Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

Jae-Ho Yoon; Hee-Je Kim; Dae-Hun Kwak; Gi June Min; Sung-Soo Park; Young-Woo Jeon; Sung-Eun Lee; Byung-Sik Cho; Ki-Seong Eom; Yoo-Jin Kim; Seok Lee; Chang-Ki Min; Seok-Goo Cho; Dong-Wook Kim; Jong Wook Lee; Woo-Sung Min

doi:10.5045/br.2017.52.3.174

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Original Article

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Blood Res 2017; 52(3):

Published online September 25, 2017

https://doi.org/10.5045/br.2017.52.3.174

Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

Jae-Ho Yoon, Hee-Je Kim, Dae-Hun Kwak, Gi June Min, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, and Woo-Sung Min^*

Author Info. +

Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Correspondence to : Woo-Sung Min, M.D., Ph.D. Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul 06591, Korea. wsmin@catholic.ac.kr

Received: March 18, 2017; Revised: April 3, 2017; Accepted: June 15, 2017

Abstract

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Abstract

Background

Standard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown.

Methods

We analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5?20% and >20% on day 7 of 3+7, respectively.

Results

Early intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11?3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55?0.93, P=0.012).

Conclusion

Early intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.

Keywords Acute myeloid leukemia, Induction chemotherapy, Early intensification

Article

Original Article

Blood Res 2017; 52(3): 174-183

Published online September 25, 2017 https://doi.org/10.5045/br.2017.52.3.174

Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

Correspondence to:Woo-Sung Min, M.D., Ph.D. Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul 06591, Korea. wsmin@catholic.ac.kr

Received: March 18, 2017; Revised: April 3, 2017; Accepted: June 15, 2017

Abstract

Background

Methods

Results

Conclusion

Keywords: Acute myeloid leukemia, Induction chemotherapy, Early intensification

Abstract

Fig 1.

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Figure 1.

Treatment strategy for adult patients with acute myeloid leukemia (AML) at the Catholic Blood and Marrow Transplantation Center in Korea. Abbreviations: BHAC, N⁴-behenoyl-1-β-D-arabinofburanosyl cytosine; CR, complete remission; D7BM, bone marrow blast evaluation on day 7 of chemotherapy; HCT, hematopoietic cell transplantation; MSD, matched sibling donor; MTZ, mitoxantrone; URD, unrelated donor.

Blood Research 2017; 52: 174-183https://doi.org/10.5045/br.2017.52.3.174

Fig 2.

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Figure 2.

Early treatment outcomes according to the intensity of induction chemotherapy. (A) Early death rates. (B) Early relapse rates before hematopoietic cell transplantation (HCT). (C) Early death rate among elderly patients (older than 55 yr). (D) Early relapse rate before HCT among patients younger than 55 years.

Blood Research 2017; 52: 174-183https://doi.org/10.5045/br.2017.52.3.174

Fig 3.

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Figure 3.

Overall survival (OS) and overall relapse rates according to the intensity of induction chemotherapy. (A) OS. (B) Overall cumulative incidence of relapse. (C) OS in the elderly patients (older than 55 yr). (D) OS in patients younger than 55 years.

Blood Research 2017; 52: 174-183https://doi.org/10.5045/br.2017.52.3.174

Table 1 . Baseline characteristics according to the intensity of induction chemotherapy..

^a)P<0.05..

Abbreviations: APM, acute panmyelosis with myelofibrosis; ARA-C, cytarabine; BHAC, N⁴-behenoyl-1-β-D-arabinofuranosyl cytosine; BM, bone marrow; HCT, hematopoietic cell transplantation; MRC, myelodysplasia-related change; NOS, not otherwise specified; PB, peripheral blood..

Table 2 . Early treatment outcomes according to the intensity of induction treatment..

^a)P<0.05. ^b)Early death from any cause (with or without aplasia) within 56 days after chemotherapy..

Abbreviations: Allo, allogeneic; Auto, autologous; BM, bone marrow; CR, complete remission; CTx, chemotherapy; HCT, hematopoietic cell transplantation..

Table 3 . Multivariate analysis to identify the factors affecting early treatment outcomes and OS..

^a)P<0.05..

Abbreviations: CTx, chemotherapy; HCT, hematopoietic cell transplantation; HR, hazard ratio..