemia syndrome across different ages: a case report and review of the literature

Chumsky, Jessica; Kahn, Philip J; Carroll, William L; Pierce, Kristyn A; Hillier, Kirsty
Lupus anti-coagulant hypoprothrombinemia syndrome (LAHPS) is a rare condition that can be difficult to treat. It increases the risk of thrombosis and bleeding due to the presence of lupus anti-coagulant and factor II deficiency, respectively. There are a limited number of cases described in the literature. Herein we describe a case of LAHPS with bleeding symptoms as a first clinical manifestation of systemic lupus erythematosus (SLE) in an 8-year-old female. She has had multiple recurrences of her bleeding symptoms, requiring treatment with steroids, cyclophosphamide, mycophenolate mofetil, and rituximab. Her course was later complicated by development of arthritis and lupus nephritis. Her complicated course provides a new perspective on the clinical course and treatment of LAHPS. We also present a comprehensive literature review which demonstrates the difficulty in treating patients with LAHPS with underlying SLE and the variability of the clinical course and management of LAHPS depending on the age at presentation.
PMID: 37157007
ISSN: 1434-9949
CID: 5476922

Correction: Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932

Schore, Reuven J; Angiolillo, Anne L; Kairalla, John A; Devidas, Meenakshi; Rabin, Karen R; Zweidler-McKay, Patrick; Borowitz, Michael J; Wood, Brent; Carroll, Andrew J; Heerema, Nyla A; Relling, Mary V; Hitzler, Johann; Kadan-Lottick, Nina S; Maloney, Kelly; Wang, Cindy; Carroll, William L; Winick, Naomi J; Raetz, Elizabeth A; Loh, Mignon L; Hunger, Stephen P
PMID: 37157018
ISSN: 1476-5551
CID: 5509282

Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932 [Letter]

Schore, Reuven J; Angiolillo, Anne L; Kairalla, John A; Devidas, Meenakshi; Rabin, Karen R; Zweidler-McKay, Patrick; Borowitz, Michael J; Wood, Brent; Carroll, Andrew J; Heerema, Nyla A; Relling, Mary V; Hitzler, Johann; Kadan-Lottick, Nina S; Maloney, Kelly; Wang, Cindy; Carroll, William L; Winick, Naomi J; Raetz, Elizabeth A; Loh, Mignon L; Hunger, Stephen P
PMID: 36966262
ISSN: 1476-5551
CID: 5536392

Minimal residual disease predicts outcomes in KMT2A-rearranged but not KMT2A-germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631

Faulk, Kelly E; Kairalla, John A; Dreyer, ZoAnn E; Carroll, Andrew J; Heerema, Nyla A; Devidas, Meenakshi; Carroll, William L; Raetz, Elizabeth A; Loh, Mignon L; Hunger, Stephen P; Borowitz, Michael; Wang, Cindy; Guest, Erin; Brown, Patrick A
We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.01%) was: TP1: 25% (±6%) versus 49% (±7%; p = .0009); TP2: 21% (±8%) versus 47% (±7%; p < .0001); and TP3: 22% (±14%) versus 51% (±6%; p = .0178). For KMT2A-germline patients, 3-year EFS was: TP1: 88% (±12%) versus 87% (±5%; p = .73); TP2: 100% versus 88% (±5%; p = .24); and TP3: 100% versus 87% (±5%; p = .53). MRD was a strong independent outcome predictor in KMT2A-rearranged, but not KMT2A-germline infant ALL.
PMID: 37259259
ISSN: 1545-5017
CID: 5543352

Central Nervous System Status is Prognostic in T-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report

Gossai, Nathan; Devidas, Meenakshi; Chen, Zhiguo; Wood, Brent L; Zweidler-McKay, Patrick A; Rabin, Karen R; Loh, Mignon L; Raetz, Elizabeth A; Winick, Naomi J; Burke, Michael J; Carroll, Andrew J; Esiashvili, Natia; Heerema, Nyla A; Carroll, William L; Hunger, Stephen P; Dunsmore, Kimberly P; Winter, Stuart Sheldon; Teachey, David T
To determine the prognostic significance of central nervous system (CNS) leukemic involvement in newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL), outcomes on consecutive, phase 3 Children's Oncology Group (COG) clinical trials were examined. AALL0434 and AALL1231 tested efficacy of novel agents incorporated into augmented Berlin-Frankfurt-Münster (aBFM) therapy. In addition to testing study-specific chemotherapy through randomization, the AALL0434 regimen delivered cranial radiation (CRT) to the majority of subjects (90.8%), while AALL1231 intensified chemotherapy to eliminate CRT in 88.2% of subjects. In combined analysis of 2,164 T-ALL subjects (AALL0434: 1,550; AALL1231: 614), 1,564 were CNS-1 (72.3%), 441 CNS-2 (20.4%), and 159 CNS-3 (7.3%). The 4-year event-free survival (EFS) was similar for CNS-1 (85.1±1.0%) and CNS-2 (83.2±2.0%), but lower for CNS-3 (71.8±4.0%); p=0.0004. Subjects with CNS-1 and CNS-2 had similar 4-year overall-survival (OS) (90.1±0.8% and 90.5±1.5%), with OS for CNS-3 (82.7±3.4%); p=0.005. Despite therapeutic differences, outcomes for CNS-1 and CNS-2 were similar regardless of CRT, intensified corticosteroids or novel agents. Except for significantly superior outcomes with nelarabine on AALL0434 (4-year disease-free survival 93.1%±5.2%), EFS/OS was inferior with CNS-3 status, all of whom received CRT. Combined analyses of over 2,000 subjects with T-ALL, found that those with CNS-1 and CNS-2 status at diagnosis had similar outcomes. Unlike with B-ALL, CNS-2 status in T-ALL does not impact outcome in the context of aBFM therapy, without additional intrathecal therapy, with or without CRT. Although nelarabine improved outcomes for those with CNS-3 status, novel approaches are needed for further improvements.
PMID: 36603187
ISSN: 1528-0020
CID: 5433512