Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate

Abrahamsson, Jonas; Forestier, Erik; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Òlafur G.; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik

doi:10.1200/jco.2010.30.6829

Cited by 165 publications

(172 citation statements)

References 22 publications

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“…Both are independent prognostic factors and are usually essential elements of the risk group classification. [59][60][61] Most study groups evaluate treatment response morphologically in the bone marrow after the first (eg, on day 15 or day 28) and second induction courses. This may be challenging in hypoplastic bone marrows.…”

Section: Response and Prognosismentioning

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

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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 ...

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Section: Response and Prognosismentioning

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

481

526

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“…Protocol details including drug doses have been published previously. 20 Children below one year of age or with body weight below 10 kg received doses calculated according to body weight instead of body surface with 1 m 2 = 30 kg. No dose adjustment was recommended in overweight patients.…”

Section: Effect Of Age and Body Weight On Toxicity And Survival In Pementioning

confidence: 99%

Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004

Løhmann

Abrahamsson²,

et al. 2016

Haematologica

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T reatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first induction course of NOPHO-AML 2004 (n=318). Toxicity following induction and consolidation courses (n=6) was analyzed. The probabilities of toxicity and death were determined using time-to-event analyses with Cox multivariate proportional hazard regression for comparative analyses. Age 10-17 years was associated with sepsis with hypotension [hazard ratio 2.3 (95% confidence interval 1.1-4.6)]. Being overweight (>1 standard deviation) was associated with requiring supplemental oxygen [1.9 (1.0-3.5)]. The 5-year event-free and overall survival were 47% and 71%. Children aged 10-17 years showed a trend for inferior 5-year overall survival compared to children aged 2-9 (64% vs. 76%; P=0.07). Infants showed a trend for superior 5-year event-free survival (66% vs. 43%; P=0.06). Overweight children aged 10-17 years showed a trend for superior survival [5-year event-free survival 59% vs. 40% (P=0.09) and 5-year overall survival 78% vs. 56% (P=0.06)] compared to healthy weight children aged 10-17 years. In conclusion, children aged 10-17 years and overweight children had a higher risk of grade 3-4 toxicity. Children aged 10-17 years showed inferior survival, but, unexpectedly, in this age group overweight children tended to have increased survival. This suggests different pharmacokinetics of chemotherapeutic drugs in adolescents and warrants further studies.

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“…Unfortunately, one-third of the patients eventually relapse [1][2][3][4][5][6][7][8]. Over the past years, new therapies have been designed to improve the prognosis in AML including the development of antigen-targeted therapies.…”

Section: Introductionmentioning

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

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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

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Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate

Abstract: The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.

Cited by 165 publications

References 22 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

Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004

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

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