Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study

Does high‐dose cytarabine cause cumulative toxicity in patients undergoing consolidation therapy for acute myeloid leukemia?

“…Although the studies we discuss here have significant differences in patient size (small or large), center number (single or multicenter), type of study (prospective or retrospective), and geographical place (Europe, USA, or Japan), these study results are remarkably consistent [4][5][6][7][8]. No study reported increased mortality by increased number of HiDAC cycles.…”

“…The number of platelet and red blood cell transfusions [5,7] and duration of thrombocytopenia [7] remained stable throughout the HiDAC cycles [5,7]. Documented fungal infections [8], empirical intravenous antifungal use [8], duration of antibiotic use [7], and the frequency of pneumonia [5] were similar between HiDAC cycles. No accumulated central nervous system, hepatic, or renal toxicity reported during HiDAC cycles [5,7].…”

“…No study reported increased mortality by increased number of HiDAC cycles. The frequency of neutropenic fever, the duration of neutropenia, and neutropenic fever were not increased by the HiDAC cycle number [5,7,8]. Rather, it has been described that the numbers of functionally active neutrophils (exhibiting anti-bacterial effects) often survive until day 10 or even 12 in HiDAC-treated patients [9].…”

“…No accumulated central nervous system, hepatic, or renal toxicity reported during HiDAC cycles [5,7]. Someone may argue that there is a decline in the number of patients from HiDAC cycle number 1 to HiDAC cycle 3 or 4, which reflects accumulative toxicity [4,6,7]. Although it could, the decline not only caused by toxicity, patient refusal, or dead in remission but also resulted from relapse and undergoing allogeneic hematopoietic cell transplantation (alloHCT).…”

“…Documented fungal infections [8], empirical intravenous antifungal use [8], duration of antibiotic use [7], and the frequency of pneumonia [5] were similar between HiDAC cycles. No accumulated central nervous system, hepatic, or renal toxicity reported during HiDAC cycles [5,7]. Someone may argue that there is a decline in the number of patients from HiDAC cycle number 1 to HiDAC cycle 3 or 4, which reflects accumulative toxicity [4,6,7].…”