Variable response of bone marrow to feeding DL-5-formyltetrahydrofolate in pernicious anaemia.

It has been suggested that the megaloblastic anaemia in pernicious anaemia is due to inadequate intracellular concentration of monoglutamyl folates other than methyltetrahydrofolate caused by diminished conversion of methyltetrahydrofolate to tetrahydrofolate (methylfolate trap). To test this, we have increased the concentration of methyltetrahydrofolate in the plasma of six patients with pernicious anaemia by feeding DL-5-formyltetrahydrofolate. The effect of therapy on bone marrow morphology and routine haematologic parameters was measured. Of two patients receiving 800 mug/d of DL-5-formyltetrahydrofolate, one had a significant response; of four receiving 6 mg/d, one converted erythroid maturation to normoblastic, and in two 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 less than 0.05). These observations support ineffective utilization of methyltetrahydrofolate as the major cause of megaloblastic anaemia in pernicious anaemia, but indicate that the degree and location of block varied in different patients, and in different precursor cells of a single patient.