G. Watson James

A Simple Direct Method for Absolute Basophil Leucocyte Count.

Summary A method is presented which permits the differentiation and enumeration of basophils from the counting chamber. Basophil counts were performed on 69 normal individuals and the range, mean, and standard deviation are reported by sex.

Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113.

Abstract One hundred and forty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with protocol defined combination chemotherapy-radiotherapy by 25 member institutions of the Cancer and Leukemia Group B. Induction of remission was attempted with vincristine (V), prednisone (P), L-asparaginase (A), with or without intrathecal methotrexate (IT-MTX) and followed by daunorubicin (D) in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 72%; daunorubicin was needed to achieve CR in 20 of the 107 remitting patients. The administration of IT-MTX during remission induction, especially when given simultaneously with A, was found to increase toxicity without therapeutic benefit. Remissions were maintained with either parenteral courses of 6-mercaptopurine (6-MP), and methotrexate (MTX), plus intermittent doses of V, P, and bis-β-chloroethylnitrosourea(BCNU) or with daily oral 6-MP, weekly oral MTX, and periodic VP reinforcements. All patients remaining in remission for 3 months or longer received CNS chemoradiotherapy. Median remission duration was 15 months. Continuous oral maintenance proved at least equivalent to intermittent parenteral remission therapy. Median survival was 17 months for all patients and 29 months for qualified patients achieving CR. Frequency and duration of response, and duration of survival were independent of age between ages 30 and 60. Above age 60 the prognosis is significantly less good. Thirty-two percent of the responders (life table estimate) remain in continuous first remission at 5 y. Toxicity was acceptable, except for an excessive frequency and severity of infections: (1) when V, P. A, and IT-MTX were given simultaneously; and (2) early in remission when full doses of maintenance chemotherapy were employed prior to complete recovery of normal bone marrow function. Results of treatment of ALL in adults have improved markedly during the last decade but lag behind those observed in children for reasons as yet unexplained.

A comparative study of a bcnu containing 4-drug program versus mopp versus 3-drug combinations in advanced Hodgkin's disease. A cooperative study by the cancer and leukemia group B

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkins disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3‐drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4‐drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3‐drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4‐drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

The Heart in Anemia

The following brief summary seems justified from the large volume of accumulated data dealing with the reaction of the cardiovascular system in the anemic patient. There are four mechanisms operating in the anemic patient which may increase the supply of oxygen to the tissues when the oxygen carrying capacity of the blood is reduced. Under conditions of rest, a rapid velocity flow and tachycardia with an increase in minute volume of cardiac output is the first response to anemia. As compensation develops, tachycardia and increased velocity flow are largely replaced by selective shunting of blood and the removal of an increasing percentage of oxygen in the tissue capillaries from each gram of circulating hemoglobin. These later physiologic mechanisms are best illustrated by patients with chronic parasitic anemias. Under conditions of physical stress each of the four physiologic mechanisms contribute in meeting the demands for increased oxygen requirements. Compensation is, however, never perfect; the status of the patient is determined by the reduction in hemoglobin, the tissue oxygen requirements, the presence of physical changes in the cardiovascular and pulmonary systems, degree of oxygen abstraction from the blood, and the selective shunting of blood. In relatively acute anemia, dyspnea readily occurs on physical exercise. Reduction in the ventilatory capacity of the lung occurring in some anemic patients results from an over-all reduction in physical fitness due to the anemic state rather than to physical changes in the lung. In well compensated, chronic anemia, the vital capacity of the lungs is frequently above normal and similar to that observed in athletes and completely acclimatized, high altitude inhabitants. In the absence of cardiovascular disease or physical or metabolic factors requiring increased cardiac output, true congestive heart failure rarely results from the anemic state. Effort angina is uncommon in anemic patients and when present is usually related to underlying coronary artery disease. Cardiac hypertrophy under certain conditions results from prolonged anemia. Since cardiac hypertrophy is rightly placed in the category of organic heart disease, one is justified in classifying chronic anemia as one of the etiologic factors in the production of heart disease.

Effectiveness of Thiocyanate Analog of Vitamin B12 in Pernicious Anemia.

Summary The thiocyanate analog of vit. B12 (thiocyanato—cobalamin) has been shown to be fully active hematologically in pernicious anemia. In two patients the early biochemical and hematologic responses were the same as observed with same dosages of vit. B12. Further evaluation of the neurological response to this analog is necessary.