The causes of the delayed coagulation of hemophilic blood seem to become clearer as time advances. On one side we have the investigations of the school of Minot, indicating a deficit in the globulin fraction; and on the other side are the works of those who maintain that there exists an excess of anticoagulant substances. We support the latter theory, although in our opinion the two theories do not contradict each other, since it might be possible that this anticoagulant substance would act on the globulin fraction diminishing its coagulant power. This substance could be identified with the anticephalin fraction of Tocantins. With the idea that this substance might be less stable than the coagulant fractions (fibrinogen, prothrombin, and thromboplastin) we have tried to render it inactive by keeping the blood in a refrigerator for a certain length of time. Inactivity was obtained in some of our experiments. We know that the stability of this substance varies from one patient to the other, but we have not been able to fix the cause of these variations. In conclusion, we consider that other means of neutralizing the action of this anticoagulant substance should be investigated. This inactivity once obtained, we should have advanced far in solving the intricate problem of hemophilia.

Summary: Through the use of DEAE‐cellulose under the conditions reported in this paper which were particularly selective for the adsorption of clotting factors, the chromatographic behaviour of Factors I, II, V, VII, VIII, IX and X was studied using different buffer systems. Human plasma, supernatant of Fraction I of Cohn and human Factor‐VIII concentrates were used as starting materials. As some of the chromatographic systems used do not perceptibly modify the physical and chemical properties of the plasma or its derivatives, they allow the techniques to be included in a general scheme of routine plasma fractionation. The conclusions drawn from the chromatographic behaviour of the factors studied have led to the preparation of a concentrate of Factors II, IX and X for clinical use, a concentrate of Factor VII and an artificial substrate for the assay of Factor VII.

One hundred ninety patients who had advanced active Hodgkin's disease, lymphosarcoma, or reticulum cell sarcoma were treated with a combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) given in a cyclical fashion every month. Complete remission was produced in 91 of 138 (66%) patients with Hodgkin's disease and in 39 of 52 (75%) patients with non-Hodgkin's lymphoma (lymphosarcoma and reticulum cell sarcoma). The response rate was higher in patients who completed six cycles of therapy compared to those who completed only three to five cycles: 77% vs. 45%, respectively, in Hodgkin's disease, and 85% vs. 46%, respectively, in non-Hodgkin's lymphoma. The median duration of remission was longer for Hodgkin's disease patients who completed six cycles (30 months vs. 10 months). The median duration of complete remission of non-Hodgkin's lymphoma was 14 months. The response to treatment correlated positively with survival. The median survival time start of COPP treatment for patients with Hodgkin's disease was 7 months for nonresponders, 14 months for those who attained partial remission, and more than 48 months for those who attained complete remission. For patients with non-Hodgkin's lymphoma, the median survival time from start of COPP treatment was 24 months for nonresponders and those who had partial remission, and more than 32 months for those who attained complete remission. Of complete remission responders with Hodgkin's disease, 70% are still alive 84 months after diagnosis, and 63% of the patients witn non-Hodgkin's lymphoma are still alive 48 months after diagnosis.

A total of 114 previously untreated patients with myeloblastic leukemia was included in a sequential therapy protocol. Daunorubicin, vincristine, and prednisone were employed for the first 3 weeks, followed by two or more 5‐day courses of cytosine arabinoside and 6‐mercaptopurine; there was a 5‐day rest between courses. Maintenance therapy was as follows: the continuing 6‐mercaptopurine and methotrexate treatment was interrupted every 30 days for sequential reinforcement courses consisting of one dose of daunorubicin and vincristine and 7 days of prednisone, or by a 5‐day course of cytosine arabinoside plus 6‐mercaptopurine. Of the 114 patients, 48 obtained complete remission, 14 had partial remission, 16 failed to respond, and 36 died during the course of treatment. The remission rate in children (under 16) was 57%; in adults (16–45) 54%; and in those over 45, 19%. The difference in the incidence of complete remission in patients under 45 and those over 45 was statistically significant (p < 0.01). The median duration of complete remission was 8 months: 12 months in children and 5 months in adults. The over‐all survival rate was 4 months: 13 months for patients with complete remission, 4 months for those with partial remission, and 1 month for patients who did not respond to therapy. The difference in survival of those with complete remission and all the others was significant (p < 0.01).

Phagocytosis and lysis of C. pseudotropicalis by peripheral blood monocytes from Hodgkin's and non-Hodgkin's lymphoma were analysed. In Hodgkin's disease, there was a decrease in the phagocytic activity of blood monocytes; moreover, the candidacidal activity was significantly decreased as compared with normal controls. Although monocytes from non-Hodgkin's patients presented normal phagocytic function, the ability to kill C. pseudotropicalis was impaired. In both groups of lymphomas, the data showed that the abnormal findings were not related to treatment. These results indicate that monocytes from Hodgkin's and non-Hodgkin's lymphoma posses a deficiency in killing C. pseudotropicalis, which could be due to an intrinsic macrophage defect in the myeloperoxidase-independent mechanisms and which may be responsible for the predisposition of the se patients to candida infections.

A total of 146 previously untreated acute lymphoblastic leukemia patients—126 children and 20 adults—has been studied prospectively in order to evaluate the relative efficacy and toxicity of: A) two induction of remission treatments (Group A: Daunorubicin‐vincristine‐prednisone vs. Group B: Adriamycin‐vincristine‐prednisone) and the use of the same drugs as reinforcement courses every 90 days during the 1st year of complete remission and every 180 days thereafter; B) the use of a short course of L‐asparaginase early in remission as intensification treatment (to half of Group A only (Group Aa); Groups Ab and B did not receive this treatment); and C) the use of 2400 rads cobalt‐60 irradiation to cranium coupled with five doses of intrathecal methotrexate as prophylactic CNS treatment. Complete remission was achieved in 85.7% of 112 cases of Group A and in 79.4% of 34 cases of Group B. The median duration of hematologic remission was 23, 21, and 22 months for Groups Aa, Ab, and B respectively. Toxicity was about the same for all regimens. The median duration of complete remission was 24 months, and of hematologic remission 27 months in the CNS prophylactically treated group, against 9 and 18 months, respectively, for the non‐treated group. We have concluded that: A) Adriamycin did not seem to be any better than Daunorubicin in inducing or prolonging complete remission when used in combination with vincristine and prednisone, either as induction treatment or in reinforcement courses; B) we did not demonstrate any significant difference in duration of remission, incidence, or site of relapse between L‐asparaginase‐treated and non‐treated patients; and C) the CNS prophylactic treatment employed in this trial is very effective in preventing CNS relapse, although it does not seem to prevent hematologic relapse.

A total of 227 patients—124 with acute lymphoblastic leukemia (ALL) and 103 with acute myeloblastic leukemia (AML)—have been studied in order to evaluate the therapeutic effectiveness of vincristine, daunorubicin, and prednisone for induction followed by consolidation courses every 6 months with these drugs and either 6‐mercaptopurine and methotrexate (plan A) or methotrexate alone (plan B) for maintenance of remission. In ALL, complete remission (CR) was achieved in 90.2% of untreated and 71.6% of previously treated patients. In AML, 34.8% untreated and 23.5% previously treated patients obtained CR. There was no statistically significant difference between the two maintenance regimens. Median duration of hematologic remission in ALL was 16 months and that of complete remission terminating in either meningeal, visceral, or bone marrow relapse was 9 months. Median survival was 18.2 months. In AML, the median survival was 11.8% months for those that achieved CR, 4.2 months for the partial remission (PR) group, and 0.9 months for nonresponders.

No abstract