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Cancer Management and Research Volume 11, 2019 - Issue
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Original Research

Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 

Yan Huang1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Juan Hu1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Ting Lu1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Yi Luo1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Jimin Shi1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Wenjun Wu1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Xiaoyan Han1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Weiyan Zheng1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Jingsong He1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Zhen Cai1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Guoqing Wei1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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He Huang1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
&
Jie Sun1 Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;2 Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;3 Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China;4 Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of ChinaCorrespondence[email protected] [email protected]
 show all
Pages 4129-4142 | Published online: 08 May 2019

Figures & data

Table 1 Patients’ characteristics

Figure 1 Prognostic analysis of all 76 patients. (A) Overall survival of all 76 AMLFLT3-ITD+/NPM1+ patients. (B) Disease-free survival of all 76 AMLFLT3-ITD+/NPM1+ patients.

Abbreviations: OS, overall survival; DFS, disease-free survival.

Figure 1 Prognostic analysis of all 76 patients. (A) Overall survival of all 76 AMLFLT3-ITD+/NPM1+ patients. (B) Disease-free survival of all 76 AMLFLT3-ITD+/NPM1+ patients.Abbreviations: OS, overall survival; DFS, disease-free survival.

Figure 2 Comparison of chemotherapy and allo-HSCT in patients received CR1. (A, B): OS and DFS of the 53 AMLFLT3-ITD+/NPM1+ patients received CR1. (C, D) OS and DFS of the 44 AMLFLT3ITD+/NPM1+patients (age<60 years) received CR1.

Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy; CR1, first complete remission.

Figure 2 Comparison of chemotherapy and allo-HSCT in patients received CR1. (A, B): OS and DFS of the 53 AMLFLT3-ITD+/NPM1+ patients received CR1. (C, D) OS and DFS of the 44 AMLFLT3ITD+/NPM1+patients (age<60 years) received CR1.Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy; CR1, first complete remission.

Figure 3 Comparison of outcome in different mutation groups. (A, B) OS and DFS of AMLFLT3-ITD+/NPM1+/DNMT3A R882+vs. AMLFLT3-ITD+/NPM1+/DNMT3A R882-in 61 patients. (C, D) Comparison of the survival of chemotherapy group and allo-HSCT group in 18 AMLFLT3-ITD+/NPM1+/DNMT3A R882+ patients. (E, F) Comparison of the survival of chemotherapy group and allo-HSCT group in 43 AMLFLT3ITD+/NPM1+/DNMT3A R882-patients.

Abbreviations: OS, overall survival; DFS, disease-free survival; pos, positive; neg, negative; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy.

Figure 3 Comparison of outcome in different mutation groups. (A, B) OS and DFS of AMLFLT3-ITD+/NPM1+/DNMT3A R882+vs. AMLFLT3-ITD+/NPM1+/DNMT3A R882-in 61 patients. (C, D) Comparison of the survival of chemotherapy group and allo-HSCT group in 18 AMLFLT3-ITD+/NPM1+/DNMT3A R882+ patients. (E, F) Comparison of the survival of chemotherapy group and allo-HSCT group in 43 AMLFLT3ITD+/NPM1+/DNMT3A R882-patients.Abbreviations: OS, overall survival; DFS, disease-free survival; pos, positive; neg, negative; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy.

Figure 4 Comparison of outcome in different clinical groups associated with HL. (A, B) OS and DFS of HL vs. non-HL in all 76 patients. (C, D) Comparison the survival of chemotherapy group and allo-HSCT group in 28 patients with HL. (E, F) Comparison the survival of chemotherapy group and allo-HSCT group in 48 patients with non-HL.

Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy; HL, hyperleukocytosis.

Figure 4 Comparison of outcome in different clinical groups associated with HL. (A, B) OS and DFS of HL vs. non-HL in all 76 patients. (C, D) Comparison the survival of chemotherapy group and allo-HSCT group in 28 patients with HL. (E, F) Comparison the survival of chemotherapy group and allo-HSCT group in 48 patients with non-HL.Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy; HL, hyperleukocytosis.

Figure 5 Comparison of relapse rate in different biological and clinical groups. (A) CI of relapse between AMLFLT3-ITD+/NPM1+/DNMT3A R882+and AMLFLT3-ITD+/NPM1+/DNMT3A R882-in 49 patients received CR (P=0.009). (B) CI of relapse between HL and Non-HL in 53 patients received CR (P=0.371).

Abbreviations: CI, cumulative incidence; HL, hyperleukocytosis; CR, complete remission.

Figure 5 Comparison of relapse rate in different biological and clinical groups. (A) CI of relapse between AMLFLT3-ITD+/NPM1+/DNMT3A R882+and AMLFLT3-ITD+/NPM1+/DNMT3A R882-in 49 patients received CR (P=0.009). (B) CI of relapse between HL and Non-HL in 53 patients received CR (P=0.371).Abbreviations: CI, cumulative incidence; HL, hyperleukocytosis; CR, complete remission.

Table 2 Analysis of risk factors of FLT3-ITD and NPM1 double mutated AML

Table 3 Multivariate Cox model analysis of FLT3-ITD and NPM1 double mutated AML

Figure 6 Comparison of chemotherapy and allo-HSCT in AMLFLT3-ITD+/NPM1+patients without three risk factors including age ≥60, HL and DNMT3A R882 mutation. (A, B) OS and DFS of 24 AMLFLT3-ITD+/NPM1+/DNMT3A R882-patients younger than 60 years old and without HL.

Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy.

Figure 6 Comparison of chemotherapy and allo-HSCT in AMLFLT3-ITD+/NPM1+patients without three risk factors including age ≥60, HL and DNMT3A R882 mutation. (A, B) OS and DFS of 24 AMLFLT3-ITD+/NPM1+/DNMT3A R882-patients younger than 60 years old and without HL.Abbreviations: OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy.

Figure S1 Comparison of chemotherapy and allo-HSCT in AML FLT3-ITD+/NPM1+ patients received IA as induction regimen. (A, B) OS and DFS of all AML FLT3-ITD+/NPM1+ patients. (C,D) OS and DFS of the AML FLT3-ITD+/NPM1+ patients with age<60 years.

Abbreviations: IA, idarubicin and cytarabine; OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy;

Figure S1 Comparison of chemotherapy and allo-HSCT in AML FLT3-ITD+/NPM1+ patients received IA as induction regimen. (A, B) OS and DFS of all AML FLT3-ITD+/NPM1+ patients. (C,D) OS and DFS of the AML FLT3-ITD+/NPM1+ patients with age<60 years.Abbreviations: IA, idarubicin and cytarabine; OS, overall survival; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; chemo, chemotherapy;

Table S1 Biological and clinical characteristics

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