Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

Larsen, Eric; Devidas, Meenakshi; Chen, Si; Salzer, Wanda L.; Raetz, Elizabeth A.; Loh, Mignon L.; Mattano, Leonard A.; Cole, Catherine; Eicher, Alisa L.; Haugan, Maureen; Sorenson, Mark; Heerema, Nyla A.; Carroll, Andrew A.; Gastier‐Foster, Julie M.; Borowitz, Michael J.; Wood, Brent L.; Willman, Cheryl L.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.

doi:10.1200/jco.2015.62.4544

Cited by 324 publications

(263 citation statements)

References 33 publications

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“…Despite these limitations, to date all reported cooperative trial groups used morphology-based definitions of induction failure. 4, 8, 9, 13, 24, 25 …”

Section: Discussionmentioning

confidence: 99%

“…Details of each clinical trial, including chemotherapy regimens and randomized treatment interventions are described elsewhere, and/or have been previously published (AALL03B1 – NCT00482352; AALL08B1 – NCT01142427; AALL0331 – NCT00103285; AALL0232 – NCT00075725; AALL0434 – NCT00408005). 3, 13, 14 Induction therapy with either three (AALL0331) or four drugs (AALL0232, AALL0434) was followed by post induction therapy, the intensity of which was determined by risk status, which included early response measures. 15 …”

Section: Methodsmentioning

confidence: 99%

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Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)

et al. 2018

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Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B- and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). While MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs. flow cytometry using patients age 1–30.99 years enrolled on Children’s Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N=9 350). Morphologic response was assessed locally as M1 (<5% lymphoblasts; remission), M2 (5–25%), or M3 (>25%). MRD was centrally measured by flow cytometry. 19.8% of patients with M2/M3 morphology had MRD<5%. M1 with MRD≥5% was less common in B-ALL (0.9%) than T-ALL (6.9%; p<0.0001). In B-ALL, M1/MRD≥5% was associated with superior 5-year event-free survival (EFS) than M2/MRD≥5% (59.1%±6.5% vs. 39.1%±7.9%; p=0.009), but was inferior to M1/MRD<5% (87.1%±0.4%; p<0.0001). MRD levels were higher in M2/MRD≥5% than M1/MRD≥5% patients. In T-ALL, EFS was not significantly different between M1/MRD≥5% and M2/MRD ≥5%. Patients with morphologic remission but MRD ≥5% have outcomes similar to those who fail to achieve morphological remission, and significantly inferior to those with M1 marrows and concordant MRD, suggesting that flow cytometry should augment the definition of remission in ALL.

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“…Despite these limitations, to date all reported cooperative trial groups used morphology-based definitions of induction failure. 4, 8, 9, 13, 24, 25 …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)

et al. 2018

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“…Trials AALL0331 [11] and AALL0932 enrolled 5164 and 5195 patients with SR B-ALL respectively, in which for the purpose of this analysis, we included only those patients that received a total of two doses of pegaspargase ( n = 1380) for a more homogeneous comparison, excluding patients on AALL0331 randomized to augmented Interim Maintenance and Delayed Intensification (DI) where two extra doses of pegaspargase were given. Patients enrolled on AALL0232 [12] (HR B-ALL) or AALL0434 [13] (T-ALL or T-lymphoblastic lymphoma (LL)) randomized to escalating methotrexate with pegaspargase for Interim Maintenance I were excluded from the analysis when comparing total rates of grade ≥3 HSR. However, these patients were included for comparisons for pegaspargase grade ≥3 HSR occurring after dose #2 or #3 (during Consolidation) to provide a more uniform group of HR B-ALL and T-ALL/LL patients receiving similar therapy.…”

Section: Methodsmentioning

confidence: 99%

Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials

Burke

Devidas

Maloney

et al. 2017

Leukemia & Lymphoma

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PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3–41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children’s Oncology Group (COG) leukemia trials (2003–2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003–2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection.

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“…Therefore, the strengths of these non-concentrated solutions are suitable to treat rheumatic and endocrine disorders as well as chemotherapy induced nausea and vomiting [12]. However, they require large-volume doses and are thereby inappropriate to treat diseases requiring high dosage regimen of dexamethasone such as haematological malignancies [13].…”

Section: Discussionmentioning

confidence: 99%

Preparation and Physico-Chemical Stability of Dexamethasone Oral Suspension

Binson

Venisse

Bacle³

et al. 2017

Pharmaceutical Technology in Hospital Pharmacy

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AbstractBackgroundDexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5 mg/mL dexamethasone oral suspension.MethodsA stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-SweetResultsThe mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17 mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period.ConclusionDexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2 °C or at 21±3 °C).

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Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

Cited by 324 publications

References 33 publications

Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)

Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)

Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials

Preparation and Physico-Chemical Stability of Dexamethasone Oral Suspension

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