menatetrenone and Anemia--Refractory

Vitamin K2 induces differentiation of leukemic cell lines and apoptosis of immature blasts in myelodysplastic syndrome (MDS). We recently reported a case of MDS-refractory anemia (MDS-RA) with trilineage hematologic response to oral administration of menatetrenone, a vitamin K2 analog. To determine a possible role of this agent in treatment of MDS-RA, we conducted a prospective randomized trial assessing the safety and efficacy of menatetrenone. A total of 18 consecutive patients newly diagnosed with MDS-RA were randomized to receive either 45 mg of oral menatetrenone (group 1) or no menatetrenone (group 2). Administration of menatetrenone was well tolerated. Of the nine patients in group 1 (56%), five improved with menatetrenone treatment while only one (11%) of the group 2 patients improved. Three patients (33%) showed a major response in absolute neutrophil count (ANC), two (22%) showed a major response in hemoglobin concentration, and two of the nine (22%) showed a major response in platelet count. The ANC of group 1 patients rose after treatment, while that of group 2 patients decreased slightly at follow-up after 16 weeks ( p=0.03). Significant improvement was also seen in final platelet count ( p=0.01), but not in hemoglobin concentration. Given the absence of toxicity, menatetrenone can be recommended for all patients with MDS-RA.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia, Refractory; Cell Count; Female; Hematopoiesis; Hemostatics; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Vitamin K 2

Although vitamin K2 is an inducer of the in vitro differentiation of myeloid leukemic cell lines, its clinical efficacy in the treatment of myelodysplastic syndrome (MDS) is unclear. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to an 80-year-old woman with MDS (refractory anemia) heavily dependent on red-cell transfusions. The patient's pancytopenia gradually improved, and she became transfusion-independent after 14 months. Pancytopenia recurred when menatetrenone was discontinued but recovered again with readministration. Administration of menatetrenone at a dose effective in improving osteoporosis may also be useful in restoring hematopoiesis in MDS patients, possibly by way of inducing differentiation.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Apoptosis; Calcifediol; Cell Differentiation; Drug Therapy, Combination; Female; Humans; Osteoporosis, Postmenopausal; Vitamin K; Vitamin K 2