Infants with acute myeloid leukemia treated according to the Associazione Italiana di Ematologia e Oncologia Pediatrica 2002/01 protocol have an outcome comparable to that of older children

Masetti, Riccardo; Rondelli, Roberto; Mastronuzzi, Angela; Pierani, Paolo; Togni, Marco; Menna, Giuseppe; Pigazzi, Martina; Putti, Maria Caterina; Basso, Giuseppe; Pession, Andrea; Locatelli, Franco

doi:10.3324/haematol.2014.106526

Cited by 28 publications

(56 citation statements)

References 11 publications

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“…The outcome for infants treated according to NOPHO-AML 2004 was excellent (5-year EFS: 66%, 95%CI: 46%-79%, 5-year OS: 82%, 95%CI: 63%-91%) and confirm previous reports showing favorable outcome for infants. 19,34 High-dose cytarabine seems safe and effective in treating infants with AML, and our results do not support further dose reductions in infants as recommended by others. 14 Children aged 10-17 years were at higher risk of toxicity.…”

Section: A B C Dcontrasting

confidence: 52%

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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Section: A B C Dcontrasting

confidence: 52%

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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“…Infant acute myeloid leukaemia (AML), which accounts for approximately 10% of paediatric AML cases, has been conventionally defined as AML in patients aged <1 year. Infant AML is related to high frequencies of M4, M5 and M7 subtypes in the French‐American‐British (FAB) classification, high white blood cell (WBC) counts at diagnosis, and a high incidence of central nervous system involvement (Creutzig et al , ; Creutzig et al , ; Masetti et al , ). Molecular analysis of infant AML found 11q23/ KMT2A rearrangement ( KMT2A ‐R) to be the most frequent abnormality (Creutzig et al , ; Masetti et al , ), and t(7;12)(q36;p13)/ MNX1‐ETV6 and t(1;22)(p13;q13)/ RBM15‐MRTFA ( MKL1 ) have been repeatedly found (Ma et al , ; Mercher et al , ; von Bergh et al , ).…”

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confidence: 99%

“…Infant AML is related to high frequencies of M4, M5 and M7 subtypes in the French‐American‐British (FAB) classification, high white blood cell (WBC) counts at diagnosis, and a high incidence of central nervous system involvement (Creutzig et al , ; Creutzig et al , ; Masetti et al , ). Molecular analysis of infant AML found 11q23/ KMT2A rearrangement ( KMT2A ‐R) to be the most frequent abnormality (Creutzig et al , ; Masetti et al , ), and t(7;12)(q36;p13)/ MNX1‐ETV6 and t(1;22)(p13;q13)/ RBM15‐MRTFA ( MKL1 ) have been repeatedly found (Ma et al , ; Mercher et al , ; von Bergh et al , ). Moreover, recent studies have revealed the novel fusion genes, namely inv(16)(p13.3q24.3)/ CBFA2T3‐GLIS2 and t(11;12)(p15;p13)/ NUP98‐KDM5A in paediatric patients with FAB‐M7 AML (Gruber et al , ; Thiollier et al , ; de Rooij et al , ).…”

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confidence: 99%

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

et al. 2019

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Summary Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1–2 years with AML may have characteristics similar to that of infants. Thus, we analysed 723 paediatric AML patients treated on the Japanese AML99 and AML‐05 trials to identify characteristics of younger children. We identified patients aged <3 years (the younger group) as a distinct subgroup. KMT2A‐rearrangement (KMT2A‐R), CBFA2T3‐GLIS2, CBFB‐MYH11 and NUP98‐KDM5A were frequently found in the younger group. Prognostic analyses revealed poor 5‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) in patients with CBFA2T3‐GLIS2 (42%, 17% and 83%, respectively) and those with NUP98‐KDM5A (33%, 17% and 83%, respectively). Additionally, we identified KMT2A‐R and CBFB‐MYH11 as age‐specific prognostic markers. Regarding KMT2A‐R, the younger group had significantly better OS, EFS and CIR than the older group (aged 3 to <18 years) (P = 0·023, 0·011 and <0·001, respectively). Conversely, concerning CBFB‐MYH11, the younger group had significantly poor EFS and CIR than the older group (each P < 0·001), suggesting that certain molecular markers are linked to different prognoses according to age. Therefore, we characterized patients <3 years as a distinct subgroup of paediatric AML.

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“…[1][2][3][4] They are also at increased risk of pulmonary and infectious toxicities, early death (ED), and treatment-related mortality (TRM). 3,5,6 Despite these challenges, infants are typically treated with the same AML protocols used for older children and adolescents.…”

mentioning

confidence: 99%

“…3,5,6 Despite these challenges, infants are typically treated with the same AML protocols used for older children and adolescents. [2][3][4][6][7][8] Outcomes for infants with AML remain unsatisfactory, with overall survival (OS) and eventfree survival (EFS) rates of 56% to 76% and 44% to 72%, respectively.…”

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confidence: 99%

Gemtuzumab ozogamicin in infants with AML: results from the Children’s Oncology Group trials AAML03P1 and AAML0531

Guest

Aplenc

Sung

et al. 2017

Blood

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Infants with acute myeloid leukemia treated according to the Associazione Italiana di Ematologia e Oncologia Pediatrica 2002/01 protocol have an outcome comparable to that of older children

Cited by 28 publications

References 11 publications

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

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

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

Gemtuzumab ozogamicin in infants with AML: results from the Children’s Oncology Group trials AAML03P1 and AAML0531

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