Blood Res.  2017 Sep;52(3):174-183. 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

Affiliations
  • 1Department 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. wsmin@catholic.ac.kr

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.

Keyword

Acute myeloid leukemia; Induction chemotherapy; Early intensification

MeSH Terms

Adult*
Aged
Bone Marrow
Cytarabine
Drug Therapy*
Humans
Idarubicin
Induction Chemotherapy*
Leukemia, Myeloid, Acute*
Mortality
Multivariate Analysis
Recurrence
Remission Induction
Cytarabine
Idarubicin

Figure

  • Fig. 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.

  • Fig. 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.

  • Fig. 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.


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