The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (
In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including
According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as
Among the AML patients, intermediate-risk
Acute myeloid leukemia (AML) is characterized by the clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure [1, 2]. Previous studies have already shown the clinical and biological heterogeneity of AML [3, 4, 5, 6], and the advent of genome sequencing has revealed AML to be a highly complex and dynamic disease [7, 8, 9, 10]. Molecular and cytogenetic abnormalities are both powerful prognostic factors for AML and are included in the recent prognostic scoring system [11, 12, 13, 14, 15].
Allogeneic hematopoietic cell transplantation (allo-HCT) is considered the standard treatment for most patients with AML [16, 17]. After completing induction chemotherapy, the decision to proceed with allo-HCT or pursue a non-transplant approach for consolidation is mainly based on risk stratification. While allo-HCT does offer the highest cure rates based on a potent graft-versus-leukemia effect, it is also associated with a considerable degree of morbidity and mortality mainly due to infections and the occurrence of graft-versus-host disease (GVHD) . Therefore, the initial risk stratification assessment is becoming more important in deciding whether a patient should be a candidate for allo-HCT.
In addition to conventional cytogenetics, the results from nucleophosmin (
Accordingly, the present study used a retrospective analysis to evaluate the effect of allo-HCT on the long-term outcomes of newly diagnosed AML patients with
In this study, we retrospectively investigated 88 patients newly diagnosed with AML and who had received intensive induction chemotherapy at Kyungpook National University Hospital (KNUH) from March 2015 to July 2017. The other selection criteria included the presence of results regarding genetic abnormalities including
Bone marrow and blood samples for cytogenetic and molecular analyses were obtained at the time of the initial diagnosis. The cytogenetic studies on pretreated bone marrow were performed at the time of diagnosis using unstimulated short-term (24-hour) cultures with standard G-banding. The karyotypes were interpreted using the International System for Cytogenetic Nomenclature (ISCN) criteria . All molecular analyses (fluorescence
All patients received a standard induction chemotherapy, which consisted of idarubicin (at a dose of 12 mg per square meter of body-surface area per day, administered by intravenous injection on days 1, 2, and 3) and cytarabine (at a dose of 200 mg per square meter, administered by continuous intravenous infusion on days 1 through 7). Those patients who achieved complete remission after induction chemotherapy received a consolidation therapy with a high dose of cytarabine (at a dose of 3.0 g per square meter, administered over a period of 3 hours every 12 hours on days 1, 3, and 5). Patients classified as high- and intermediate-risk were recommended to receive allo-HCT, while low-risk patients completed their treatment with three cycles of consolidation. The patients who underwent allo-HCT received a myeloablative conditioning (MAC, busulfan at a dose of 3.2 mg per kilogram for 4 days, plus fludarabine at 30 mg per square meter of body-surface area for 6 days) regimen or reduced intensity conditioning (RIC, busulfan at a dose of 3.2 mg per kilogram for 2 days, plus fludarabine at the same dose for 6 days) regimen according to comorbidities and the condition of the patient.
The descriptive statistics are reported as proportions and medians. Overall survival (OS) and leukemia-free survival (LFS) were calculated from the date of diagnosis to death from any cause and relapse or death from any cause, respectively. To address the time dependence of the allo-HCT, the Simon and Makuch method was used in the graphical representation and the Mantel-Byar test for the univariate analysis. Cox's regression model was used according to the method of Andersen and Gill for identifying factors for long-term survival. Factors with a
The median age of the 88 patients included in this study was 53 years (range, 21–69 yr), and 49 patients (56%) were men.
Following induction chemotherapy, 63 patients (72%) achieved a complete response (CR), whereas 25 patients (28%) experienced primary refractory disease. According to the ENL risk groups, the CR rates for the favorable, intermediate, and adverse risk groups were 92% (N=23/25), 66% (N=29/44), and 58% (N=11/19), respectively (
The median follow-up duration was 12.9 months (range, 1.3–39.0 mo). The 1-year OS rates were 100%, 83.5±6.9%, and 56.1±12.8% in the favorable, intermediate, and adverse risk group, respectively (
In the univariate analysis, an adverse cytogenetic risk [hazard ratio (HR), 6.28;
In the univariate analysis, a high
Among the 40
The current study evaluated the clinical outcomes for intermediate-risk AML patients with
Furthermore, for the favorable-risk group, the current study found an improved long-term OS rate over the RFS rate, reflecting the positive role of salvage therapies, including allo-HCT (Fig. 2C, D). In contrast, the long-term OS rate for the intermediate-risk
The prognosis for AML depends on various patient-related factors, especially age and comorbidities, plus disease-related factors, such as chromosomal aberrations, genetic mutations, and the achievement of CR. The present study also confirmed the importance of achieving CR on patient outcomes for AML (Supplementary Table 1). While the long-term survival rates were similar for the ELN favorable-risk group and intermediate-risk
Although the present data did not indicate a significant predictive role of allo-HCT for intermediate-risk
In conclusion, the current study showed similar OS rates for the intermediate-risk
Response rates according to the ENL risk group.
Overall survival rates of