The Threshold Dose of P³² for Leukemic Cells of the Lymphocytic and Granulocytic Series

Analyses of the threshold dose of P³² to control 201 chronic lymphocytic leukemia patients and 100 chronic granulocytic leukemia patients and of the P³² dose to maintain 133 chronic lymphocytic leukemia patients for a mean period of 50.2 months and 49 chronic granulocytic leukemia patients for a mean period of 33.6 months are analyzed. These threshold doses fit the logarithmic probability distributions given in the tables and figures.

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When the dose in mc. to control was plotted against the leukocyte count, a straight line was obtained on log log paper. The equation for this curve for the median dose to control chronic granulocytic leukemia is: log mc. P³² per 12 weeks = 0.33 log L - 0.633, where L is the leukocyte count on the day the first P³² was given. The equation for the log log curve relating median dose to control chronic lymphocytic leukemia to initial counts above 15,000 is: log mc. P³² per 12 weeks = 0.47 log L - 1.420. But the 40 aleukemic or subleukemic cases with leukocyte counts below 15,000 had a median P³² requirement and standard deviation that did not differ significantly from that for the entire group, suggesting that this subleukemic group includes patients resembling the entire spectrum of cases with elevated initial leukocyte counts.

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The median dose of P³² per year to maintain chronic granulocytic leukemia cases fits the equation: log P³² per year = 0.546 log L - 1.506, and the corresponding equation for chronic leukemic lymphocytic leukemia is: log mc. P³² per year = 0.45 log L - 1.22. The group of lymphocytic leukemias with initial counts below 15,000 again showed a median and distribution similar to that for the entire leukemic group.

The remarkable fact that the dose requirement years later is related to the initial leukocyte count is discussed. Revised recommendations on dosage schedule for titrated, regularly spaced P³² therapy of the chronic leukemias are presented.

For each individual patient with chronic leukemia, there is a threshold dose of intravenously administered P³² below which no effect is observed. The dose and interval which will maintain a uniform leukocyte count of about 15,000 may remain unchanged for years or may show abrupt changes at any time to either a lower or higher requirement.