Total body irradiation for myelomatosis.

In the first myeloma trial of the M.R.C. working party on leukaemia in adults the deaths that have occurred can be attributed to unrelated diseases (5%h-for example, cosonary thrombosis, etc.); causes indirectly telated to the tumour (80,for example, pneumonia due to the immune paresis); no obvious response of the tumour to treatment (27/); and finally relapse of the tumour after an initial response to treatment (600%). In analysing this last group it became clear that in nearly half of these patients the relapsing tumour was more aggressive than it had been initially. This occurred more often in those patients whose paraprotein levels fell rapidl) (to under half the initial level within three months) than in those where a slower response to cytotoxic drugs was observed. The rapid responders also showed initially lower levels of serum albumin, perhaps reflecting their faster initial growth rates and protein production. A fast response could be due to a loss of the normal resting phase (memory cells) of antibody-forming cells, and where this is apparently retained in the slow responders a better prognosis is assured. During the relapse four types of "escape" could be distinguished. Firstly, 450' of the 600o showed a change to a faster growth rate (growth rate escape). This group included the other types of escape-secondly, 350/ showing the appearance de novo or an increased proportion of Bence Jones production (Bence Jones escape); thirdly, 5°/ , a clear change in the paraprotein pattern (mutation escape); and, fourthly, 3%, loss of paraprotein production reveiting to a "reticulosarcoma" (non-paraprotein escape). These changes (like the induction of monocytic leukaemia) mostly require 18 months or longer to appear, a period compatible with a mutagenic action of the cytotoxic drugs. Longcontinued cytotoxic treatment should therefore be reserved only for patients (especially so in childhood) who would otherwise die of their disease.