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[Preprint]. 2023 Dec 25:2023.10.24.23297165.
doi: 10.1101/2023.10.24.23297165.

INTRAVENOUS VITAMIN C SUPPLEMENTATION IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS: SALUTARY IMPACT ON CLINICAL OUTCOMES

Gary Simmons  1 , Roy Sabo  2 , May Aziz  3 , Erika Martin  3 , Robyn J Bernard  4 , Manjari Sriparna  4 , Cody McIntire  4 , Elizabeth Krieger  5 , Donald F Brophy  3 , Ramesh Natarajan  1 , Alpha Fowler 3rd  1 , Catherine H Roberts  6 , Amir Toor  1   7
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INTRAVENOUS VITAMIN C SUPPLEMENTATION IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS: SALUTARY IMPACT ON CLINICAL OUTCOMES

Gary Simmons et al. medRxiv. .

Update in

Abstract

Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (SCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic hematopoietic stem cell transplant (HSCT) were evaluated in a phase I/II trial and clinical outcomes compared with a propensity score - matched historical control.

Methods: Patients with advanced hematologic malignancies were enrolled in a phase 2 clinical trial, receiving IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HSCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT.

Results: 55 patients received IV vitamin C: these include 10/10 HLA-MRD and MUD (n=48) and 9/10 HLA MUD recipients (n=7). All patients enrolled were deficient in vitamin C at day 0 and had restoration to normal levels for the remainder of the course. Vitamin C recipients had lower non-relapse mortality (11% vs. 25%, p-value = 0.07) and consequently, improved survival compared to historical controls (82% vs 62% p=0.06), with no attributable grade 3 and 4 toxicities to vitamin C. Patients with myeloid malignancies had improved survival (83% vs. 54%, p=0.02) and non-relapse mortality (NRM) (10% vs. 37%, p=0.009), as well as chronic GVHD, with similar relapse rates compared to controls.

Conclusions: In patients undergoing allogeneic HSCT the administration of IV vitamin C is safe and reduces non-relapse mortality improving overall survival. Randomized trials are needed to confirm the utility of this easily available and inexpensive therapy.

Keywords: Graph analysis; Parenteral ascorbic acid; allogeneic stem cell transplantation; graft vs. host disease; non-relapse mortality.

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Figures

Figure 1.
Figure 1.
Graph depicting sequential outcomes in vitamin C recipients and historical controls following transplant. First tier clinical outcomes include GVHD and relapse, transient states which lead to clinical outcomes, survival, and mortality depicted in second tier nodes.
Figure 2.
Figure 2.
(A) CI curves depicting lower NRM in the VC treated patient. (B) In a multivariate model this was not significant (HR = 0.4, 95% CI: 0.1, 1.0, p-value = 0.069).
Figure 3.
Figure 3.
(A) KM curves depicting improved survival in the VC treated patients (p= 0.057). (B) In a multivariate model, only donor type (MUD vs. MRD: HR = 3.3, 95% CI: 1.1, 10.0, p = 0.032) and diagnosis (AML vs. ALL: HR = 7.75, 95% CI: 1.2, 50.2, p = 0.031) were significant.
Figure 4.
Figure 4.
Graph depicting sequential outcomes in vitamin C recipients and historical controls with myeloid malignancy following transplant. First tier clinical outcomes include GVHD and relapse, transient states which lead to clinical outcomes, survival, and mortality depicted in second tier nodes.
Figure 5.
Figure 5.
(A) KM curves depicting improved survival in the VC treated patients with myeloid malignancies (p= 0.0167). (B) In a multivariate model this relationship remained significant (HR = 0.32, 95% CI: 0.12, 0.84, p-value = 0.02) amongst myeloid malignancy patient.
Figure 6.
Figure 6.
(A) CI curves depicting lower NRM in the VC treated patients with myeloid malignancies. (B) In a multivariate model this was significant (HR = 0.22, 95% CI: 0.07, 0.69, p-value = 0.009).
Figure 7.
Figure 7.
(A) Vitamin C levels in the entire cohort of patients. (B) CRP levels at the same time points.
See this image and copyright information in PMC

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