Purpose: L-ascorbic acid (LAA) modifies the in vitro growth of leukemic cells from approximately 50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498). Experimental results: During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An in vitro assay was performed pre-therapy for LAA sensitivity of leukemic cells from individual patients. Results: Of 18 patients enrolled, 8 of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (4 patients) as well as during supplementation (5 patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the in vitro assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared to none of six patients that were insensitive to LAA. Conclusions: The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.

The aim of this study was to assess the effect of acupressure, applied at P6 (Neiguan) acupuncture point, on chemotherapy-induced nausea and vomiting in patients with acute myeloblastic leukemia. This was a randomized controlled trial conducted on patients with myeloblastic leukemia. A total of 90 patients, who received the same chemotherapy regimen and antiemetic therapy, were included in the study as 30 patients in the control group, 30 patients in the band group, and 30 patients in the pressure group. Although acupressure was applied by placing wristbands at P6 acupuncture point of both wrists in patients of the band group for totally 4 days, acupressure was applied with the use of finger pressure in patients of the pressure group for totally 4 days. No intervention was made in patients of the control group other than the routine antiemetic therapy. The data of the study were collected by using a questionnaire and nausea-vomiting chart. Severity of nausea-vomiting was assessed by using the visual analog scale on this chart. It was determined that the acupressure band applied to the patients included in the study reduced number and severity of nausea-vomiting (P<.05); however, the acupressure applied with pressure did not affect number and severity of nausea-vomiting (P>.05). It was found that the acupressure band was effective for reducing the chemotherapy-induced nausea and vomiting.

BACKGROUND:Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic.

METHODS:The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment.

RESULTS:We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug-alone treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC.

CONCLUSION:On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML.

Extracellular stimuli signal for activation of the transcription factor NFkappaB, leading to gene expression regulating processes involved in immune responses, inflammation, and cell survival. Tumor necrosis factor-alpha (TNFalpha) activates NFkappaB via a well-defined kinase pathways involving NFkappaB-inducing kinase (NIK), which activates downstream multisubunit IkappaB kinases (IKK). IKK in turn phosphorylates IkappaB, the central regulator of NFkappaB function. We found that intracellular vitamin C inhibits TNFalpha-induced activation of NFkappaB in human cell lines (HeLa, monocytic U937, myeloid leukemia HL-60, and breast MCF7) and primary endothelial cells (HUVEC) in a dose-dependent manner. Vitamin C is an important antioxidant, and most cells accumulate ascorbic acid (AA) intracellularly by transporting the oxidized form of the vitamin, dehydroascorbic acid (DHA). Because ascorbic acid is a strong pro-oxidant in the presence of transition metals in vitro, we loaded cells with vitamin C by incubating them with DHA. Vitamin C-loaded cells showed significantly decreased TNFalpha-induced nuclear translocation of NFkappaB, NFkappaB-dependent reporter transcription, and IkappaBalpha phosphorylation. Our data point to a mechanism of vitamin C suppression of NFkappaB activation by inhibiting TNFalpha-induced activation of NIK and IKKbeta kinases independent of p38 MAP kinase. These results suggest that intracellular vitamin C can influence inflammatory, neoplastic, and apoptotic processes via inhibition of NFkappaB activation.