Booster effect in delayed hypersensitivity skin testing.

After a pilot study had suggested that a drug augmented delayed hypersensitivity, we conducted a control study in which 19 normal volunteers had the same skin test battery applied as in the pilot study, on two occasions one month apart with no intervening treatment. No change was observed in delayed hypersensitivity response to PPD, Candida, or tetanus antigens. However, a significant decrease in response to mumps antigen was observed, and there was a marked "booster" or augmented response to SKSD antigen. These observations have implications for studies of immunomodulation and the mechanism of action of delayed hypersensitivity response.

Failure of cimetidine as an immunomodulator in cancer patients and normal subjects.

Our pilot study of cimetidine as an immunomodulator in cancer patients showed no effect at clinically used doses on total blood, neutrophil, lymphocyte, or monocyte count, quantitative immunoglobulin, percentage of E-rosetting cells, phytohemagglutinin responses or delayed hypersensitivity responsiveness. We concluded that in clinically used doses, cimetidine produces no significant immunomodulation either in vivo or in vitro.

Long-term relapse-free survival in adult acute lymphoblastic leukemia.

An intensive treatment program with curative intent was designed for adults with acute lymphoblastic leukemia (ALL). Forty-eight consecutive patients were treated with this protocol and 39 (81%) obtained a complete remission. Although the complete remission rate was high for patients with both null- and T-cell disease, those with null-cell leukemia had a significantly greater median duration of remission (greater than 306 weeks) than patients with T-cell disease (62 weeks). The median survival by life-table analysis for the 48 patients is projected to be greater than 310 weeks, and five patients have finished the 3-year treatment program and have been off therapy for 1-3 years without recurrence of disease. Classification of adult ALL by immune marker status is an important and easily done pretherapy maneuver that identifies subsets of patients with a significantly different prognosis when treated with the protocol described in this study. Those patients for whom leukemic cells had T-cell characteristics had a short median duration of remission. Most importantly, this treatment protocol identifies by therapeutic response a subset of adult patients with ALL whose leukemic blasts are characterized by the absence of immunological markers and who appear, in substantial proportion, to be potentially curable.

The effects of anti-leukemic therapy on gonadal histology in adult males.

Testicular histologic findings in 29 male patients who died of acute leukemia or blastic phase of chronic myelogenous leukemia are reviewed to evaluate the effect of therapy on morphology. Four histologic groups were identified that correlated with the duration of treatment: (1) normal testes associated with no therapy or therapy for less than 30 days; (2) maturation arrest in those treated for five days to 40 months; (3) hypospermatogenesis in those treated from 17 days to 84 months; and (4) Sertoli cells only in those treated from between three and 63 months. These histologic patterns correlated more with the duration of therapy than the type of anti-leukemic therapy used. There was some variability in the histologic effects among individuals receiving comparable durations and types of chemotherapy. In many patients who received extensive therapy, spermatogonia remain which may allow recovery of spermatogenesis and fertility.

A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia.

To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.

Function and morphology of platelets produced for transfusion by intermittent-flow centrifugation plateletpheresis or combined platelet-leukapheresis.

The effects on platelet function of intermittent-flow centrifugation pheresis were measured employing platelets collected from ten donors by combined platelet-leukapheresis with hydroxyethyl starch (LP) and from ten by plateletpheresis (PP) by similar techniques except without starch. Greater numbers of platelets were produced by LP than by PP. Aggregation of platelets collected by both LP and PP was normal (did not differ from prepheresis baseline) to collagen and to 10(-5)M adenosine diphosphate (ADP). Slight impairment to aggregation with 2 X 10(-6)M ADP and 5.5 X 10(-5)M epinephrine occurred with both techniques. These abnormalities, however, were significantly less severe in platelets collected by LP. Platelet morphology by electron microscopy was nearly normal, although glycogen granules were absent in LP platelets. Thus, hydroxyethyl starch, at doses currently used during a single LP, does not enhance abnormalities of platelet aggregation over those expected to result from PP alone. Actually, LP platelets function better in vitro than those collected by PP. Large numbers of platelets can be harvested by LP, and their use as a component that is comparable to PP platelets may mean improved efficiency and reduced costs for pheresis centers.

Platelet function in donors undergoing intermittent-flow centrifugation plateletpheresis or leukapheresis.

Platelet dysfunction and prolonged bleeding have been seen in man when glucose polymer solutions, such as dextran, are used to volume replacement. Hydroxyethyl starch (HES) is a glucose polymer slightly different from dextran, which is used as a sedimenting agent in leukapheresis procedures. This controlled study was performed to evaluate the effect of HES on platelet function in centrifugation leukapheresis donors. Plateletpheresis using the same machines and techniques but without HES was the control. Platelet function was assessed by bleeding time, platelet count, adhesiveness to glass beads and aggregation to collagen, epinephrine and several concentrations of ADP, before and after the pheresis procedures. Except for a decrease in platelet count after both procedures, no other major changes in platelet function were seen. After one exposure in previously unpheresed donors, HES does not induce platelet dysfunction.

cis-dichlorodiammineplatinum(II) with and without ICRF-159 in non-Hodgkin's lymphoma.

Two studies of cis-dichlorodiammineplatinum(II) (CDDP) were conducted. The single-agent phase II study revealed that three of ten patients with non-Hodgkin's lymphoma treated with CDDP alone achieved objective partial remission of 7-15 weeks' duration. Eight patients were treated with CDDP plus ICRF-159. None of these eight patients achieved an objected response. CDDP is active as a single agent in non-Hodgkin's lymphoma. The combination of CDDP plus ICRF-159 does not appear to be a promising salvage program for non-Hodgkin's lymphoma.

Effect of intermittent-flow centrifugation leukapheresis on donor leukocyte counts.

Effects of intermittent-flow centrifugation leukapheresis (IFCL) on leukocyte counts in donor blood have not been reported. Accordingly, total and differential white blood cell counts were preformed serially during IFCL. A significant decrease (p less than 0.05) in all types of leukocytes occurred in donor blood early in pheresis and was probably the consequence of hemodilution. Concentrations of most leukocyte types remained decreased throughout the procedure, and a rebound leukocytosis was not detected. Thus, leukocyte kinetics in donor blood during IFCL differ from those reported for filtration leukapheresis in which the pattern of selective neutropenia followed by rebound neutrophilia has been ascribed to complement activation.

Monitoring central nervous system methotrexate levels via subcutaneous reservoir. Sources of errors in sampling and their avoidance.

The Ommaya reservoir allows for ready, well-tolerated direct access to the intraventricular cerebrospinal fluid (CSF). The toxicities associated with central nervous system (CNS) methotrexate (MTX) therapy have been attributed to prolonged high levels of the drug. When samples of CSF are removed from a reservoir for the monitoring of MTX levels, there may be sampling errors introduced by retention of high concentrations of drug in the reservoir. Using an in vitro system we confirm this possibility and show that using different injection or sampling techniques will increase or decrease this error. Without proper sampling, particularly several days after the initial injection, one may overestimate the MTX level and may unnecessarily alter treatment. A simple method of avoiding this error is to flush the reservoir after drug injection with a small (3-5 ml) volume of CSF withdrawn prior to injection.

Gram-negative sepsis treated with neutrophils collected exclusively by intermittent flow centrifugation leukapheresis.

The effectiveness of neutrophils prepared for transfusion by intermittent flow centrifugation leukapheresis (IFCL) as treatment for serious bacterial infections in neutropenic patients has not been documented in the literature. Their value, in fact, has been questioned. We report that IFCL neutrophils are similar to cells prepared by other techniques in the ability to support neutropenic patients with culture-proven, gram-negative sepsis unresponsive to antibiotics.

Phase II study of cis-dischlorodiammineplatinum(II) in stage IVB Hodgkin's disease.

A broad phase II study of cis-dichlorodiammineplatinum(II) was conducted. Eight patients with stage IVB Hodgkin's disease were studied. Four of these patients attained an objective partial remission of 7--19+ weeks' duration. The usual time to the occurrence of a greater than 25% response was 1 week. This drug is active in far-advanced Hodgkin's disease with a projected lower limit of response rate from 19% to 21%.

Fertility and cancer therapy.

With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life.