James L. Tullis

New multiple-agent chemotherapy (B-DOPA) for advanced Hodgkin's disease

B‐DOPA (Bleomycin (B), D‐imidazole carboxamide (D), Oncovin (O), Prednisone (P), Adriamycin (A) is a program developed for the treatment of Hodgkins disease resistant to MOPP therapy. Twenty unselected patients were treated by the following dose schedule: B, 4 mg/m2 days 2 and 5; D, 150 mg/m2 days 1 to 5; O (vincristine), 1.5 mg/m2 days 1 and 5; P, 40 mg/m2 days 1 to 6; A, 60 mg/m2 day 1. Each course, was repeated at 3 to 4 week intervals to maximum adriamycin dose of 450 mg/m2. All patients had received prior MOPP therapy and six had received prior radiotherapy. Fifteen of the 20 patients entered into the study were evaluable for response. There were nine (60%) complete responders and three (20%) partial responders. The median duration of complete remission was 14+ months with six of nine patients remaining in remission to a maximum of 21 months. The median survival of the nonresponders was 3 months. B‐DOPA is an effective combination chemotherapy regimen for advanced Hodgkins disease in patients who have previously received MOPP treatment, including patients who are refractory to MOPP therapy. The B‐DOPA program, or modifications thereof, may be integrated into primary treatment programs for advanced Hodgkins disease.

PHAGOCYTOSIS‐PROMOTING FACTOR OF PLASMA AND SERUM

In the earlier part of this monograph there have been presented scholarly delineations of the various proteins, nutritional factors, hereditary factors, and possible biochemical factors that comprise the natural viricidal and bactericidal property of tissues and body fluids. I should like now to direct your attention to another line of defense in the maintenance of homeostasis: leukocytic phagocytosis, as mentioned by J. G. Hirsch elsewhere in this publication. This system requires the simultaneous presence of 3 component parts: the bacteria or particle to be ingested, living migratory cells to do the ingesting and, finally, extracellular protein factors capable of converting the phenomenon from an interesting laboratory demonstration to a rapidly consummated biologic phenomenon exerting significant effect upon host survival. During the past 4 years our laboratory has been engaged in attempts to isolate and identify the proteins of plasma and serum responsible for this acceleration of phagocytosis. The presence of such phagocytosis-stimulating substances is not a new finding. In fact, the literature in this field dates back more than a half century. Unfortunately, however, this literature sometimes has been enmeshed in semantics: Should such factors be called opsonins? Should such factors be called alexin? Or, indeed, are such factors merely manifestations of complement activity? For purposes of simplification we have grouped all the protein factors that stimulate natural nonimmune phagocytosis under the descriptive term, phagocytosis-promotion factors or PPF. These factors will so be referred to in this report. Points a t which such activity varies from the classic concepts of complement and opsonins will be amplified. It should be noted that these protein factors are additive to the intrinsic ability of leukocytes to be ameboid and to ingest particles a t a slow but measurable rate in even a protein-free medium. These PPF factors also are separate and distinct, we believe, from the specific phagocytic stimulation that occurs in a sensitized system of immune antibodies and appropriate bacterial strains. Finally, the PPF factors also may be independent of alterations in phagocytic rate that can be mediated through metabolic or hormonal influences acting upon the intracellular kinetics of the leukocyte. What, then, are the PPF factors? We believe them to be the proteins that are concerned with the natural regulation of phagocytic rates within the intact animal. In this regard i t should be noted that Y. Matoth, of the Hebrew Medical School, Jerusalem, Israel, while working with us a few years ago, demonstrated the presence of these stimulatory factors in the fetal-cord serum of newborn infants. Admittedly the phagocytic enhancement of these factors was less than that of the whole plasma or serum of the maternal circulation when added to a suspension of the same fetal leukocytes. Nevertheless, welldefined phagocytic stimulation was demonstrable under neonatal circumstances.

clinical experience with auto and homo transplants of blood frozen up to five years

INCE 1956 the long-term preservation S of blood has been studied a t the U.S. Naval Hospital, Chelsea, Massachusetts, in cooperation with the Protein Foundation of Boston, Massachusetts. Preliminary reports1 have been satisfactory, and this process is now in active clinical operation on a daily basis. This technic eliminates many of the disadvantages and hazards inherent in the use of ACDpreserved blood, and will inevitably affect the clinical practice of many anesthesiologists during the next few years. For example, criteria for blood replacement will change when the blood to be transfused is the patients own, banked and frozen some months or even years prior to operation.

On the Nature of Leukotoxic Factors in Serum

was in contrast to the drug-induced leukopenias (aminopyrine, nitrogen mustard, chlorambucil, and X-ray) which were characterized by marrow aplasia wherein positive leukocyte antibody tests were never found. Preparation of R-3, RP, and properdin from positive (leukocyte antibody-containing) sera according t o the method of Pillemer showed that most of the positive activity is present in the R-3 fraction. I n the fractionated state, the anti-leukocyte activity becomes thermo-labile, as opposed to its thermo-stability in whole serum. At the suggestion of Dr. Andre Eypuem, RP and properdin made from normal serum were tested and found to be anti-complementary when used in the standard test system. R-3 can be substituted for “complement” in the standard test system. Heating RP and properdin to 56” eliminates the anti-complementary activity.