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 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

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

Abstract Background The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. Methods We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. Results The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). Conclusions Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable

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