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Three-hundred and ninety-nine patients with acute leukemia examined during the period 1947-1964 were divided into three sequential series and their survival, from diagnosis to death, was compared. A statistically significant increase in duration of survival for myeloblastic leukemia from a median of 2 to 5 months occurred between series I and series III. This is the first convincing evidence that 6-mercaptopurine therapy influences survival in myeloblastic leukemia. A steady increase in median survival of patients with lymphoblastic leukemia from 4 to 8 to 12 months was found in the three series. The results of analysis of these series are compared to other reported series. The hypothesis —that the longer survivals reported for patients treated in hematology clinics compared to that of patients selected from population areas reflects patient selection—was examined and appeared unlikely.

The longevity, reckoned from the symptomatic onset of acute leukemia as well as from the initiation of treatment, of a group of 89 cases including children and adults, treated in this clinic since March, 1954, was found to exceed that of a similar group of 78 patients treated in preceding years in the same clinic. The median survival of all cases considered as a unit was increased from three to six months, as measured from the date treatment was begun. The change was found to be statistically significant as well as clinically important. The longer survival found in the 1954-57 series correlated with the greater use of three, rather than only two, chemotherapeutic agents. On analysis, improved survival was statistically proven only for individuals with lymphoblastic leukemia; for these, the median survival was 10 months after the symptomatic onset of leukemia and 7½ months after the start of treatment. Within this group, there was an even greater improvement for those whose leukocyte values immediately prior to the initiation of therapy were less than 10,000 per cu.mm.; half of these patients lived more than 12 months after treatment was begun. The reason for the exceptional longevity of patients with the lower pre-treatment leukocyte values is unknown. It appears that one can attribute at least part of the improvement to therapy. The type of statistical analysis used presents the minimum figures for improvement in median survival. When the ultimate longevity is known for the 17 per cent of the cases surviving at the closing date of the study an additional small increment may be found. The relative inefficacy of chemotherapy in myeloblastic leukemia should be a signal for greater screening of new agents in this type of tumor.

A case with a prolonged period of blood disorder preceding the terminal development of myeloblastic leukemia is reported in some detail. The preleukemic period was characterized by anemia, neutropenia and thrombocytopenia. It extended over a period of almost nine years but was punctuated by a period of remission lasting four and one half years. In the initial phase, the marrow was hypoplastic but during the later stages, it was hyperplastic. Brief reference is made to somewhat similar cases that have been recorded and to the ideas expressed by the authors of these reports. It is suggested that further investigation is needed to determine whether the initial blood disease occurring in such cases is irrevocably linked to the subsequent leukemia.

Four cases of severe refractory anemia with an enormous increase of demonstrable free iron in the normoblasts are reported. Three cases were of unknown etiology and of benign course but in the fourth the anemia was probably related to rheumatoid arthritis or to the onset of myeloblastic leukemia. The significance of the sideroblastic bone marrow in these cases is discussed and the opinion expressed in the literature—that it indicates a defect in hemoglobin synthesis is subscribed to. Thus, it is believed that the anemia in these cases is due to degenerative changes in the bone marrow which also have some morphologic manifestations. The disturbance of marrow activity is probably best reflected in the reticulocyte counts.

A detailed study (phase contrast, bright field and electron microscopy) of the primitive leukemic cells from a patient with atypical myeloblastic leukemia has been presented. An unusual mucopolysaccharide-containing vacuole has been observed and characterized both morphologically and histochemically. In addition, this study has yielded considerable information concerning the structure and chemical composition of the fibrillar formations, fat droplets and the alterations in erythrocytes following their ingestion by the leukemic cells. Intramitochondrial structural alterations have been observed and characterized in many of the primitive myeloblasts. Changes in the mitochondria and endoplasmic reticulum may reflect impaired or altered metabolism in these abnormal leukemic cells.