title: Depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes.
abstract: OBJECTIVE
  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 pretherapy for LAA sensitivity of leukemic cells from individual patients.
  
  
  RESULTS
  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 in vitro 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.
  
  
  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.
authors.affiliation: Cancer Center and Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. bkimler@kumc.edu
authors.forename: Chan H
authors.initials: CH
authors.lastname: Park
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.forename: Seong Yoon
authors.initials: SY
authors.lastname: Yi
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Eun Ryung
authors.initials: ER
authors.lastname: Lee
authors.forename: Miyong
authors.initials: M
authors.lastname: Rha
authors.forename: Seonwoo
authors.initials: S
authors.lastname: Kim
authors.forename: Mary H
authors.initials: MH
authors.lastname: Park
authors.forename: Sook J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hye K
authors.initials: HK
authors.lastname: Park
authors.forename: Mark H
authors.initials: MH
authors.lastname: Lee
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
authors.forename: Bong Seog
authors.initials: BS
authors.lastname: Kim
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D001205:Ascorbic Acid