Polycythemia Vera: Age Relationships and Survival

Study of our first 201 cases of polycythemia vera and of cases reported inthe literature shows a remarkable age distribution for this disease. The ageat onset, age at diagnosis, age at first treatment, and age at death, as well assurvival times, each fits a normal distribution.

In our cases, the median age at onset is 57 years with a standard deviationof 13 years, an entirely different distribution from that for the populationof Oregon. This requires a logarithmic increase in relative age specific incidence from age 20 to 40, when there is little difference in the number ofpersons alive at each age, with a doubling of the proportion occurring ineach 5-year interval every 7.5 years. After age 55, the proportion of newcases developing follows the slope of the number alive in the population.This means that the incidence remains almost constant after the peak ageincidence is reached.

Unfortunately, no data exist to transform these figures to absolute values,but if enough of the population could be studied to give absolute values atany one point, all other points could be determined. The implication is thatpolycythemia vera is due to a single cause which is highly correlated withage.

The normal distribution of survival times means that polycythemia verais not a malignant process since survival times in all malignancies studiedfit a log normal distribution. The constant value of age at death means thatage at first treatment is a most important prognostic factor.

The mean age at death of patients with polycythemia vera, treated withP³², is 69 years ± 1, and treated without radiation therapy is 65 years ± 1.Apparently, if a patient lives to be treated with P³² previous treatment byother modalities or no treatment prior to that, will not affect the years tobe gained by P³² treatment. However, the total survival time is highly correlated with age and the sooner after onset that the patient can be treatedthe more likely it is he will benefit from P³² therapy.

     

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 lymphocyticleukemia patients and 100 chronic granulocytic leukemia patients and of theP³² dose to maintain 133 chronic lymphocytic leukemia patients for a meanperiod of 50.2 months and 49 chronic granulocytic leukemia patients for amean period of 33.6 months are analyzed. These threshold doses fit the logarithmic probability distributions given in the tables and figures.

See PDF for Figure

See PDF for Figure

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 curvefor the median dose to control chronic granulocytic leukemia is: log mc. P³²per 12 weeks = 0.33 log L - 0.633, where L is the leukocyte count on theday the first P³² was given. The equation for the log log curve relating mediandose to control chronic lymphocytic leukemia to initial counts above 15,000is: log mc. P³² per 12 weeks = 0.47 log L - 1.420. But the 40 aleukemic orsubleukemic cases with leukocyte counts below 15,000 had a median P³² requirement and standard deviation that did not differ significantly from thatfor the entire group, suggesting that this subleukemic group includes patientsresembling the entire spectrum of cases with elevated initial leukocyte counts.

See PDF for Figure

See PDF for Figure

The median dose of P³² per year to maintain chronic granulocytic leukemiacases 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 withinitial counts below 15,000 again showed a median and distribution similar tothat for the entire leukemic group.

The remarkable fact that the dose requirement years later is related to theinitial leukocyte count is discussed. Revised recommendations on dosageschedule for titrated, regularly spaced P³² therapy of the chronic leukemiasare presented.

For each individual patient with chronic leukemia, there is a thresholddose of intravenously administered P³² below which no effect is observed. Thedose and interval which will maintain a uniform leukocyte count of about15,000 may remain unchanged for years or may show abrupt changes at anytime to either a lower or higher requirement.

Submitted on November 6, 1959 Accepted on January 4, 1960     

A method for the rapid separation of leukocytes and nucleated erythrocytes from blood of marrow with a phytohemagglutinin from red beans (Phaseolus vulgaris)

A method is described for rapid and efficient separation of leukocytes and nucleated erythrocytes from blood or marrow. It is based on the rediscovery of a nontoxic hemagglutinin, isolated from common red or navy beans, which agglutinatesall human erythrocytes and those of the animals which have been tested with it.The time from drawing the blood to complete separation of the cells is less thanten minutes. The cells remain in suspension in their own plasma and are countable.Negligible amounts of foreign material are introduced, a great advantage in chemical studies. The cells so isolated are living and suitable for culture studies. Anyvolume of blood from less than 1 ml. to over 500 ml. may be processed. In marrownucleated erythrocytes are separated with the leukocytes and in their originalporportions. The volume, motility, morphology and life span of the cells in cultures are not altered by addition of the bean extract.

     

Continuous tissue culture of leukocytes from human leukemic bloods by application of gradient principles

Two methods of tissue culture based on gradient principles which have permitted continuous growth and multiplication of hemic cells for 6 months to 1year are described. Three long-term cell strains were isolated from the bloods ofpatients with acute or chronic leukemias. Success with these methods dependson previous determination of the gradient factor for the particular cell type tobe cultured. This can easily be accomplished by the gradient culture method,and these principles are in all probability applicable to all cell types grown intissue culture.

The isolation of these cells from blood excludes a fixed tissue cell as the onlytype capable of long term multiplication. The development of cells resemblingtissue histiocytes, Dorothy Reed cells, and Langhan’s giant cells from cells cultured from the blood of acute monocytic leukemia lends further support to theview that the monocytic series and the histiocytic series (reticuloendothelialcells) are one and the same and can give rise by polyploidy and endomitosis tomany types of giant cells.

Submitted on April 6, 1955 Accepted on July 11, 1955