J. F. LOUTIT 



Congdon^ and Makinodan^, from Oak Ridge, have in the past expressed 

 their opinion that this 'secondary disease' is caused by the host recovering 

 its immunological capacity and reacting against the graft. However, our 

 published views^*' on the other hand are that it is due to the donor material 

 maturing as lymphoid tissue and setting up an immunological reaction 

 against the host's antigens. The fact that some of these 'leukaemic' CBA 

 mice, recolonized with foreign homologous bone marrow, did in fact not die 

 of the recurrence of their leukaemia but of 'secondary disease' is, we think, 

 one of the pieces of evidence which favours our hypothesis and we have 

 further evidence from a number of different angles^^ 



For the moment we accept that the donor tissue does react against the 

 host on normal tissue and malignant alike. It may be possible ultimately 

 to use this reaction in therapy, but the approach will have to be more refined 

 than in our original exercise, and certainly, even today, we are unable to 

 use the reaction against the unwanted malignant cells with the fine control 

 that would be necessary. 



Whatever may be the possibilities arising from the use of homologous 

 material after lethal doses of radiation, our next approach was to see if we 

 could get a more efficient extinction of the leukaemic cells by means of the 

 radiation alone, followed, of course, by injections of isologous myeloid 

 tissue. It happened that in the laboratory, at the same time, other mice 

 were being irradiated continuously over 25 hours. As one would predict the 

 dose-response relationships for this irradiation at low intensity were different 

 from those at the higher intensity: 1450 rad, given in the 25 hours, was the 

 LDgg corresponding to the 950 rad given in 20 minutes or so. 



Therefore, CBA mice, to which the leukaemia had been transmitted 

 seven days earlier, were introduced into this experiment and given a dose 

 of 1620 rad in 25 hours. The original leukaemia 151/1 was used for the first 

 of several experiments; it was then in its fifth to seventh generation of 

 passage. For the irradiation, the mice were placed in groups of five, in 

 aluminium cages having a floor area of 25 x 10 cm^ and a height of 12 cm. 

 Food and water were available throughout the irradiation. The Siemens 

 Stabilipan X-ray-therapy set was operated at 250 kV constant potential and 

 at 4 or 6 mA, the half- value layer being 1 • 2 mm copper. The beam was 

 directed horizontally through the sides of the cages and the distance of the 

 tube was such that the movement of mice within their cages would not alter 

 their dose by more than a few per cent. 



After the mice were removed from the radiation field, they were injected 

 with normal isologous CBA bone marrow. The preliminary results of the 

 first three runs have already been reported ^^ and are shown in Table 1. In 

 these experiments some of the mice had originally been injected with 

 leukaemic cells subcutaneously; three months after the therapy 17 out of 20 

 were still alive. Five mice had received the leukaemic cells intravenously 

 and three out of these five were also alive. 



The later results and further experiments using this array were presented 

 this year at the Third Canadian Cancer Conference and will be reported in 

 due course in the volume of the Proceedings. The following data are therefore 

 a recapitulation of this report^^. 



Firstly, several additional leukaemias have been included in the series. 



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