Pediatric Acute Myeloid Leukemia—Past, Present, and Future

Reinhardt, Dirk; Antoniou, Evangelia; Waack, Katharina

doi:10.3390/jcm11030504

Cited by 44 publications

(40 citation statements)

References 111 publications

(121 reference statements)

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“…Over the last few decades, there has been a significant improvement in survival in pediatric AML in highincome countries (HICs) [2]. This improvement has been achieved through better risk stratification, improved supportive care, and allogeneic hematopoietic stem cell transplantation (HSCT) [3,4]. The outcomes of pediatric AML in low-income countries (LICs) and low and middle-income countries (LMICs) have been poor compared to HICs due to limited resources, high cost of treatment, infections, lack of access to allogeneic HSCT, delayed and moribund presentation, and treatment abandonment [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial

et al. 2022

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The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a randomized controlled trial to ascertain the benefit of a three-drug induction regimen. Patients aged 1–18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study’s primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives included comparing the composite complete remission (cCR) rates, overall survival (OS), and toxicities. The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The cCR rate in the DA and ADE arm were 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%, respectively (p = 0.74). There were no significant differences in toxicities between the regimens. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202).

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Section: Introductionmentioning

confidence: 99%

Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial

et al. 2022

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“…Treatment decisions are based on risk stratification and further guided by the initial response to treatment [ 5 , 6 , 23 ]. Most international pediatric study groups (AIEOP/BFM/FRANCE/UK/COG/Japan) define risk classification according to genetic/molecular abnormalities and response to treatment by the measurement of residual disease by flow and morphology [ 24 ]. In particular, favorable prognostic factors include t(8;21)(q22;q22)/RUNX1-RUNX1T1, t(15;17)(q22;q21)/PML-RARA, NPM1-mutated AML, and CEBPA double mutation [ 6 ].AML with MLL translocations has variable outcomes, depending on the associated translocation and occurs more frequently in children compared to in adults [ 25 ].…”

Section: Therapeutic Considerations: Past and Futurementioning

confidence: 99%

“…However, a large meta-analysis of 10 trials including 1661 patients with pediatric AML showed a shorter OS for FLT3-ITD mutated AML [ 31 ]. AIEOP-BFM AML 2020 proposed risk stratification in three groups (standard, intermediate, and high-risk AML); AML is high risk when minimal residual disease (MRD) is ≥1% after induction course 1 or ≥0.1% at induction 2 or blast count is ≥5% at induction 1 (only if flow results are not informative) with one of genetic/molecular aberration at diagnosis, as described in Table 1 [ 24 ].…”

Section: Therapeutic Considerations: Past and Futurementioning

confidence: 99%

High-Risk Acute Myeloid Leukemia: A Pediatric Prospective

et al. 2022

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Pediatric acute myeloid leukemia is a clonal disorder characterized by malignant transformation of the hematopoietic stem cell. The incidence and the outcome remain inferior when compared to pediatric ALL, although prognosis has improved in the last decades, with 80% overall survival rate reported in some studies. The standard therapeutic approach is a combined cytarabine and anthracycline-based regimen followed by consolidation with allogeneic stem cell transplantation (allo-SCT) for high-risk AML and allo-SCT for non-high-risk patients only in second complete remission after relapse. In the last decade, several drugs have been used in clinical trials to improve outcomes in pediatric AML treatment.

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“…Although the current, highly intensive, chemotherapeutic regimens used in pediatric acute myeloid leukemia (AML) have contributed to immense improvement in overall survival rates [1][2][3], the associated serious treatment-related toxicities remain an important concern [4,5]. In particular, the chemotherapy-induced severe and prolonged neutropenia predisposes patients to bacterial and fungal infections, which may cause life-threatening complications throughout treatment and significant treatment delay [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study

Weelderen

Klein

Goemans

et al. 2022

Cancers

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Bloodstream infections (BSIs), especially those caused by Gram-negative rods (GNR) and viridans group streptococci (VGS), are common and potentially life-threatening complications of pediatric acute myeloid leukemia (AML) treatment. Limited literature is available on prophylactic regimens. We retrospectively evaluated the effect of different antibacterial prophylaxis regimens on the incidence of febrile neutropenic (FN) episodes and bacterial BSIs. Medical records of children (0–18 years) diagnosed with de novo AML and treated at two Dutch centers from May 1998 to March 2021 were studied. Data were analyzed per chemotherapy course and consecutive neutropenic period. A total of 82 patients had 316 evaluable courses: 92 were given with single-agent ciprofloxacin, 138 with penicillin plus ciprofloxacin, and 51 with teicoplanin plus ciprofloxacin. The remaining 35 courses with various other prophylaxis regimens were not statistically compared. During courses with teicoplanin plus ciprofloxacin, significantly fewer FN episodes (43% vs. 90% and 75%; p < 0.0001) and bacterial BSIs (4% vs. 63% and 33%; p < 0.0001) occurred than with single-agent ciprofloxacin and penicillin plus ciprofloxacin, respectively. GNR and VGS BSIs did not occur with teicoplanin plus ciprofloxacin and no bacterial BSI-related pediatric intensive care unit (PICU) admissions were required, whereas, with single-agent ciprofloxacin and penicillin plus ciprofloxacin, GNR BSIs occurred in 8% and 1% (p = 0.004), VGS BSIs in 24% and 14% (p = 0.0005), and BSI-related PICU admissions were required in 8% and 2% of the courses (p = 0.029), respectively. Teicoplanin plus ciprofloxacin as antibacterial prophylaxis is associated with a lower incidence of FN episodes and bacterial BSIs. This may be a good prophylactic regimen for pediatric AML patients during treatment.

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Pediatric Acute Myeloid Leukemia—Past, Present, and Future

Abstract: This review reports about the main steps of development in pediatric acute myeloid leukemia (AML) concerning diagnostics, treatment, risk groups, and outcomes. Finally, a short overview of present and future approaches is given.

Cited by 44 publications

References 111 publications

Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial

Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial

High-Risk Acute Myeloid Leukemia: A Pediatric Prospective

Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study

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