Treatment of aplastic anemia: results with bone marrow transplantation, antithymocyte globulin, and a monoclonal anti-T cell antibody.
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Adolescent↗
Biomedical subjects
D J Winston
Publications and source records attributed to D J Winston.
Safety and tolerance of recombinant leukocyte A interferon in bone marrow transplant recipients.
Five bone marrow transplant recipients with cytomegalovirus infections were treated with pure recombinant leukocyte A interferon produced by recombinant DNA technology from Escherichia coli. All five patients had documented interstitial pneumonia. The daily intramuscular dose of interferon ranged from 18 X 10(6) to 50 X 10(6) U; the mean duration of therapy was 11.0 days (range, 5 to 18 days). Two patients recovered, one improved, and two died. Clinical side effects (usually fever and chills) occurred in three patients. A 60% or greater reduction in the pretherapy peripheral granulocyte counts occurred in four patients, and four patients had a 37 to 80% reduction in their pretherapy platelet counts. Hematological toxicity was reversible, and there was no loss of marrow graft function. The toxicity of pure recombinant leukocyte A interferon in marrow transplants is similar to that of partially pure leukocyte interferon derived from human cells. Further controlled studies to establish the efficacy of recombinant leukocyte A interferon in marrow transplants are warranted but may be limited by hematological toxicity.
Adult↗
Successful treatment of spinal arachnoiditis due to coccidioidomycosis. Case report.
An unusual case is reported of a patient with spastic paraparesis who was found to have severe spinal arachnoiditis due to Coccidioides immitis. Despite an obstructive hydrocephalus and a spinal subarachnoid block, the patient was treated effectively with surgery (shunting) and antifungal therapy (amphotericin and ketoconazole). He remains asymptomatic 3 years after diagnosis. Aggressive surgical and medical treatment of coccidioidal infection of the central nervous system can be beneficial, even in patients with the worst prognosis.
Adult↗
Pneumococcal vaccination of recipients of bone marrow transplants.
A 14-valent pneumococcal vaccine was administered to 39 recipients of allogeneic bone marrow transplants, and their type-specific antibody responses were compared with normal control subjects. Preimmunization antibody levels in patients were twofold to 12-fold lower than those levels in control subjects for all serotypes. Mean postimmunization antibody levels for each serotype were also considerably lower in patients (range, 56 to 859 ng of antibody nitrogen per milliliter) than in control subjects (range, 727 to 5,626 ng/mL). Poor antibody responses were primarily associated with early vaccination after transplantation, corticosteroid therapy for graft-v-host disease and other illnesses, and the male sex. Antibody responses of patients not given corticosteroids and vaccinated more than seven months after transplantation improved with time after transplantation. Postvaccination infection occurred in five patients who were vaccinated early after transplantation. Pneumococcal vaccination has limited potential for providing protection in marrow transplant recipients except in the cases of those patients who are not receiving corticosteroids and are vaccinated more than seven months after transplantation.
Adolescent↗
Coagulase-negative staphylococcal bacteremia in patients receiving immunosuppressive therapy.
From January 1977 to June 1980, coagulase-negative staphylococci caused bacteremia in 22 (17%) of 130 patients receiving immunosuppressive therapy and were the most common cause of all bacteremias. Sixteen (73%) of the 22 patients had granulocytopenia, and eight were isolated in a laminar air-flow room. A Broviac or Hickman central intravenous (IV) catheter was present in 20 (91%) of 22 patients, and soft-tissue inflammation at the catheter exit site was a significant risk factor for bacteremia. Except for debilitating fevers and local mucocutaneous infections, there were no distinguishing clinical features in patients with bacteremia. Most infections responded to cefazolin sodium or vancomycin hydrochloride therapy; catheter removal was necessary in only seven patients. These data show that coagulase-negative staphylococci can be important pathogens in patients receiving immunosuppressive therapy, even when the patients are isolated in a laminar air-flow room, if normal mucocutaneous, host-defence barriers are interrupted by IV catheter-insertion or chemotherapy.
Adolescent↗
Use of intravenous immune globulin in patients receiving bone marrow transplants.
Patients undergoing bone marrow transplantation for acute leukemia or aplastic are a great risk for the development of interstitial pneumonia associated with the cytomegalovirus (CMV). Passive immunization with a CMV immune plasma has been found to be effective for the prevention of interstitial pneumonia after marrow transplantation. Because of the limited availability of high-titered CMV plasma, we studied the kinetics of CMV antibody in bone marrow transplant patients receiving immune globulin intravenous, 5%, in 10% maltose (IGIV). Several lots of IGIV had CMV radioimmunoassay (RIA) antibody titers (1:30,000) comparable to the CMV antibody titers in the CMV immune plasma. A single infusion of 20 cc/kg of IGIV produced a mean peak CMV RIA antibody titer of 1:9,500. This titer fell to 1:1,000 after seven days. These antibody titers were approximately two-to three-fold lower than the CMV RIA antibody titers achieved after a 10 cc/kg dose of the CMV immune plasma. Administration of IGIV at doses lower than 20 cc/kg produced correspondingly lesser increases in the CMV antibody titers of recipients. At all doses, IGIV was well tolerated and caused no significant biochemical abnormalities. Some patients experienced mild elevation of their serum glucose levels and asymptomatic glycosuria. We are presently evaluating the efficacy of IGIV (20 cc/kg given once every week) for the modification of CMV infection and prevention of interstitial pneumonia after bone marrow transplantation in a randomized, controlled study. The effects of IGIV on the incidence and outcome of bacterial, fungal, and other viral infections are also being analyzed.
Antibodies, Viral↗
Alveolar macrophage dysfunction in human bone marrow transplant recipients.
We studied the functional characteristics of alveolar macrophages obtained by segmental pulmonary lavage from allogeneic marrow transplant recipients without evidence of ongoing pulmonary infection. The macrophages were mostly of donor marrow origin as judged by Y body fluorescence and were morphologically normal, except for the intracellular accumulation of various amounts of heterogeneous foreign materials. Macrophage function of patients studied within four months after transplantation was impaired, as measured by chemotaxis, phagocytosis and killing of Candida pseudotropicalis, and killing of bacteria. In two patients studied six and 12 months after transplantation, macrophage functions returned toward normal except for a persistent defect in killing of C. pseudotropicalis. Cytomegalovirus was cultured from the lavaged cells of two patients, but the macrophage dysfunction was independent of the cytomegalovirus isolation. These results show that alveolar macrophage dysfunction occurs in marrow transplant recipients and may be associated with their increased risk for pulmonary infections.
Acute Disease↗
Cytomegalovirus immune plasma in bone marrow transplant recipients.
The effects of passive immunization on cytomegalovirus infection and interstitial pneumonia in marrow transplants were evaluated in a randomized, controlled trial. Twenty-four patients received cytomegalovirus immune plasma before and after transplantation, and 24 patients were controls. Although the incidence of cytomegalovirus infection was similar in the control and plasma groups, symptomatic infection (12 of 24 versus five of 24, p = 0.07) and interstitial pneumonia (11 of 24 versus five of 24, p = 0.12) occurred less frequently in the group receiving plasma. Cytomegalovirus infection occurred in 11 of 13 recipients of leukocyte transfusions and in 16 of 35 patients not given leukocyte transfusions (p = 0.02). Among patients not given leukocyte transfusions, the incidence of cytomegalovirus infection was similar in the control and plasma groups, but symptomatic infection (eight of 18 versus one of 17, p = 0.03) and interstitial pneumonia (nine of 18 versus one of 17, p = 0.01) were significantly less in the group receiving plasma. These results suggest that passive immunization modifies cytomegalovirus infection in humans and prevents interstitial pneumonia in marrow transplants especially when leukocyte transfusions are not used.
Adolescent↗
Therapeutic granulocyte transfusions for documented infections. A controlled trial in ninety-five infectious granulocytopenic episodes.
Patients with granulocytopenia (granulocyte count less than 0.5 x 10(9)/L) and a documented infection were randomized to receive or not to receive daily granulocyte transfusions in addition to antimicrobial therapy. Thirty-four of 47 control patients responded to therapy compared to 30 of 48 transfused patients (type 2 error, pneumonia, or a soft tissue infection, respective response rates for the control and transfused patients were 11 of 11 and 11 of 16 (Yates' corrected chi-squared test, p = 0.12). Response rates for patients with gram-negative septicemia were lower but were influenced by recovery of bone marrow function. Eleven of 12 control patients and seven of seven transfused patients with recovery of marrow function survived the gram-negative septicemia. In contrast, 12 of 24 control patients and 12 of 25 transfused patients survived gram-negative septicemia and persistent granulocytopenia (type 2 error p = 0.13). Two thirds of all fatal infections were associated with an underlying disease refractory to medical therapy. Therapeutic granulocyte transfusions had no substantial benefit over optimal antimicrobial therapy alone in managing infected patients with granulocytopenia.
Abscess↗
Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.
In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.
Adolescent↗
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.
Bacterial Infections↗
Comparative in vitro synergistic activity of new beta-lactam antimicrobial agents and amikacin against Pseudomonas aeruginosa and Serratia marcescens.
The in vitro synergistic activities of moxalactam, cefoperazone, or cefotaxime in combination with amikacin or piperacillin were compared against aminoglycoside-susceptible and aminoglycoside-resistant isolates of Pseudomonas aeruginosa and Serratia marcescens by the checkerboard agar dilution method. All antimicrobial combinations demonstrated some synergy, and no antagonism was observed. Moxalactam plus amikacin and piperacillin plus amikacin were most frequently synergistic (two-thirds of the isolates inhibited synergistically by each combination), whereas combinations of moxalactam, cefotaxime, or cefoperazone with piperacillin were synergistic against only 18 to 25% of the isolates. Moxalactam plus amikacin was the combination most often synergistic for amikacin-susceptible P. aeruginosa, and piperacillin plus amikacin was the combination most frequently synergistic for amikacin-resistant P. aeruginosa and amikacin-susceptible S. marcescens. These results demonstrate frequent in vitro synergistic activity between the new beta-lactam agents and amikacin (especially moxalactam or piperacillin with amikacin), but comparative clinical trials are needed to establish the relative efficacy and toxicity of these combinations.
Amikacin↗
Prophylactic granulocyte transfusions during chemotherapy of acute nonlymphocytic leukemia.
Forty-six noninfected patients undergoing induction chemotherapy for acute nonlymphocytic leukemia were randomized to receive (25 patients) or not to receive (21 control patients) prophylactic granulocyte transfusions when their granulocyte count fell below 0.5 X 10(9)/L. Septicemia was less frequent in the patients who received transfusions (two in 25 patients) than in the control patients (five in 21 patients), but this difference was not statistically significant (p = 0.28). Moreover, pneumonia was more frequent among the transfused patients (12 in 25 patients versus two in 21 patients, p = 0.01). There were no significant differences between the two groups in the frequency of other documented infections, the achievement or duration of remission, or survival. Recipients of prophylactic granulocyte transfusions had a higher prevalence of cytomegalovirus infections (13 in 21 patients versus five in 19 patients, p = 0.03). These results suggest that prophylactic granulocyte transfusions have no statistically significant effect on the frequency of septicemia or other infections, do not enhance remission rates or survival, and are associated with an increased risk for pulmonary complications and cytomegalovirus infections.
Adolescent↗
Moxalactam therapy for bacterial infections.
Moxalactam, a novel beta-lactam antimicrobial agent in which oxygen has replaced sulfur in the six-membered ring of the conventional cephem nucleus, has in vitro activity against almost all commonly isolated bacterial pathogens including Staphylococcus aureus, the Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides fragilis, and Haemophilus influenzae. The clinical efficacy an toxicity of moxalactam alone was evaluated in the treatment of 100 infections, including 22 septicemias. Thirty-two infections involved P aeruginosa, while organisms resistant to one or more of the currently available cephalosporins or cefoxitin were isolated from cultures in 63 of the cases. The overall clinical response was favorable (infection cured or improved) in 86% of the infections. A child with Klebsiella pneumoniae ventriculitis and meningitis was cured with intravenous moxalactam alone. Six of 14 treatment failures involved P. aeruginosa, and P aeruginosa isolates resistant to moxalactam emerged during therapy of 12 infections. Side effects, usually mild diarrhea, occurred in only 8.8% of the patients. Except for some severe P aeruginosa infections outside the urinary tract, moxalactam is effective and safe single-agent therapy for infections caused by susceptible organisms and represents a major advancement in beta-lactam antimicrobial therapy.
Adolescent↗
Pneumocystis carinii pneumonia.
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Animals↗
Prophylactic granulocyte transfusions during human bone marrow transplantation.
Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients.
Adolescent↗
Piperacillin therapy for serious bacterial infections.
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Adult↗
Comparative in vitro activity of moxalactam, cefotaxime, cefoperazone, piperacillin, and aminoglycosides against gram-negative bacilli.
The in vitro activities of four new beta-lactam antimicrobial agents (moxalactam, cefotaxime, cefoperazone, and piperacillin) and the aminoglycosides against 744 recent clinical isolates of facultative gram-negative bacilli were compared simultaneously by the agar dilution method. The major in vitro difference of these newer beta-lactam compounds appeared to be their antipseudomonal activity; cefoperazone was the most active, whereas cefotaxime had the least potency. The aminoglycosides, however, had the most effective in vitro activity on a weight basis against Pseudomonas aeruginosa.
Aminoglycosides↗