Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that involves the uncontrolled clonal proliferation of blasts in the bone marrow and peripheral blood. It is characterized by clonal evolution and genetic heterogeneity [1-3]. Since cytogenetic profiles have become important indicators of prognosis in AML, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have incorporated certain cytogenetic and molecular abnormalities in AML classifications and risk stratifications. Internal tandem duplication in FMS-like tyrosine kinase 3 (
All AML patients with
Demographic characteristics, laboratory findings, treatments, toxicities, and outcome data were collected by reviewing medical records. AML classification was determined according to the French-American-British (FAB) criteria. Cytogenetic and genetic analyses were conducted using the trypsin-Giemsa banding technique and fluorescent in situ hybridization (FISH) on bone marrow cells at diagnosis. All patients had their
Prior to 2014, the induction chemotherapy protocol for pediatric AML patients in our institution was BH-AC-based (N4-Behenoy1-1-b-D-arabinofuranosy1cytosine) and consisted of enocitabine (300 mg/m2/day) for 7–10 days, idarubicin (IDA, 12 mg/m2/day) for 3 days, and intrathecal (IT) cytarabine . Starting in 2014, our center began to utilize a cytarabine-based induction regimen consisting of 2 courses, the first of which involved a continuous intravenous (IV) cytarabine infusion (200 mg/m2/day) for 7 days, IDA (12 mg/m2/day) for 3 days, and IT cytarabine. The second course consisted of 8 doses of IV cytarabine (1,500 mg/m2), mitoxantrone (12 mg/m2) for 2 days, and IT cytarabine. Patients with primary refractory disease received various salvage chemotherapies, as further elucidated in the results section. After chemotherapy, patients with
OS was defined as the duration from diagnosis to death or last follow-up, and EFS was defined as the duration from diagnosis to the first event (consisting of death or relapse). Primary refractory disease was not considered an event. Relapse free survival (RFS) was defined as the duration in months from the end of the primary treatment (HSCT) to relapse. The occurrence of death without relapse was not included as an event for RFS. Data on living patients and those who had died from any cause without relapse were recorded until the date of death or last follow-up, using a cut-off date of June 1, 2020. CR was defined as morphological remission (<5% blasts) in the bone marrow, and primary CR (CR1) was defined as morphological remission after the first course of induction chemotherapy. Primary refractory cancer to BH-AC-based induction was defined as morphological persistence (>5% blasts) in the bone marrow after induction chemotherapy. For cytarabine-based therapy, primary refractory disease was defined as >20% blasts in the bone marrow after the first course of induction chemotherapy and/or >5% blasts in the marrow after both courses of induction chemotherapy. The neutrophil engraftment date was defined as 3 consecutive days with an absolute neutrophil count (ANC) greater than 0.5×109/L after infusion.
Clinical and laboratory data were analyzed using standard statistical methods. The OS, EFS, and RFS were analyzed using the Kaplan-Meier method and the difference in survival rates was determined using the log-rank test, with results expressed as percentages±standard error. Statistical significance was defined as a
A total of 18 patients were newly diagnosed with non-M3 AML with
Fig. 1 and Table 2 outline the patients’ treatments and outcomes. All 18 patients received induction chemotherapy with either a BH-AC-based or cytarabine-based regimen. Fourteen patients received BH-AC-based induction chemotherapy and the other 4 patients received cytarabine-based induction. Thirteen patients achieved primary CR (72.2%), of which 11 were in the BH-AC group (11/14, 79%) and 2 were in the cytarabine group (2/4, 50%). The CR1 rates between the 2 induction chemotherapy regimens were not significantly different (
Apart from the 1 patient who was refractory to treatment, the other 17 patients in CR underwent HSCT. Nine patients received grafts from matched unrelated donors (MUDs), 5 from matched related donors (MRDs), and 3 from haploidentical donors. Of the 9 MUD grafts, 6 were 10/10 HLA-compatible and 3 were 9/10 HLA-compatible. The median neutrophil engraftment dates for MRDs, MUDs, and haploidentical donors were 11 (10–12 days), 14 (11–19 days), and 18 (16–20 days), respectively. All 17 patients showed evidence of engraftment in the bone marrow 1 month after HSCT and there were no engraftment failures. GVHD was seen in 7 patients, of which 6 received MUD grafts and 1 received MRD grafts. The 2 patients with acute GVHD of the skin both received MUD grafts and were treated with short-term steroids. There were 4 cases of pulmonary chronic GVHD. These patients were treated with steroids with or without imatinib. One patient with pulmonary GVHD died during treatment related to this complication (patient 2). There were 5 patients with veno-occlusive disease (VOD), 1 of which eventually died during treatment related to this complication (patient 11) (Table 2).
One patient who received a MUD graft and 3 who received MRD grafts relapsed after HSCT. Although the relapse rate was highest among MRD recipients, RFS was not statistically different between the donor groups (haploidentical 100%, MUD 88.9%, MRD 25.0%,
This retrospective study outlined the clinical course and evaluated the outcomes of pediatric AML patients with
In 2004, our institution reported a study that analyzed newly diagnosed AML patients from 1996 to 2003 and found 4 patients with
In this study, we detected the presence of
FLT3 inhibitors were not part of the treatment regimen in this study; however, these novel agents have been readily used and studied in the adult population and show promising results . In vitro studies have reported that FLT3 inhibitors work synergistically with chemotherapy to induce cytotoxicity [22, 23]. Selective next generation FLT3 therapies (gliteritinib, crenolanib, quizartinib) have greater specificity for FLT3 and higher potency than multitargeted TKIs (midostaurin and sorafenib), and clinical trials have shown an improvement in OS even in relapsed/refractory patients [2, 19]. This is promising because relapse is common in these patients, and relapsed patients usually present with higher
In summary, our study demonstrated a relapse rate of 22% after HSCT and OS and EFS rates of 53.8±12.1% and 53.6±12.1% in pediatric AML patients with
*This study was supported by a grant from the SNUH Research Fund (No. 0320200110).
No potential conflicts of interest relevant to this article were reported.