Patients with acute myeloid leukemia (AML) who received vitamin C and D supplements during intensive chemotherapy had lower rates of complications such as infections, bleeding, and inflammation compared with patients who did not receive the supplements, according to a recent study published by Mouchel et al in Blood Advances. Although these findings showed no difference in survival between the two groups, a subgroup analysis demonstrated the risk of mortality was nearly 50% lower among patients with NPM1 mutations who were taking the vitamin C and D supplements.
Background
NPM1 mutations are found in 30% to 35% of patients with AML.
Previous studies have suggested higher vitamin D levels prior to receiving a donor stem cell transplant may reduce the risk of posttransplant relapse in patients with AML, whereas others indicated vitamin C supplementation may suppress the development of leukemic cells.
“To the best of our knowledge, this is [one of] the first studies to examine the potential effects of vitamin C and D supplementation during intensive chemotherapy for AML,” explained senior study author Christian Récher, MD, of the University Cancer Institute of Toulouse, France. “We have shown that supplementation is feasible and safe and may help reduce some significant adverse events associated with intensive chemotherapy, which is a clear benefit for patients,” he added.
Study Methods and Results
In this study, researchers compared the outcomes of 431 patients with AML—169 received vitamin C and D supplements and 262 were controls—treated with intensive chemotherapy over a 5-year period.
The researchers noted that the patients in the supplementation group had a median age of 65 years, and 52% identified as female, whereas those in the control group had a median age of 60 years, and 53% identified as male. At the time of AML diagnosis, a majority of the patients in both groups had low vitamin C and D levels. About 25% of the patients in the supplementation group and about 33% of those in the control group went on to receive donor stem cell transplants. The median follow-up period was 28.7 months for the supplementation group and 58.2 months for the control group.
The researchers found that the patients who received the vitamin C and D supplements experienced increases in vitamin D levels from 18 ng/mL at diagnosis to 39 ng/mL at recovery from intensive chemotherapy—falling between the normal range of 20 ng/mL and 50 ng/mL for vitamin D levels. No significant increases were seen in vitamin C levels, potentially as a result of the conservative regimen of 6 g per week.
During intensive chemotherapy, the patients who received the supplements experienced lower rates of moderate-to-severe bacterial infections (27.2% vs 35.1%), bleeding (1.8% vs 5.7%), and potentially life-threatening immune system inflammation (1.8% vs 8.8%) compared with controls. The researchers also revealed that median overall survival was 34.5 months, median survival without a relapse was 20.6 months, and the cumulative incidence of relapse was 46.4%. They reported no statistically significant differences between the two groups after examining the outcomes for all treated patients combined. However, a subgroup analysis found the patients in the supplementation group who had NPM1 mutations experienced a 48% reduction in the risk of mortality compared with those who did not have the mutations.
Conclusions
Although the researchers were surprised by the improved survival rate in patients with NPM1 mutations who received vitamin C and D supplements, they cautioned that the association and the mechanism responsible for this survival difference may require confirmation in larger, randomized studies.
The researchers reviewed several limitations of this study—including that it was retrospective, conducted at a single institution, had a small number of patients, and compared outcomes for patients treated before and after the institution introduced supplementation for all adults undergoing intensive chemotherapy for AML. Additionally, because all patients in the supplementation group received both vitamin C and D, the researchers could not analyze the independent effect of each vitamin or the value of combining them.
“Our results are encouraging and support prospective clinical trials of vitamin C and D administration in [patients with] AML,” concluded Dr. Récher.
Patients were advised to review all over-the-counter drugs, vitamins, and dietary supplements with their physicians prior to initiating them.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
