Depletion of <small>L</small>-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes

다국어 초록 (Multilingual Abstract)

<P>Abstract</P><P>Purpose: </P><P><SMALL>L</SMALL>-ascorbic acid (LAA) modifies the <I>in vitro</I> growth of leukemic cells from ∼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).</P><P>Experimental results: </P><P>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 <I>in vitro</I> assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients.</P><P>Results: </P><P>Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the <I>in vitro</I> assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA.</P><P>Conclusions: </P><P>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.</P>