JOHN H. LAWRENCE, M.D., D.SC., F.A.C.P.; H. S. WINCHELL, M.D., PH.D., F.A.C.P.; W. G. DONALD, M.D., F.A.C.P.
Since the initial use of 32PO4 in our clinic in 1939 for the treatment of polycythemia vera we have followed to termination 181 cases of the disease treated with 32P or 32P and X ray. Of these patients 45 of 181 (25%) developed significant splenic myeloid metaplasia, and 26 of 181 (14%) developed an acute myelogenous leukemia-like state. Sixteen patients had both "acute leukemia" and significant splenic myelopoiesis or myeloid metaplasia (that is, 16 of 45 or 36% of all cases with myeloid metaplasia developed "acute leukemia"), and 10 patients had only "acute leukemia" but no significant splenic myeloid metaplasia (that is, 10 out of 136 or 7% of all patients without myeloid metaplasia developed acute leukemia).
Patients who failed to develop myeloid metaplasia or acute leukemia, or both, were older at the time of onset and diagnosis than those with these developments and did not survive as long. The survival of patients who developed acute leukemia was not significantly different from patients who died with significant myeloid metaplasia alone.
The largest values of overall radiation exposure (both 32P and X ray) times time at risk were received by patients dying with splenic myeloid metaplasia alone.
The overall incidence of acute leukemia in this series of patients with polycythemia vera is 20 to 40 times greater than that expected for a population of "normal human subjects" exposed to similar radiation doses and times at risk.
These data are consistent with the hypotheses  that development of significant splenic myeloid metaplasia and acute leukemia-like states are part of the evolutionary history of polycythemia vera;  that myeloid metaplasia usually precedes the appearance of acute leukemia; and  that the incidence of acute leukemia in our patients treated with 32P may be primarily a result of prolonged survival rather than radiation dose.
LAWRENCE JH, WINCHELL HS, DONALD WG. Leukemia in Polycythemia Vera: Relationship to Splenic Myeloid Metaplasia and Therapeutic Radiation Dose. Ann Intern Med. ;70:763–771. doi: 10.7326/0003-4819-70-4-763
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Published: Ann Intern Med. 1969;70(4):763-771.
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