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Biomedical subjects

E C Reed

Publications and source records attributed to E C Reed.

51 records · Page 3Linked to original sources
PubMed1991

Improved results of allogeneic bone marrow transplantation for advanced hematologic malignancy using busulfan, cyclophosphamide and etoposide as cytoreductive and immunosuppressive therapy.

Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02).

Adolescent↗
PubMed1990

Ganciclovir for the treatment of cytomegalovirus gastroenteritis in bone marrow transplant patients. A randomized, placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy of ganciclovir for the treatment of cytomegalovirus enteritis after bone marrow transplant. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Inpatient units of a cancer center. PATIENTS: Consecutive patients with biopsy-documented cytomegalovirus infection of the gastrointestinal tract. Cytomegalovirus was identified by culture or by immunohistologic or standard histologic analysis. INTERVENTIONS: Ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, or placebo, with dosage adjusted for decreases in renal function. Therapy was discontinued if the neutrophil count or creatinine clearance fell below preset criteria. MEASUREMENTS AND MAIN RESULTS: Virus cultures of throat, urine, and blood specimens were done before, 3 times weekly during, and weekly for 3 weeks after therapy. Endoscopy was repeated after treatment. Patients were examined, and blood counts, electrolytes, and renal and hepatic function were monitored during therapy. Ganciclovir recipients had cessation of oropharyngeal (P = 0.001) and urinary (P = 0.004) cytomegalovirus excretion and negative cultures of repeat esophageal specimens (P = 0.002) more often than placebo recipients. No difference existed in either clinical symptoms or endoscopic appearance between the groups after treatment. Cytomegalovirus pneumonia occurred in four patients who received ganciclovir and in six who received placebo. One ganciclovir recipient and four placebo recipients were withdrawn from treatment because of neutropenia, but there was no overall difference in the proportional decrease in leukocyte counts between groups. CONCLUSIONS: Although ganciclovir suppressed cytomegalovirus replication, 2 weeks of treatment was not associated with clinical or endoscopic improvement when compared with supportive care.

Adolescent↗
PubMed1989

Clinical patterns of cytomegalovirus disease after liver transplantation.

During a 43-month period, we performed 248 liver transplantations in 211 patients (127 adults and 84 children). Cytomegalovirus (CMV) disease was documented in 73 recipients (34.6%). Risk factors for CMV disease included donor CMV seropositivity, antilymphocyte therapy, and retransplantation. The mean time of occurrence of CMV disease was 38.3 days after transplantation, and the most frequent site of disease was the hepatic allograft. A total of 69 patients were treated with intravenous ganciclovir, with a prompt and lasting response documented in 51 (73.9%). The remaining 18 (26.1%) developed recurrent CMV disease, which was more common after primary CMV exposure. Cytomegalovirus disease was ultimately controlled by ganciclovir in 94.2% of cases. This disease occurs early after transplantation and can be related to well-defined risk factors. Although ganciclovir therapy is effective, preliminary experience with prophylaxis shows promise in reducing the incidence of CMV disease.

Adolescent↗
PubMed1988

Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants.

STUDY OBJECTIVE: To determine if the combination of ganciclovir and intravenous cytomegalovirus immunoglobulin is effective in patients with cytomegalovirus pneumonia after bone marrow transplant. DESIGN: Consecutive entry trial with treatment for a minimum of 14 days. PATIENTS: Consecutive sample of 25 patients with bone marrow transplants and cytomegalovirus pneumonia after transplant proven by open lung biopsy or bronchoalveolar lavage. Patients with abnormal renal function or concomitant infectious causes of pneumonia, or who were respirator-dependent at diagnosis, were not eligible. INTERVENTIONS: Induction treatment consisted of ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, and cytomegalovirus immunoglobulin, 400 mg/kg on days 1, 2, and 7 and 200 mg/kg on day 14. Ganciclovir dosage was adjusted for renal function. Patients who were improved but still symptomatic after 14 days were given maintenance treatment consisting of ganciclovir, 5 mg/kg once daily for an additional 14 days, and immunoglobulin, 200 mg/kg on day 21. Patients with clinical deterioration continued to receive induction doses. Ganciclovir therapy was discontinued if the neutrophil count fell below 500 X 10(6)/L for 2 consecutive days. MEASUREMENT AND MAIN RESULTS: Serial tests of renal and liver function, blood counts, and viral cultures of blood, throat, and urine were obtained 3 times a week. Thirteen of twenty-five (52%) patients (95% CI, 31 to 72) survived the initial episode of pneumonia. Viral excretion ceased in 17 of 23 (74%) patients treated more than 96 hours. Proven recurrences of pneumonia occurred in 3 patients and possible recurrences in 2 after treatment was stopped. Three patients developed neutropenia during induction therapy and 6 patients during maintenance therapy. CONCLUSIONS: Survival of 13 (52%) of 25 patients from the initial episode of cytomegalovirus pneumonia with the regimen of ganciclovir and cytomegalovirus immunoglobulin is significantly better (P less than 0.001) than the survival of 13 of 89 (15%) patients using previous antiviral regimens.

Acyclovir↗
PubMed1988

Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation.

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.

Acyclovir↗
PubMed1988

Ganciclovir treatment of cytomegalovirus infection of the gastrointestinal tract after marrow transplantation.

Ganciclovir, an acyclic nucleoside with improved activity against cytomegalovirus in vitro, was used to treat 15 marrow transplant patients with symptomatic cytomegalovirus infection of the gastrointestinal tract. Eleven of the 15 had improvement in one or more of their clinical signs or symptoms during treatment. No clinical relapses were observed. Viral excretion from throat, urine and blood stopped at a median of 6 days of treatment, but six patients had recurrence of viral excretion 7-25 days after treatment was stopped. The only toxicity was the development of reversible neutropenia in eight of 15 patients after 10-19 days of treatment. Neutropenia was not related to duration of treatment, plasma drug levels or to the neutrophil count at the beginning of treatment. Although treatment with ganciclovir may be associated with marrow suppression, the serious nature of gastrointestinal infection due to cytomegalovirus in the immunocompromised host, the antiviral effect and the possible clinical improvement observed in vivo, and the lack of other effective treatments justify further controlled studies with this agent in immunocompromised patients with serious cytomegalovirus infection.

Acyclovir↗
PubMed1987

Rapid diagnosis of invasive cytomegalovirus infection by examination of tissue specimens in centrifugation culture.

Two hundred eight tissue specimens from 81 patients were examined by centrifugation culture for the rapid diagnosis of invasive cytomegalovirus (CMV) infection. Results were compared with those obtained by both conventional viral cultures and histologic examination. CMV was identified by centrifugation culture in 52 (25%) specimens at 16 hours after inoculation, including 39 lung specimens and 12 gastrointestinal specimens. One additional esophageal specimen was positive (53 of 208 specimens; 25.5%) at 36 hours. In contrast, CMV was recovered from only 50 of these 53 specimens by conventional cell culture at a mean of 11 days after inoculation. Forty-three of the 208 specimens (20.5%) were positive for CMV when examined by histologic methods, including light microscopy and tissue immunofluorescence. All 43 were positive by centrifugation culture. Specimens that were positive by centrifugation culture but negative by histologic methods included three lung specimens and seven gastrointestinal specimens. The technic of centrifugation culture is more sensitive for diagnosis of invasive CMV infection by the examination of affected tissue than either conventional viral culture or histologic technics, including tissue immunofluorescence, and more rapid than conventional culture or routine histologic examination.

Antibodies, Monoclonal↗
PubMed1987

Immunosuppressive effects of ganciclovir on in vitro lymphocyte responses.

We evaluated the effect of ganciclovir on in vitro immune responses by lymphocytes from healthy individuals. At clinically relevant concentrations, ganciclovir inhibited proliferation responses to cytomegalovirus antigen and to phytohemagglutinin by greater than 50% but had no effect on production of interleukin-2 or gamma interferon to these stimuli or on cytotoxicity against cytomegalovirus-infected, HLA-mismatched target cells. These results showed that ganciclovir inhibits lymphocyte functions for which lymphocyte proliferation is required but does not affect lymphocyte responses that do not require DNA synthesis. Studies of the effect on the immune responses in patients receiving ganciclovir will be needed to determine in vivo correlates of these findings.

Acyclovir↗
PubMed1987

Treatment of cytomegalovirus infection.

CMV infection is a major cause of morbidity and mortality in the immune compromised host. Ganciclovir and phosphonoformate have in vitro and in vivo activity against human CMV, and controlled trials of both these drugs in immunocompromised patients have suggested their efficacy. However, drug toxicity, a high rate of relapse, and the high mortality of CMV pneumonia in marrow transplant patients are continued problems in the treatment of CMV infections.

Acyclovir↗