Blood Res.  2019 Sep;54(3):189-197. 10.5045/br.2019.54.3.189.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD

• Baek DW
• Lee JM
• Kim JH
• Cho HJ
• Ham JY
• Suh JS
• Sohn SK
• Moon JH

• KMID: 2459384
• DOI: http://doi.org/10.5045/br.2019.54.3.189

Abstract

BACKGROUND
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 (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated.
METHODS
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 NPM1 and FLT3-ITD.
RESULTS
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 NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML.
CONCLUSION
Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.

Keyword

Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; NPM1; FLT3-ITD

MeSH Terms

Cell Transplantation*
Classification
Consolidation Chemotherapy*
Gyeongsangbuk-do
Humans
Induction Chemotherapy
Leukemia, Myeloid, Acute*
Multivariate Analysis
Patient Selection
Protein-Tyrosine Kinases
Retrospective Studies
Transplants*
Protein-Tyrosine Kinases

Figure

• 

  Fig. 1 Response rates according to the ENL risk group.

• 

  Fig. 2 (A) One-year overall survival (OS) rate was 100%, 83.5±6.9%, 56.1±12.8% in favorable, intermediate, and adverse risk group, respectively. (B) One-year leukemia-free survival (LFS) rate was 91.7±5.6%, 77.0±6.8%, and 43.8±12.8% in favorable, intermediate, and adverse risk group, respectively. In patients with intermediate risk NPM1wt/FLT3-ITDneg/low, (C) one-year OS rate was 87.9±5.8%, and (D) one-year LFS rate was 75.6±7.7%, which were comparable to favorable risk group.

• 

  Fig. 3 Overall survival rates of NPM1wt/FLT3-ITDneg/low group according to the post-remission therapy.

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