LEUKAEMIA TREATED \>.\ RADIATION 



donor, it was obvious to niany tli.it here was a potential treatment for 

 leukaemia ol the mouse. 



This, like the analogous human condition, is a generalized disease involving 

 the normal haemopoietic and lymphopoietic tissues but infiltrating other 

 tissues as well. The characteristic leukaemia of the mouse is lymphoblastic 

 and the murine leukaemias with w hich we shall be concerned are of this 

 standard form. If the malignant lymphoid cells are as radio-sensitive as the 

 normal cells of the haemopoietic tissues, then in theory it should be possible 

 to destroy these malignant cells and replace them with a normal culture 

 from another animal. In point of fact, even Ijeforc the cellular repopulation 

 hypothesis had been substantiated, Hollcroft and her colleagues from the 

 National Cancer Institute at Bethesda** had tried this sort of treatment in 

 the case of a mouse lymphosarcoma and in generalized lymphomatosis of 

 the guinea-pig. Their results, however, had not been dramatic and their 

 report which appeared in a journal not widely read had escaped us. 



Our earliest results in attempting this form of treatment were also a 

 therapeutic failure, in that all the treated animals died. Nevertheless, there 

 was enough material to give us some encouragement. These results which 

 have been reported' can be summarized as follows: we had available to us 

 a radiation-induced lymphoblastic leukaemia (151/1) of the CBA strain of 

 mouse given to us by Dr. R. H. Mole. This was maintained by serial passage 

 of the leukaemic cells in CBA mice. The leukaemia in the early generations 

 of passage was strictly strain-specific. These mice of the CBA strain were 

 injected, either intravenously or intraperitoneally, wdth 10^ cells and a 

 period of seven days was allowed to elapse during which it w^as presumed 

 that the leukaemic cells would proliferate. In fact, it took about two to 

 three weeks, depending on the route of inoculation, for the mice to succumb 

 to the transmitted leukaemia. After seven days the injected mice were 

 irradiated at 43 rad/min with 950 rad of X-rays to the whole body. They 

 were then injected intravenously with normal bone marrow from adult 

 mice, or spleen from infant mice. 



In the first experiments, the normal cells injected came from mice of the 

 same inbred strain. This isologous material was adequate in reconstituting 

 the depopulated tissues, but after a lapse of about a month the mice died 

 with a recrudescence of the leukaemia. Therefore the dose of 950 rad given 

 at high dose rate had been insufficient to cause the complete elimination of 

 all the leukaemic cells. 



However, the other CBA mice, to which the leukaemia had been trans- 

 mitted in the same dose, were treated after irradiation, not with isologous 

 myeloid tissue, but with homologous material from mice of strains C57BL, 

 A or C3H. In some cases the homologous material came from normal mice, 

 in other cases from mice which had previously been immunized by two 

 injections of the CBA leukaemic cells. Some of these mice treated wdth 

 homologous material lived for several months and then died with a condition 

 of generalized wasting and loss of condition, a syndrome which is not un- 

 common when homologous or heterologous material has been administered. 

 It is often called 'secondary disease', because it is secondary in time; and it 

 is generally agreed that it is a consequence of an immunological reaction 

 between the elements of donor and host in the chimaerical animals. 



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