High-Dose Cytarabine in Acute Myeloid Leukemia Treatment: A Systematic Review and Meta-Analysis

<div><p>The optimal dose, scheme, and clinical setting for Ara-C in acute myeloid leukemia (AML) treatment remain uncertain. In this study, we performed a meta-analysis to systematically assess the impact of high-dose cytarabine (HDAC) on AML therapy during the induction and consolidation stages. Twenty-two trials with a total of 5,945 <i>de</i><i>novo</i> AML patients were included in the meta-analysis. Only patients less than 60 year-old were included in the study. Using HDAC in induction therapy was beneficial for RFS (HR = 0.57; 95% CI, 0.35–0.93; <i>P</i> = 0.02) but not so for CR rate (HR = 1.01; 95% CI, 0.93–1.09; <i>P</i> = 0.88) and OS (HR = 0.83; 95% CI, 0.66–1.03; <i>P</i> = 0.1). In consolidation therapy, HDAC showed significant RFS benefits (HR = 0.67; 95% CI, 0.49–0.9; <i>P</i> = 0.008) especially for the favorable-risk group (HR = 0.38; 95% CI, 0.21–0.69; <i>P</i> = 0.001) compared with SDAC (standard dose cytarabine), although no OS advantage was observed (HR = 0.84; 95% CI, 0.55–1.27; <i>P</i> = 0.41). HDAC treatment seemed less effective than auto-BMT/allo-BMT treatment (HR = 1.66, 95% CI, 1.3–2.14; <i>P</i><0.0001) with similar OS. HDAC treatment led to lower relapse rate in induction and consolidation therapy than SDAC treatment, especially for the favorable-risk group. Auto-BMT/allo-BMT was more beneficial in prolonging RFS than HDAC.</p></div

Effect of HDAC versus SDAC in induction therapy.

<p><b>A</b>: Effect of HDAC versus SDAC in induction therapy on CR rate. <b>B</b>: Overall survival benefit of HDAC in induction therapy. <b>C</b>: Relapse free survival benefit of HDAC in induction therapy.</p

Relapse free survival benefit of HDAC in consolidation therapy.

<p><b>A</b>: Total relapse free survival benefit of HDAC in consolidation therapy. <b>B</b>: Relapse free survival benefit of different subgroups of HDAC in consolidation therapy.</p

Effect of HDAC versus BMT on overall survival.

<p>Effect of HDAC versus BMT on overall survival.</p

Characteristics of Included Studies for consolidation therapy.

<p>Note: ▴ S. Miyawaki et al, 2011 repeated the same trial of S, Ohtake et al, 2011.</p><p>BMT randomized trials were defined that if the patients didn’t have donors, they were randomized into auto-BMT and high-dosed Ara-C groups.</p><p>★analyze analyze <60 years the patients in each trial.</p><p>Abbreviations: NR, not reported; IDA, idarubicin; Ara-c, cytarabin; VP-16, etoposide; DNR, daunorubicin MCT, multiagent chemotherapy;</p><p>CTX, cyclophosphamide; MTZ, mitoxantrone; AZQ, diaziquone; 6-TG, thioguanine; AMS, amsacrine.</p><p>Characteristics of Included Studies for consolidation therapy.</p

Characteristics of included Studies for induction therapy.

<p>Note: ▴ T. Büchner et al, 2009 repeated the same trial of T. Büchner et al, 2006.</p><p>analyze <60 years patients in each trial.</p><p>Abbreviations: NR, not reported; IDA, idarubicin; Ara-c, cytarabin; VP-16, etoposide; DNR, daunorubicin.</p><p>Characteristics of included Studies for induction therapy.</p

Effect of HDAC versus BMT on relapse free survival.

<p>Effect of HDAC versus BMT on relapse free survival.</p

Additional file 1: of Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population

This file contains Tables S1–S7, including Table S1. CBF ratios in European, American, and Eastern Asian cohorts; Table S2. NPM1 mutation ratios in European and our cohorts; Table S3. FLT3-ITD mutation ratios in European and our cohorts; Table S4. FLT3-ITD mutation ratios in older patients from Chinese cohort against European and American cohorts; Table S5. CBF leukemia ratios in older patients from Japanese and Chinese cohorts against European and American cohorts; Table S6. NPM1 mutation ratios in older patients from Chinese cohort against European and American cohorts; and Table S7. Outcomes in European, American, and Eastern Asian cohorts. (PDF 568 kb

Additional file 2: Table S1. of An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification

The ratio of different cytogenetic risk category in different age group. The ratio of different cytogenetic risk category (intermediate and unfavorable risk) in <40, 40–60, >60 age group. (DOCX 12 kb

Additional file 3: of An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification

Raw data. The clinical characteristic of 97 previously diagnosed de novo adult acute erythroid leukemia patients. The clinical characteristic of 97 previously diagnosed de novo adult acute erythroid leukemia patients were listed, including MDS/AML subtype, MRC cytogenetic risk, survival data, gene mutation and so on. (DOC 239 kb