AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia

Cooper, Todd M.; Franklin, Janet; Gerbing, Robert B.; Alonzo, Todd A.; Hurwitz, Craig A.; Raimondi, Susana C.; Hirsch, Betsy A.; Smith, Franklin O.; Mathew, Prasad; Arceci, Robert J.; Feusner, James; Iannone, Robert; Lavey, Robert S.; Meshinchi, Soheil; Gamis, Alan S.

doi:10.1002/cncr.26190

Cited by 178 publications

(192 citation statements)

References 46 publications

Supporting

Mentioning

178

Contrasting

Unclassified

Order By: Relevance

“…180,[183][184][185] Recent data from a prospective nonrandomized COG trial showed that GO did not cause increased toxicity, but data on efficacy are pending. 186 However, as the approved indications for GO have been revised in the United States by the FDA request, it may not be easily available for use in pediatric AML outside of clinical trials. …”

Section: Antibody-targeted Drugsmentioning

confidence: 99%

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Creutzig

Heuvel‐Eibrink

Gibson

et al. 2012

Blood

Self Cite

489

526

View full text Add to dashboard Cite

IntroductionChildhood acute myeloid leukemia (AML) is a rare and heterogeneous disease, with an incidence of 7 cases per million children younger than 15 years. In high-income countries, intensive therapy in conjunction with effective supportive care has increased survival rates to ϳ 70%. In 1990 and 2003, expert working groups made recommendations for diagnosis, outcomes, standardization of response criteria, and reporting standards for AML. 1,2 Recent improvements in identifying the molecular genetics and pathogenesis of AML have been implemented in the new World Health Organization (WHO) classification of AML. 3 These changes, and the definition of new diagnostic and prognostic markers and their associated targeted therapies, have prompted the update of earlier recommendations by an international group, on behalf of the European LeukemiaNet for AML in adults in 2010. 4 Despite broad overlap in the diagnostic and treatment recommendations for AML for children and adults, there are important differences in both the diagnostic criteria and disease management, which merit age-specific recommendations. The absence of published recommendations specific for pediatric AML motivated an international group of pediatric hematologists and oncologists (panel and participating groups see "Appendix") to develop evidence-and expert opinionbased consensus recommendations for the diagnosis and management of AML in children, incorporating emerging information on the biology of the disease. The scope of the review is presented in the "Appendix." Recommendations for specific subgroups are also included. This article discusses diagnostic procedures and initial workup, prognostic factors, response criteria, and management, and in particular focuses on differences between adults and children with AML. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From WHO classification and pediatric AMLThe recent WHO 2008 classification is applicable to both adult and pediatric AML 3,5 and has been summarized by Döhner et al. 4 The classification contains most, but not all, cytogenetic subgroups specific to children. Differences in genetic background between children and adults are given in Table 1 and discussed further in "Cytogenetics."Compared with previous classifications (European Group of Immunologic Characterization of Leukemias [EGIL], WHO 2001), 6 the new WHO classification introduced a stringently defined subclass of acute leukemias of ambiguous lineage (mixed phenotype acute leukemias [MPALs]), mainly on the basis of detailed immunophenotypic criteria (Table 2) or presence of t(9;22)(q34; q11.2)/BCR-ABL1 or t(v;11q23)/MLL rearrangement. 3,5,6 The new classification aims to create uniform subgroups defined by unifying molecular targets, which allow selection of specific treatment. Diagnostic procedures and initial workupThe minimal diagnostic requirements in childhood AML are morphology with cytochemistry, immunophenotyping, karyotyping, FISH, and specific molecular genetics in the bone marrow, which is comparable ...

show abstract

Section: Antibody-targeted Drugsmentioning

confidence: 99%

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Creutzig

Heuvel‐Eibrink

Gibson

et al. 2012

Blood

Self Cite

489

526

View full text Add to dashboard Cite

show abstract

“…Details of these studies have been previously described. [23][24][25][26] AAML03P1 (N 5 350) and CCG-2941/2961 (N 5 1106) enrolled patients 0 to 21 years of age, whereas AAML0531 (N 5 1070) enrolled patients that were 0 to 30 years of age. S0106 (N 5 595) enrolled patients 18 to 60 years of age.…”

Section: Patient Samplesmentioning

confidence: 99%

NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report

Ostronoff

Othus

Gerbing

et al. 2014

Blood

Self Cite

109

107

View full text Add to dashboard Cite

Key Points• Coexpression of NUP98/ NSD1 and FLT3/ITD in AML is associated with very low complete remission rates and poor survival.• It is the interaction between NUP98/NSD1 and FLT3/ITD that determines poor outcome in NUP98/NSD1-associated AML.NUP98/NSD1 has recently been reported in association with poor outcome in acute myeloid leukemia (AML). Previous studies also observed a high overlap between NUP98/ NSD1 and FLT3/ITD, raising the question as to whether the reported poor outcome is due to NUP98/NSD1 or caused by the co-occurrence of these 2 genetic lesions. We aimed to determine the prognostic significance of NUP98/NSD1 in the context of FLT3/ITD AML. A total of 1421 patients enrolled in 5 consecutive Children's Oncology Group/Children's Cancer Group and SWOG trials were evaluated. NUP98/NSD1 was found in 15% of FLT3/ ITD and 7% of cytogenetically normal (CN)-AML. Those with dual FLT3/ITD and NUP98/ NSD1 (82% of NUP98/NSD1 patients) had a complete remission rate of 27% vs 69% in FLT3/ ITD without NUP98/NSD1 (P < .001). The corresponding 3-year overall survival was 31% vs 48% (P 5 .011), respectively. In CN-AML, patients with concomitant NUP98/NSD1 and FLT3/ITD had a worse outcome than those harboring NUP98/NSD1 only. In multivariate analysis, the dual NUP98/NSD1 and FLT3/ITD remained an independent predictor of poor outcome, and NUP98/NSD1 without FLT3/ITD lost its prognostic significance. Our study demonstrates that it is the interaction between NUP98/NSD1 and FLT3/ITD that determines the poor outcome of patients with NUP98/NSD1 disease. (Blood. 2014;124(15):2400-2407

show abstract

“…Twenty-seven articles were included based on their abstracts. After reading full-text articles, 14 studies were included in this study [4,[21][22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Search Strategymentioning

confidence: 99%

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

Parigger

Zwaan

Reinhardt

et al. 2016

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Gemtuzumab ozogamicin, an anti-tumour antibiotic linked to an anti-CD33 antibody (Mylotarg®), has been well studied in AML in adults but to a lesser extent in children. No review has yet been published on the dose-related toxicity and efficacy of gemtuzumab ozogamicin in pediatric AML patients. Here we looked at 14 studies then scatterplots and linear regressions were used to estimate the relationship between the dose of gemtuzumab and its toxicity and efficacy. A nonsignificant increase in bilirubin level and in incidence of veno-occlusive disease was seen with higher doses of gemtuzumab ozogamicin when used as single-agent. In terms of efficacy, even a low dose of 3 mg/m 2 of gemtuzumab ozogamicin can have antileukemic effect, but available data do not allow conclusions on its dose-dependency. Data indicate that higher doses of gemtuzumab ozogamicin account for more adverse events. The data do not show that a high dose is required for anti-leukemic efficacy of gemtuzumab ozogamicin. This study also indicates that there seems to be a role for gemtuzumab ozogamicin in the treatment of pediatric AML and further studies are required to assess its optimal dose, schedule and balance between efficacy and side-effects. ARTICLE HISTORY

show abstract

AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia

Cited by 178 publications

References 46 publications

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

Contact Info

Product

Resources

About