Conventional Versus Condensed Regimen of High Dose Cytarabine Consolidation in Acute Myeloid Leukemia

Background

Acute myeloid leukemia is a hematological malignancy that results from genetic mutations contributing to the production of undifferentiated myeloid precursors. To induce remission, induction chemotherapy is warranted followed by consolidation which consists of high dose cytarabine (HiDAC) given as 1-3 gm/m2. HiDAC requires three days of administration on days 1, 3 and 5 (HiDAC-135) and is considered the standard of care. Recently there has been a great interest in the exploration of HiDAC administered on days 1, 2 and 3 (HiDAC-123). We planned to assess the benefit of utilizing HiDAC-123 to reduce hospital days and need for transfusion.

Methods

A retrospective and prospective study that included adults aged ≥ 18 years and diagnosed with AML. Patients with APL are excluded from the study. We gathered the data by utilizing the hospital's health care system. Retrospectively, patients who received HiDAC-135 were considered the historical group, whereas patients who received HiDAC-123 were followed prospectively. The primary endpoints were the duration of admission and platelet or packed red blood cell transfusion. Secondary endpoints were the proportion of readmissions and incident of febrile neutropenia, thrombocytopenia and anemia during readmission. Comparison of medians was conducted by using the kolmogorov smirnov test and comparison of proportions was conducted by using Fisher Exact test.

Results

Between January 2020 and May 2022, A total of 30 and 28 cycles were given in the HiDAC-135 and HiDAC-123 groups, respectively. The mean age was 38.6 (±17.9) in the HiDAC-123 group and 39.1 (±18.4) in the HiDAC-135 group. The predominant cytogenetic finding was a normal cytogenetic profile (58.3% with HiDAC-123 and 53.8% with HiDAC-135). NPM1 was the most common molecular finding in both groups (25% with HiDAC-123 and 23% with HiDAC-135) (Table). The HiDAC dosing was between 1-3 gm/m2. The median duration of hospitalization was 5 days with HiDAC-123 and 7 days with HIDAC-135 (-15-14.6 95% CI, P=0.94). The duration of hospitalization ≤ 10 days was 86% with HiDAC-123 and 70% with HiDAC-135 (P=0.12). Readmission occurred in 64.3% with HiDAC-123 whereas 50% of readmission occurred with HiDAC-135 (P=0.06). Reasons for readmission were due to thrombocytopenia (88.8% with HiDAC-123 and 80% with HiDAC-135, P=0.19) followed by febrile neutropenia (83.3% with HiDAC-123 and 66.6% with HiDAC-135, P=0.12) and anemia (22.2% with HiDAC-123 and 40% with HiDAC-135, P=0.56). Transfusion during elective admission occurred with 20% of the patients who received HiDAC-135 and 3.6% with HiDAC-123 (P=0.05) and transfusion during readmission occurred 100% with HiDAC-135 and 83.3% with HiDAC-123 (P=0.53).

Conclusion

The results of our study suggest that the use of HiDAC-123 may reduce the need for transfusion during elective admission. However, the use of this protocol did not reduce the rate of readmission, duration of hospitalization and incident of pancytopenia. Our study is limited by the small sample size and thus large-scale studies are needed to further assess its impact on the duration of hospitalization and readmission.

No relevant conflicts of interest to declare.