According to the latest National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML), either the 1, 3, and 5 day of high-dose cytarabine (HIDAC-135) or 1, 2, and 3 day of HIDAC (HIDAC-123) are recommended dosing regimens. Only one study was referenced, suggesting no difference in hematologic toxicity or survival between the two regimens in adult patients with AML (see Table 1). [1]
One review article, published in 2021, examined the optimal dosing of cytarabine during post-remission therapy for AML. Cytarabine dosing is generally categorized as standard (100–200 mg/m²), intermediate (400-1500 mg/m²), or high (>2000 mg/m²). Early trials comparing these doses were primarily conducted in the post-remission (consolidation) setting following standard 7+3 induction therapy. Notably, the Cancer and Leukemia Group B (CALGB)/Alliance trial from 1994 popularized the HiDAC-135 schedule (3 g/m² twice daily on days 1, 3, and 5); however, subsequent analyses from German and French studies demonstrated that the alternative HiDAC-123 schedule (3 g/m² twice daily on days 1, 2, and 3) provides equivalent anti-leukemia efficacy. HiDAC-123 was associated with faster hematologic recovery, fewer infections, reduced transfusion requirements, and shorter hospital stays, with no difference in relapse-free or overall survival compared with HiDAC-135. Although these results are largely retrospective, the review concluded that HiDAC-123 should be considered the preferred regimen for administering higher-dose cytarabine in post-remission therapy following standard induction. [2], [3], [4], [5]
A 2023 presentation abstract describes a study which evaluated a condensed, three-day schedule (AC123) for administering cytarabine consolidation therapy in Acute Myeloid Leukemia (AML) and compared it to the standard five-day schedule (AC135). While the condensed schedule's efficacy had been established in patients under 60, this research specifically investigated its use in older adults. The findings demonstrated that the AC123 regimen was safe and resulted in a statistically significant faster recovery of neutrophils and platelets (p<0.05) for patients both over and under 60 years of age, without an increase in complications such as hospitalization rates (p= 0.1), fever rate (p= 0.3), infection (p= 0.2), bacteremia (p= 0.4) and bleeding requiring intervention (p= 0.4). Based on these results, the authors concluded that the condensed three-day schedule should be considered the preferred method for consolidation therapy administration. [6]
A 2022 abstract described a retrospective and prospective study comparing HiDAC-135 (days 1, 3, and 5) and HiDAC-123 (days 1, 2, and 3) used as consolidation therapy for adults with acute myeloid leukemia (AML). The study aimed to evaluate whether HiDAC-123 could shorten hospitalization and reduce transfusion needs. Patients aged 18 years or older (excluding those with acute promyelocytic leukemia) were included, with historical data analyzed for HiDAC-135 and prospective data collected for HiDAC-123. Between January 2020 and May 2022, 30 HiDAC-135 and 28 HiDAC-123 cycles were administered. Baseline characteristics, including cytogenetic and molecular profiles, were similar between groups. The median hospital stay was 5 days for HiDAC-123 and 7 days for HiDAC-135, a difference that was not statistically significant. The proportion of patients hospitalized for ≤10 days was higher with HiDAC-123 (86% vs. 70%), but again not statistically significant. Readmission rates and causes, mainly thrombocytopenia, febrile neutropenia, and anemia, were comparable between groups. Notably, transfusion requirements during elective admission were significantly lower with HiDAC-123 (3.6% vs. 20%; p= 0.05), though transfusion rates during readmission did not differ. The authors concluded that HiDAC-123 may modestly reduce transfusion needs during elective admissions but does not significantly affect readmission rates, hospitalization duration, or cytopenia incidence. They also noted that the small sample size limited statistical power and that larger studies are warranted to confirm these findings. [7]