Search PubMed⌕ Search

Biomedical subjects

J R Wingard

Publications and source records attributed to J R Wingard.

At least 127 records · Page 7Linked to original sources
PubMed1989

Cutaneous graft-versus-host reaction lacks evidence of cutaneous cytomegalovirus by the immunoperoxidase technique.

Sixty skin biopsy specimens from 21 bone-marrow transplant patients were evaluated for the presence of cytomegalovirus (CMV) using two monoclonal antibodies to early and late antigens. Each patient had at least one biopsy showing an acute graft-versus-host reaction (GVHR), grade 2, and one positive culture for CMV from blood, bone marrow or urine. In no case could CMV antigens be identified in biopsies showing an acute or chronic cutaneous GVHR or in any other of the skin biopsies obtained from these patients. While CMV may play a role in immunologic events culminating in graft-versus-host disease (GVHD), this immunoperoxidase study did not reveal evidence of viral antigens in tissue displaying features of cutaneous GVHR.

Biopsy↗
PubMed1989

Longitudinal changes in pulmonary function following bone marrow transplantation.

We prospectively followed a well characterized cohort of patients post-bone marrow transplantation for changes in pulmonary function. Thirty-four recipients without respiratory symptoms were available for follow up with a mean of two years. Spirometry and other measures of lung volume were well preserved following bone marrow transplantation. A progressive 11.9 percent decline in percent predicted diffusing capacity per year occurred. Age, cigarette smoking, type of cytoreductive therapy, type of GVHD prophylaxis, and the occurrence of AGVHD did not affect longitudinal changes in pulmonary function. Patients receiving transplants for CML developed a highly significant fall in diffusing capacity. Asymptomatic patients with CGVHD developed evidence of progressive obstructive ventilatory impairment. This suggests a subclinical spectrum of patients who may progress to the development of bronchiolitis obliterans and respiratory failure post-bone marrow transplantation.

Adult↗
PubMed1989

Herpes zoster infection after autologous bone marrow transplantation.

One hundred fifty-three patients who underwent autologous bone marrow transplant (ABMT) were studied retrospectively to determine the frequency, outcome, and risk-factors associated with varicella-zoster infections (VZV). Forty-three patients (28%) developed VZV infection after transplant. The median onset of infection was the fifth month, with 91% of cases occurring within the first year. Thirty-three patients (77%) had localized herpes zoster, and ten patients (23%) had varicella. Cutaneous dissemination developed in 15% of patients and probable visceral dissemination developed in 5%. Overall morbidity was 25% and included scarring, alopecia, postherpetic neuralgia, and neurologic dysfunction. There were no deaths from VZV infection. The majority of patients (79%) were treated with intravenous (IV) acyclovir. The only significant risk factor associated with VZV infection was the underlying disease. VZV infection occurred most frequently in patients with Hodgkin's and non-Hodgkin's lymphoma (46%) as compared with patients with leukemia (23%) or solid tumors (9%) (P less than .002). The frequency of VZV infection in ABMT patients appears to be comparable to that reported for allogeneic BMT patients and other immunocompromised patients.

Actuarial Analysis↗
PubMed1989

Allogeneic bone marrow transplantation after high-dose busulfan and cyclophosphamide in patients with acute nonlymphocytic leukemia.

Ninety-nine patients with acute nonlymphocytic leukemia (ANLL) received HLA-identical bone marrow transplants (BMTs) from sibling donors after preparation with high doses of busulfan and cyclophosphamide. Forty-nine patients were transplanted in first complete remission (CR), and 50 patients were transplanted in second and third CR and early relapse. Fifty-three received one of three regimens containing primarily low-dose cyclophosphamide (group I) for graft-v-host disease (GVHD) prophylaxis; since March 1983, 46 patients received intravenous (IV) cyclosporine (group II). After December 1983, only cytomegalovirus (CMV)-seronegative blood products were used in appropriate patients, and since April 1984 patients seropositive for herpes-simplex virus (HSV) and CMV received high-dose acyclovir prophylaxis. For patients transplanted in first CR, there was a significantly lower incidence of acute GVHD (P = .005) and deaths related to GVHD and interstitial pneumonitis (P = .001) in patients in group II. This was reflected in an improved Kaplan-Meier probability of disease-free survival (DFS) in the 22 patients transplanted in group II as compared with the 27 patients in group I (64% +/- 10% v 30% +/- 9%, P = .017). The probability of remaining in remission was slightly lower in group II (82% +/- 9% v 94% +/- 6%, P = .479). For patients transplanted in second and third CR and early relapse, the incidence of acute GVHD (P = .026) and deaths related to GVHD and interstitial pneumonitis was significantly lower in group II (P = .029); the probability of remaining in remission was also less (47% +/- 15% v 91% +/- 15%, P = .022). However, the probability of DFS was not significantly different between the two groups (26% +/- 10% v 35% +/- 18%, P = .957). We conclude that transplantation for patients in first CR who received IV cyclosporine therapy is effective treatment; patients with more refractory disease treated with the same cyclosporine regimen (group II) had a lower incidence of GVHD than those treated in group I, but survival did not improve because of an increase in the number of relapses and other nonleukemic complications.

Acute Disease↗
PubMed1989

Predictors of death from chronic graft-versus-host disease after bone marrow transplantation.

Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens.

Actuarial Analysis↗
PubMed1989

Association of hepatic veno-occlusive disease with interstitial pneumonitis in bone marrow transplant recipients.

Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.

Anemia, Aplastic↗
PubMed1988

Interstitial pneumonitis after allogeneic bone marrow transplantation. Nine-year experience at a single institution.

Of 386 patients with allogeneic bone marrow transplants (BMT) treated during a 9-year interval, 166 developed interstitial pneumonitis (IP). Idiopathic and cytomegalovirus (CMV) IP constituted 90% of the 113 cases in which tissue was examined. Risk factors for IP overall were acute graft-versus-host disease (AGVHD), remote transplant date, the diagnosis of leukemia, and GVHD prophylaxis with agents other than cyclosporine. Risk factors for CMV IP were pre-transplant CMV seropositivity, CMV excretion, age greater than 10 years, AGVHD, GVHD prophylaxis with agents other than cyclosporine, and a remote transplant date. Patients transplanted for aplastic anemia were at lower risk for idiopathic IP than those transplanted for leukemia. The incidence of IP in patients given busulfan plus cyclophosphamide was equivalent to that in patients receiving cyclophosphamide plus total body irradiation. The incidence of idiopathic IP remained constant over this 9-year period while CMV IP declined significantly.

Adult↗
PubMed1988

Interstitial pneumonitis following autologous bone marrow transplantation.

Interstitial pneumonitis (IP) occurred in 20 of 143 (14%) patients who received cytoreductive therapy followed by autologous bone marrow transplantation (BMT) as treatment for malignancy. IP occurred at a median onset time of 41 days (5 to 624 days). All but three of the episodes were fatal. Of the thirteen cases in which tissue was examined, half were idiopathic; the remainder were due to various infectious agents. The actuarial incidences of idiopathic (7%) and CMV IP (2%) in these marrow autograft recipients were lower than the incidences of idiopathic (19%) and CMV IP (17%) in comparably treated recipients of allogeneic BMT (P less than or equal to 0.001 for both comparisons).

Adolescent↗
PubMed1988

Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin's disease.

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.

Adolescent↗
PubMed1988

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation.

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).

Bone Marrow Transplantation↗
PubMed1988

Bronchiolitis obliterans in bone marrow transplantation and its relationship to chronic graft-v-host disease and low serum IgG.

The records of 549 bone marrow transplant (BMT) patients at The Johns Hopkins Oncology Center during a 9-year period were reviewed to determine the incidence of bronchiolitis obliterans (BrOb). Seven patients had BrOb. All seven died, and BrOb was a contributing cause of death in six patients. Only recipients of allogeneic BMT were at risk for developing BrOb (2% incidence). Three cases were incidentally discovered at autopsy in patients who died less than 120 days after BMT from ventilatory failure owing to interstitial pneumonitis. Four cases were patients who died greater than 120 days after BMT. Of this latter group, all had overt chronic graft-v-host disease (CGVHD). Among 120 day survivors of allogeneic BMT, 6% of those with CGVHD developed BrOb as compared with none of those without CGVHD (P = .008). Five percent of patients with reduced IgG levels at day 120 developed BrOb as compared with none of those with normal IgG (P = .04). The incidence of BrOb in 120-day survivors was 14% (4 of 29) in patients with both CGVHD and decreased serum IgG, whereas patients with CGVHD only (0 of 25), those with decreased IgG levels only (0 of 53), and those with no CGVHD and normal IgG levels (0 of 70) did not develop BrOb.

Adolescent↗
PubMed1987

Differences between first and subsequent fevers during prolonged neutropenia.

Fever during neutropenia before engraftment was studied in 86 consecutively treated patients undergoing allogeneic bone marrow transplantation. Eighty-four of the 86 patients experienced 132 febrile episodes. Only 26% of the patients had one fever which resolved with antibiotics. The rest required modification of antimicrobial therapy because of refractory fever (32%) or recurrent fevers (42%). The 121 fevers which occurred during neutropenia were analyzed to determine differences between first and subsequent fevers (79 and 42 episodes, respectively). The frequency of sepsis (23%) and defervescence (64%) did not differ between first and subsequent fevers. Presumed localized infection (PLI) was identified in 75% of first fever but in only 28% of subsequent fevers (P = 0.000002). Of the PLI identified, oropharyngeal mucosal disease accounted for 68% during first fever but only 38% during subsequent fevers (P = 0.02). Although sepsis in first fever was more frequently associated with PLI than sepsis in subsequent fevers (61% versus 10%, P = 0.01), overall, patients with PLI had a lower frequency of sepsis than those without (17% versus 32%, P = 0.04). Gram-negative pathogens were uniformly gentamicin sensitive in sepsis during first fever but were mostly gentamicin-resistant in sepsis during subsequent fevers (P = 0.01).

Adolescent↗
PubMed1987

Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole.

Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia.

Adolescent↗
PubMed1987

Allogeneic, syngeneic and autologous marrow transplantation in the acute leukemias and lymphomas--Baltimore experiences.

Allogeneic bone marrow transplants (BMT) in acute lymphoblastic leukemia following cyclophosphamide (Cy) and total body irradiation (TBI) has resulted in disease-free survival (DFS) for CR1, CR2, and CR3 of 10/18 (56%), 16/30 (53%) and 4/17 (24%), respectively. Median follow-up of survivors was 25-43 months. One relapse was seen in CR1, 1 in CR2, and 6 in CR3. Allogeneic BMT in acute nonlymphoblastic leukemia (ANLL) following busulfan (Bu) resulted in DFS for CR1, CR2 + CR3 + early relapse of 21/47 (45%) and 13/41 (32%), respectively. Median DFS of survivors of all groups together was 36 months. DFS of all patients 20 years or less was 15/27 (56%) and 19/61 (31%) for ages 21-46. Three relapses of 47 (6%) were seen in CR1 and 6/41 (15%) in subsequent remission and early relapse. BMT of autologous BMT with 4-hydroperoxy-cyclophosphamide (4-HC) purged marrow in ANLL in CR1 (5), CR2 (32) and CR3 (9) following Bu + Cy resulted in DFS of 19/46 (41%) for 1-67 months (median 15 months). Twenty patients with prior risk non-Hodgkin's lymphoma received 4-HC-purged marrow following Cy + TBI. DFS was 10/20 (50%) for 1.4-9.5 years (median 2.9 years).

Acute Disease↗
PubMed1987

Aspergillus infections in bone marrow transplant recipients.

Aspergillus infection was studied in patients admitted to the Bone Marrow Transplant (BMT) Service at the Johns Hopkins Oncology Center during a 9-year period. The overall incidence was 4% in 549 patients reviewed. The incidence at autopsy was 12% (21 of 174 patients autopsied). There was no difference in frequency of occurrence in allogeneic compared to autologous BMT recipients. However, all infections in autologous BMT patients (5 of 5) occurred during neutropenia before engraftment. In contrast, 16 of 17 infections in allogeneic BMT patients occurred after engraftment (p = 0.0002). This difference presumably related to differences in duration of neutropenia and immunodeficiency. Age, underlying disease, date of BMT, preparative regimen, remission status, prior treatment, interstitial pneumonitis and concomitant cytomegalovirus infection did not predispose patients to aspergillus infection. Different post-BMT immunosuppressive regimens did not affect the risk for aspergillus infection except that patients who were given cyclophosphamide plus methylprednisolone had a higher incidence of aspergillus infection than those given methotrexate (12% versus 1%, p = 0.03). Acute graft-versus-host disease imposed a slight risk for infection (p = 0.06).

Aspergillosis↗
PubMed1986

Antibiotic-resistant bacteria in surveillance stool cultures of patients with prolonged neutropenia.

The value of stool surveillance for antibiotic-resistant gram-negative bacteria was analyzed in 86 neutropenic bone marrow transplant patients. Twice-weekly specimens were inoculated onto culture medium containing gentamicin plus carbenicillin. The recovered organisms were identified to the species level and tested for antibiotic susceptibility. Forty-eight resistant organisms were recovered from 35 patients. Thirteen isolates persistently colonized patients. Escherichia coli (29%) and Pseudomonas aeruginosa (19%) were the most frequently recovered organisms. Although most organisms were recovered while patients were on antibiotics, 15 isolates, including eight of nine resistant P. aeruginosa, were detected before antibiotics were initiated. The duration of antibiotic use was longer for patients persistently colonized than for those not colonized (P = 0.03). Of the 15 resistant organisms which caused infection, 12 were detected in the surveillance cultures. Infections by antibiotic-resistant organisms occurred more frequently in patients colonized than in those not colonized (P = 0.006) and more frequently in patients persistently colonized than in those colonized only once (P = 0.01). The absence of colonization or persistent colonization correlated well with the absence of infection (negative predictive values of 94 and 91%, respectively).

Adolescent↗