Higby Dj

Diaminodichloroplatinum: A phase I study showing responses in testicular and other tumors

Diaminodichloroplatinum was studied in a Phase I trial. Two dose schedules were explored. In Schedule I, a maximum dose of 100 mg/M2 given once was reached, and this proved too toxic for further use. The maximum dose in Schedule II, 24 mg/M2 daily for 5 days, was also too toxic, so 20 mg/M2 per day for 5 days was the dose selected for further exploration. Responses were seen in 1 patient with anaplastic thyroid carcinoma, 1 with transitional cell carcinoma of the bladder, and 1 with breast cancer. In patients with testicular tumors, responses were seen in 9 of 11 patients. There were 3 complete regressions seen, 1 in seminoma, 1 in embryonal cell carcinoma, and 1 in male choriocarcinoma. Three partial regressions, and three cases of objective improvement were also seen in this series. These were also distributed over different tumor types. The possibility that diaminodichloroplatinum has a specific effect on tissues arising from the genitourinary anlage is suggested.

Filtration leukapheresis for granulocyte transfusion therapy. Clinical and laboratory studies.

To study the clinical efficacy of granulocytes obtained by filtration leukapheresis, patients with clinically evident infection and granulocyte counts of smaller than 500 per cubic millimeter were randomly assigned to receive conventional therapy alone or with a granulocyte transfusion obtained from a single donor each day for four days. Five of 19 control patients survived to day 20, and 15 of 17 in the transfused group survived. Comparison of the two populations for variables such as age, disease, and severity and type of infection revealed no other factor that could account for the difference in survival. Outcome was not demonstrated to be related to HL-A match, post-transfusion counts, or presence of leukocyte antibodies. Functional studies of granulocytes obtained by filtration leukapheresis showed only minor differences although appearance was altered. Granulocytes so obtained can be used safely and efficaciously as adjunctive therapy for infection associated with granulocytopenia.

The Prophylactic Treatment of Thrombocytopenic Leukemic Patients with Platelets: a Double Blind Study

Eighteen patients with thrombocytopenia and acute leukemia were randomized in a double blind study to receive either platelets or platelet‐poor plasma as prophylaxis against bleeding. Despite no significant differences in platelet counts between patients of the two groups, the frequency of bleeding in the two groups was significantly different, affirming the value of prophylactic platelet transfusions. Fever preceded substantial hemorrhage in 10 of 13 patients, suggesting that infection may initiate bleeding in thrombocytopenic patients.

Graft-versus-host reaction following blood product transfusion☆

The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkins disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkins disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p less than 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p less than 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10(7)/kg. Adults seem more resistant to homografts than do children, and the hosts cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.

An Outbreak of Invasive Aspergillosis Among Allogeneic Bone Marrow Transplants: A Case-Control Study

Between April 1982 and March 1983, 10 of 26 (38.4%) allogeneic bone marrow transplant recipients housed on a newly opened bone marrow transplant unit developed invasive aspergillosis. By contrast, between September 1977 and March 1982, only 3 of 46 (6%) transplant recipients developed invasive aspergillosis. A case-control study to identify host factors related to Aspergillus infection found that aspergillosis was more common in patients with chronic myelogenous leukemia and aplastic anemia, older patients, patients having cytomegalovirus disease, patients who experienced prolonged granulocytopenia, patients conditioned with ara-C (100-200 mg/day), and patients who received longer duration of antimicrobial therapy. A series of logistic regression analyses revealed that underlying disease was the single best predictor of Aspergillus infection. This study demonstrates that underlying disease is an important risk factor for aspergillosis and that special measures may be warranted when transplanting certain patients.

Improving the care of patients with regard to chemotherapy-induced nausea and emesis: the effect of feedback to clinicians on adherence to antiemetic prescribing guidelines.

PURPOSE To evaluate the effect of performance and outcomes feedback on adherence to clinical practice guidelines regarding chemotherapy-induced nausea and emesis (CINE). METHODS Institutional CINE clinical practice guidelines were developed based on American Society of Clinical Oncology guidelines. Consecutive administrations of moderately/highly emetogenic chemotherapy were assessed for errors. Baseline statistical process control (SPC) charts were created and mean errors per administration were calculated. Prospective SPC charts were used to measure the effect of guideline development and distribution, a visiting lecturer, and ongoing feedback regarding compliance with guidelines employing SPC charts. Patients were surveyed regarding the extent and severity of CINE for 5 days postadministration. These outcomes were then shared with physicians. RESULTS Baseline compliance was poor (mean, 0.87 omissions per chemotherapy administration), largely because of inadequate adherence to recommendations for delayed CINE management. Most patients experienced delayed nausea, particularly on day 3 postchemotherapy. Physician prescribing performance did not undergo sustained improvement despite guideline development or distribution, a lecture by a visiting expert, or sharing of adherence data with clinicians. Once patient outcomes were shared, physicians accepted the need for compliance and instituted nurse practitioner antiemetic prescribing, with almost complete compliance and concurrent measurable reduction in day 3 nausea. SPC charts documented improvements in both outcomes. CONCLUSIONS SPC charts effectively monitor ongoing compliance and patient symptoms and represent appropriate outcome measurement and change facilitation tools. However, physician participation in guideline development and evidence of poor compliance alone did not improve prescribing performance. Only evidence of patient CINE experience coupled with noncompliance improved results.

Transplantation of unrelated cord blood cells

A 43-year-old woman with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in acute phase received high-dose chemotherapy followed by transfusion of 12 randomly selected units of umbilical cord blood. HLA analysis showed cells of one donor from day +10 to day +43 post-transfusion. This unit was HLA class II identical with that of the patient.

Adjuvant adriamycin and cis‐diamminedichloroplatinum (cis‐platinum) in primary osteosarcoma

Twelve consecutive patients with osteosarcoma who were without evidence of metastases were treated with Adriamycin and cis‐platinum in an adjuvant fashion. The primary lesion was in the distal femur in five patients, proximal tibia in three, and one each in the proximal femur, proximal humerus, sacrum, and a previously irradiated orbit.

Hydroxyethyl Starch and Dexamethasone as an Adjunct to Leukocyte Separation with the IBM Blood Cell Separator

A total of 67 leukaphereses were performed with the IBM blood cell separator (BCS) on 50 healthy donors for the purpose of obtaining a clinically useful number of granulocytes for infusion into patients with acute leukemia and granulocytopenia accompanied by severe infection. The pretreatment of donors with dexamethasone and the addition of hydroxyethyl starch (HES) to the input line of the BCS significantly increased the total number of granulocytes collected, as compared to the total number of granulocytes harvested either by dexamethasone pretreatment only or by the absence of dexamethasone and HES. A mean of 2.03 × 1010, 1.58 × 1010, and 1.07 × 1010 total granulocytes was collected by the HES plus dexamethasone, by dexamethasone alone and with neither HES or dexamethasone, respectively. The efficiency of cell collection, as evidenced by the total number of granulocytes harvested per liter of blood processed, was also significantly improved by the combined use of HES and dexamethasone. The results of the present study demonstrates that a clinically useful number of granulocytes can be harvested and made available for supportive therapy to patients experiencing granulocytopenia caused by malignant disease or its treatment.

The Effect of a Single or Double Dose of Dexamethasone on Granulocyte Collection with the Continuous Flow Centrifuge

Abstract. A total of 33 leukaphereses were performed with the IBM continuous flow centrifuge on 28 normal healthy donors for the purpose of obtaining increased yields of granulocytes for infusion into leukopenic recipients. The pretreatment of donors within a 10‐ to 12‐hour period prior to pheresis with a double dose of dexamethasone and the addition of hydroxyethyl starch to the input line of the continuous flow centrifuge, significantly increased the total quantity and efficiency of granulocyte collected as compared to a donor group receiving a single dose of dexamethasone in addition to hydroxyethyl starch. A mean of 25.5 × 109total granulocytes were collected in addition to an efficiency of 2.11 × 109granulocytes harvested per liter of blood processed in the double‐dose‐treated donors, in contrast to 19.6 × 109total granulocytes collected and an efficiency of 1.82 × 109granulocytes harvested per liter of blood processed in the single dose donor group. The results of the present study demonstrate that elevated quantities of granulocytes can be collected from normal donors by scheduling a double dose of dexamethasone prior to the pheresis procedure.