The Plasma Disappearance of Radioactive Vitamin B 12 in Myeloproliferative Diseases and Other Blood

By CHARLES A. HALL With the technical assistance of Alexander E. Finkler, Edward S. Allen and Booker T. Moore T HE PLASMA vitamin B12 is abnormally high in chronic myelocytic leukemia.’8 It is sometimes increased above normal in polycythemia vera35 and myeloid metaplasia,35 but usually not as strikingly so. The plasma vitamin B12 is normal in chronic lymphocytic leukemia,12’4’5’8 lymphoma,4’5’8 myeloma,3’4 and acute lymphoblastic leukemia.1’6 It is usually normal in undifferentiated acute leukemia,2’5 but high levels have been reported.4 Many patients with acute or subacute myeloblastic leukemia have a normal plasma B12, but in some cases it is markedly elevated.3’6’8 It may be elevated in DiGuglielmo’s syndrome.9 This abnormality of plasma vitamin B12 appears to be found in the diseases often grouped as myeloproliferative disorders, but not in other neoplasms of the blood forming organs. Not only is the plasma B12 high in chronic myelocytic leukemia, but the capacity of plasma to bind added vitamin B12 is increased.2’57 This high binding capacity probably Is due to an increase in the normal B12 binding protein.10’ The exact nature of this protein is unknown, but it is in the seromucoid fraction of plasma protein.10’ Four groups12 5 have further studied the problem by determining the rate of plasma disappearance of a small intravenous dose of radioactive vitamin B12. Although the dose ranged from 0.5 to 4.0 ttg., all four groups demon. strated a distinct slowing of the disappearance of the B12 from the plasma in chronic myelocytic leukemia. Miller et al.13 also found some slowing of disappearance in two patients with myeloid metaplasia, while a patient with chronic lymphocytic leukemia had a normal disappearance curve. Weinstein and Watkin16 found slowing of plasma disappearance in chronic myelocytic leukemia and myeloid metaplasia after 0.5 ttg. oral doses of radioactive B12. The present study was designed to determine whether the abnormality of plasma disappearance was common to all disorders of the myeloproliferative group, and whether it occurred in other blood diseases where there is hyperplasia or neoplasia of a particular cell series. In order to keep the intravenous dose as close to a tracer dose as possible, the usual dose was 0.040.05 tg. The normal total plasma B12 in this laboratory is of the order of 400 , tg./ml. and thus this test dose would be about 3.5 per cent of the total plasma content of a subject with a plasma volume of 2700 ml. Using the minimum value for total B12 binding capacity of 650 1 tg./ml., a normal subject could completely bind the test dose in approximately 160 ml. of plasma.