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

Dong Won Baek; Jung Min Lee; Ju-Hyung Kim; Hee Jeong Cho; Ji-Yeon Ham; Jang-Soo Suh; Sang-Kyun Sohn; Joon Ho Moon

doi:10.5045/br.2019.54.3.189

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Original Article

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Blood Res 2019; 54(3):

Published online September 30, 2019

https://doi.org/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

Dong Won Baek^1#, Jung Min Lee^1#, Ju-Hyung Kim¹, Hee Jeong Cho¹, Ji-Yeon Ham², Jang-Soo Suh², Sang-Kyun Sohn¹, Joon Ho Moon¹

Author Info. +

Departments of ¹Hematology/Oncology and ²Laboratory Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence to : Joon Ho Moon, M.D., Ph.D.
Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea
E-mail: jhmoon@knu.ac.kr

Received: April 23, 2019; Revised: June 9, 2019; Accepted: June 20, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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-ITD^neg/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.

Keywords Acute myeloid leukemia, Allogeneic hematopoietic cell transplantation, NPM1, FLT3-ITD

Article

Original Article

Blood Res 2019; 54(3): 189-197

Published online September 30, 2019 https://doi.org/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

Dong Won Baek^1#, Jung Min Lee^1#, Ju-Hyung Kim¹, Hee Jeong Cho¹, Ji-Yeon Ham², Jang-Soo Suh², Sang-Kyun Sohn¹, Joon Ho Moon¹

Departments of ¹Hematology/Oncology and ²Laboratory Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence to:Joon Ho Moon, M.D., Ph.D.
Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea
E-mail: jhmoon@knu.ac.kr

Received: April 23, 2019; Revised: June 9, 2019; Accepted: June 20, 2019

Abstract

Background

Methods

Results

Conclusion

Keywords: Acute myeloid leukemia, Allogeneic hematopoietic cell transplantation, NPM1, FLT3-ITD

Abstract

Fig 1.

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Figure 1.

Response rates according to the ENL risk group.

Blood Research 2019; 54: 189-197https://doi.org/10.5045/br.2019.54.3.189

Fig 2.

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Figure 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 NPM1^wt/FLT3-ITD^neg/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.

Blood Research 2019; 54: 189-197https://doi.org/10.5045/br.2019.54.3.189

Fig 3.

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Figure 3.

Overall survival rates of NPM1^wt/FLT3-ITD^neg/low group according to the post-remission therapy.

Blood Research 2019; 54: 189-197https://doi.org/10.5045/br.2019.54.3.189

Patient characteristics.

Abbreviations: BM, bone marrow; CEBPA, CCAAT/enhancer binding protein α ELN, European LeukemiaNet; FLT3-ITD, fms-like tyrosine kinase 3-internal tandem duplication; Hb, hemoglobin; HCT, hematopoietic cell transplantation; NPM1, nucleophosmin 1; WBC, white blood cell..

Multivariate analysis.

Abbreviations: CI, confidence interval; ELN, European LeukemiaNet; FLT3-ITD, fms-like tyrosine kinase 3-internal tandem duplication; HR, hazard ratio; INT, intermediate; NPM1, nucleophosmin 1..