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. 2023 Nov 28;7(22):6886-6897.
doi: 10.1182/bloodadvances.2023010559.

Vitamin C and D supplementation in acute myeloid leukemia

Pierre Luc Mouchel  1   2   3 , Emilie Bérard  4   5 , Suzanne Tavitian  1 , Noémie Gadaud  1 , François Vergez  2   3   6 , Jean Baptiste Rieu  6 , Isabelle Luquet  6 , Audrey Sarry  1 , Françoise Huguet  1 , Laetitia Largeaud  6 , Eric Delabesse  2   3   6 , Anne Huynh  1 , Sarah Bertoli  1   2   3 , Christian Récher  1   2   3
Affiliations

Vitamin C and D supplementation in acute myeloid leukemia

Pierre Luc Mouchel et al. Blood Adv. .

Abstract

Recent studies have highlighted the role of vitamin C and D in acute myeloid leukemia (AML). In 2018, we changed our practices to add both vitamins to the supportive care for all consecutive patients with AML undergoing intensive chemotherapy. In this study, we compared the outcomes of patients treated before and after this change in practice. From 2015 to 2020, 431 patients were included, 262 of whom received no supplementation and 169 of whom received vitamin supplementation. Vitamin C and vitamin D was administered from day 10 of chemotherapy until hematologic recovery from induction and consolidation. Most patients presented at diagnosis with low levels of vitamin C and D. Upon recovery from induction, vitamin D levels among the vitamin C/D group significantly increased compared with those at diagnosis, and pretransplant levels were significantly higher in the vitamin C/D group compared with the control group (median of 33 vs 19 ng/mL; P < .0001). During induction, the rates of bacterial or fungal infection, hemorrhage, or macrophage activation syndrome were lower in the vitamin C/D group, whereas there was no difference in response rate, relapse incidence, and overall survival (OS). However, the multivariate analysis for OS showed a significant interaction between vitamin C/D and NPM1 mutation, meaning that vitamin C/D supplementation was significantly and independently associated with better OS in patients with NPM1 mutations (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.30-0.90; P = .019) compared with patients with wild-type NPM1 (HR, 1.01; 95% CI, 0.68-1.51; P = .95). In conclusion, vitamin C/D supplementation is safe and could influence the outcomes of patients with AML undergoing intensive chemotherapy.

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Conflict of interest statement

Conflict-of-interest disclosure: C.R. reports receiving research grants (to institution) from AbbVie, Astellas, Bristol Myers Squibb, Jazz Pharmaceuticals, IQVIA; and serves on advisory boards of AbbVie, Astellas, Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Servier, Takeda. S.B. serves in an advisory role for AbbVie, Jazz Pharmaceuticals, Daiichi-Sankyo, Sanofi, Astellas, and Bristol Myers Squibb. F.V. received research grants from Pierre Fabre and Roche; and serves as an adviser for Astellas and Amgen. F.H. reports consultancy for Novartis, Pfizer, and Incyte; and received honoraria from Amgen and Servier. I.L. serves in an advisory role for Jazz Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Vitamin levels at diagnosis and at end of induction chemotherapy in patients of the vitamin C/D supplementation group. (A) Vitamin C levels in mg/L. (B) Vitamin D levels in ng/mL.
Figure 2.
Figure 2.
Survival curves in patients of the control and vitamin C/D groups. (A) EFS. Control group: 1-year EFS, 59% (95% CI, 53-65); 3-year EFS, 36% (95% CI, 30-42); 5-year EFS, 32% (95% CI, 26-38). Vit C/D group: 1-year EFS, 57% (95% CI, 53-62); 3-year EFS, 34% (95% CI, 29-38); 5-year EFS, not estimated. (B) RFS. Control group: 1-year RFS, 64% (95% CI, 57-70); 3-year RFS, 41% (95% CI, 35-48); 5-year RFS, 37% (95% CI, 31-44). Vitamin C/D group: 1-year RFS, 58% (95% CI, 50-66); 3-year RFS, 37% (95% CI, 27-46); 5-year RFS, not estimated. (C) CIR. Control group: 1-year CIR, 34% (95% CI, 29-39); 3-year CIR, 52% (95% CI, 47-57); 5-year CIR, 54% (95% CI, 48-60). Vitamin C/D group: 1-year CIR, 34% (95% CI, 29-39); 3-year CIR, 50% (95% CI, 45-56); 5-year CIR, not estimated. (D) OS. Control group: 1-year OS, 72% (95% CI, 66-77); 3-year OS, 49% (95% CI, 43-55); 5-year OS, 39% (95% CI, 33-46). Vitamin C/D group: 1-year OS, 73% (95% CI, 66-79); 3-year OS, 47% (95% CI, 38-56); 5-year OS, not estimated.
Figure 3.
Figure 3.
OS curves in patients of the control and vitamin C/D groups with or without NPM1 mutations. (A) OS in NPM1 mutated patients. (B) OS in NPM1 wild-type patients.
See this image and copyright information in PMC

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