Variable Response of Bone Marrow to Feeding DL-5-Formyltetrahydrofolate in Pernicious Anaemia

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Abstract
The megaloblastic anemia in pernicious anemia may be due to inadequate intracellular concentration of monoglutamyl folates other than methyltetrahydrofolate caused by diminished conversion of methyltetrahydrofolate to tetrahydrofolate (methylfolate trap). To test this, the concentration of methyltetrahydrofolate was increased in the plasma of 6 patients with pernicious anemia by feeding DL-5-formyltetrahydrofolate. The effect of therapy on bone marrow morphology and routine hematologic parameters was measured. Of 2 patients receiving 800.mu.g/d of DL-5-fromyltetrahydrofolate, 1 had a singificant response; of 4 receiving 6 mg/d, 1 converted erythroid maturation to normoblastic, and in 2 others some improvement was noted in levels of neutrophils, platelets or reticulocytes although marrow morphology remained megaloblastic. Response did not correlate with the degree of elevation of plasma folate. In patients receiving this therapy, slight increase of methylcobalamin in plasma may have occurred (P < 0.05). These observations support ineffective utilization of methyltetrahydrofolate as the major cause of megaloblastic anemia in pernicious anemia, but indicate that the degree and location of block varied in different patients and in different precursor cells of a single patient.