The results of 9 years’ experience with acute stem cell (lymphoblastic) leukemia treated with a combination of steroids and antimetabolites, designated as "composite cyclic therapy" (CCT), are described and their theoretical implications are discussed. In 175 patients surviving at least one month after diagnosis the per cent survivals were: 17.2 months (50 per cent), 27.5 months (25 per cent), and 45.0 months (10 per cent). Six patients were alive in uninterrupted remission at the close of the study, from 4-9 years after diagnosis. The mean survival of the expired patients was 17.7 months, with a median of 14.5 months. The mean duration of the first remission was 15.2 months with a median of 12.5.

The therapeutic response in terms of remission rate and total survival was significantly better in stem cell leukemia, as defined cytologically at the time of original diagnosis, than in other types, suggesting that the effect of steroids on the former is at least in part specific for malignant cells of lymphoid origin.

A highly significant difference within the group of stem cell leukemia was observed between patients with initially low as compared to high white blood count, the dividing line being at 20,000 cells/mm.,3 the latter having twice the mean survival of the former. Of the 44 patients achieving survival of 2 years or more only one had an initial white count of more than 20,000. In conjunction with chromosome studies published elsewhere these findings suggest that the initial white count is a parameter, possibly of immunologic nature, indicative of the partial retention or complete loss of control over leukemic mutant cells. The possibility is discussed, on the basis of theoretical considerations and the observed role of long first remissions in the total survival time, that conditions and measures taken in the early stages of therapy may be decisive for the ultimate course. The current evidence for the mutational nature of acute leukemia permits the theoretical distinction between remission as the temporary suppression of a mutant stem line as opposed to a "cure" representing its permanent elimination, and to explain occasional apparent cures, including some observed in the present series, on that basis.

Clinically, combined cyclic therapy or CCT appears to be superior to the use of single antimetabolites. The withholding of steroids until these drugs become ineffective does not at present appear justified.

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