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Biomedical subjects

J R Wingard

Publications and source records attributed to J R Wingard.

At least 109 records · Page 6Linked to original sources
PubMed1992

Growth in children after bone marrow transplantation: busulfan plus cyclophosphamide versus cyclophosphamide plus total body irradiation.

Growth was assessed during the first and second years following bone marrow transplantation (BMT) in 47 children treated by either busulfan plus cyclophosphamide (BU/CY) (n = 24) or cyclophosphamide plus fractionated total body irradiation (CY/TBI) (n = 23). Before transplant, the median height was only 0.2 SD below age- and sex-adjusted means (range, -2.5 to +3.0). Height was greater than 2.0 SD below normal in only three patients (6%). The pretransplant heights were comparable in the BU/CY and CY/TBI groups (-0.1 v -0.6 SD, P = .35). Following transplant, median 1- and 2-year heights were 0.7 and 0.9 SD below normal, respectively. Growth rates were 2.2 SD and 1.4 SD below normal during the first and second years, respectively. Growth rates were greater than 2.0 SD below normal in 24 of 47 (51%) at 1 year and in 12 of 31 (39%) at 2 years after transplant. Growth rates in patients treated with BU/CY were comparable to those treated with CY/TBI during both years: -2.5 versus -1.7 SD during the first year (P = .19, Wilcoxon), and -1.5 versus -1.1 SD during the second year (P = .61). Growth rates during the second year correlated with growth rates during the first year (r = .36, P = .046). Growth rates during the first year were lower in patients who had been given prior cranial irradiation, those who were near pubertal age at the time of transplant, and those who were transplanted for a disease other than acute lymphoblastic leukemia (ALL). During the second year, poor rates of growth were associated only with the use of corticosteroids after transplant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Bone marrow transplantation of chronic myelogenous leukemia in chronic phase: evaluation of risks and benefits.

PURPOSE: Allogeneic bone marrow transplantation (BMT) is an option for some patients with chronic myelogenous leukemia (CML). We retrospectively evaluated the effect of various risk factors observed at diagnosis and at transplantation on survival, event-free survival (EFS), and relapse after BMT. PATIENTS AND METHODS: Seventy-nine patients with CML in chronic phase (CP) were treated with cyclophosphamide and total body irradiation followed by BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CsA) in most instances or CsA plus the use of lymphocyte-depleted bone marrow (BM). RESULTS: Survival at 4.5 years was 52%. Stratified by age and GVHD prophylaxis, the actuarial survival was 65% (95% confidence interval [CI], 47% to 78%) in patients aged less than 30 years receiving unmanipulated BM, 33% (95% CI, 12% to 56%) in patients greater than or equal to 30 years old receiving unmanipulated BM, and 38% (95% CI, 14% to 63%) in patients greater than or equal to 30 years old receiving lymphocyte-depleted BM. In univariate analysis, patient age (greater than or equal to 30 years) and the use of lymphocyte-depleted BM negatively influenced EFS. When stratified by age and GVHD prophylaxis, however, ABO incompatibility, cytomegalovirus (CMV) seropositivity, and chronic GVHD significantly reduced the probability of EFS. Factors that have been associated with early death in nontransplanted patients (ie, sex, spleen size, blast and platelet counts at presentation) were not predictive of long-term survival outcome after BMT. CONCLUSIONS: The data suggest that (1) BMT should be offered early after diagnosis to all patients with CML in CP who have compatible sibling donors regardless of prognostic factors at presentation, (2) GVHD remains the principal cause of mortality after BMT in patients receiving CsA, and (3) T-cell depletion by the physical separation method of counterflow elutriation (CE) is associated with a significant risk of relapse.

Adolescent↗
PubMed1992

The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia.

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Amphotericin B↗
PubMed1992

Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice.

Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used extensively in clinical bone marrow transplantation (BMT), but the effects of high-dose administration have not been previously evaluated in preclinical BMT settings with young murine recipients. We compared the survival and growth of C57BL/6 mice given graded single doses of busulfan (10-100 mg/kg) or total body irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The 30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and 79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100 mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of 10-week-old mice given HCT after lower doses of busulfan ranged from 87% of control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg busulfan or TBI. Impairment of weight gain was most striking (approximately 50% of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation of somatic growth, the brain weights of busulfan-conditioned mice remained at least 90% of control, and there were no obvious neuropathological alterations in the brains of these animals. All mice treated with at least 20 mg/kg busulfan or TBI lost hair by 3-4 weeks after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sexual satisfaction in survivors of bone marrow transplantation.

Of 157 (80%) adult survivors of bone marrow transplantation, 126 responded to a mailed survey 6-149 months after transplant concerning their ability to attain sexual satisfaction. Sixty-five percent of the subjects indicated some degree of sexual satisfaction (with 29% indicating a high degree of satisfaction). Thirteen percent were neutral and 22% were dissatisfied. Gonadal physiological disturbances were present in most subjects as a result of intensive treatments. Fifty-seven percent of women were receiving estrogen replacement, and only 40% had regular menses. Twenty-four percent of men had difficulty with erections and 13% had ejaculatory dysfunction. For men, difficulties with erection (r = 0.54, p less than 0.001) or ejaculation (r = 0.52, p less than 0.001) were associated with inability to attain sexual satisfaction. For women, loss of menses (r = 0.34, p = 0.008) was associated with inability to attain sexual satisfaction. Although few women had abnormally low serum estradiol (even with hormonal supplementation), and none of the 43 men tested had abnormally low serum testosterone, sexual satisfaction correlated with serum levels of estrogen in women (r = 0.42, p = 0.04) and serum testosterone in men (r = 0.28, p = 0.04). Forty-two subjects rated their level of sexual satisfaction before and after transplant. Post-transplant satisfaction was not associated with pretransplant satisfaction (r = 0.07, p = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole.

BACKGROUND: In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants. METHODS: To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990. RESULTS: The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro. CONCLUSIONS: In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.

Adult↗
PubMed1991

Health, functional status, and employment of adult survivors of bone marrow transplantation.

OBJECTIVE: To determine the health, functional ability, and employment status of adults who survive bone marrow transplantation. DESIGN: Inception cohort study. SETTING: Patients who received transplants at a single referral-based center. PATIENTS: Adults of 18 years of age or older who had received bone marrow transplants at least 6 months previously and who were not in a life-threatening relapse were surveyed a mean of 47 months after transplant (median, 37 months; range, 6 to 149 months). Of 171 eligible patients, 157 were contacted and 135 (86%) responded. MEASUREMENTS AND MAIN RESULTS: Patients completed a mailed survey. Medical records were also reviewed. Most patients (93%) reported they could do normal activities with minor or no physical problems (Karnofsky scores, greater than or equal to 80%). Global health was described as good to excellent by 67% of subjects. Most perceived social activities (80%) or physical functional abilities (67%) to be unimpaired or only slightly affected. Moderate or severe pain was uncommon (13%). Sixty-five percent had returned to full- or part-time employment, and one third of those who were not employed were attending school. Job discrimination and problems in obtaining insurance were reported by 23% and 39%, respectively. Among those who had been employed before illness, loss of employment was associated with lower social functioning, chronic graft-versus-host disease, greater job discrimination, and female gender using multivariate logistic regression. CONCLUSIONS: Most subjects surviving bone marrow transplant reported good to excellent health and functional ability. Three fourths were employed or enrolled in school. These outcomes are comparable to outcomes in survivors of cancer who received less intensive treatments.

Activities of Daily Living↗
PubMed1991

Oral mucositis after bone marrow transplantation. A marker of treatment toxicity and predictor of hepatic veno-occlusive disease.

Oral mucositis and hepatic veno-occlusive disease (HVOD) are common complications after bone marrow transplantation (BMT). Forty-seven patients were prospectively examined for development of ulcerative oral mucositis (UOM) and HVOD after allogeneic BMT. In 17 patients (36%) UOM developed between 2 days before and 18 days after transplant (median 4 days after BMT). In seven patients (15%) HVOD developed with onset between 3 and 21 days after transplant (median 18 days after BMT). In a time-dependent analysis, in patients given busulfan plus cyclophosphamide or busulfan, etoposide, and cyclophosphamide UOM was 19 times more likely to develop than in patients treated by cyclophosphamide plus total body irradiation or by cyclophosphamide alone (p less than 0.001). Patients in whom UOM developed were 6.5 times more likely to develop HVOD than those in whom UOM did not develop (p less than 0.03). The sensitivity (86%), specificity (73%), and negative predictive value (97%) of UOM to predict HVOD were high, but the positive predictive value (35%) was low. The association of UOM and HVOD support the concept that both are toxic effects of treatment. Patients with hepatic abnormalities but without UOM are unlikely to have HVOD, and other causes of the hepatic dysfunction should be investigated.

Adolescent↗
PubMed1991

Role retention and quality of life of bone marrow transplant survivors.

Bone marrow transplantation (BMT) offers the potential for survival of 50% or more for selected patients with malignant disease not controlled by other means. However, BMT introduces risks for psychological, social, and physical impairment and the potential for significant loss in one's ability to retain important role relationships. While there has been a sharp increase in the performance of BMTs in the past decade, there has been little research on its effects on long-term survivors. This paper presents the results of a follow-up survey of 135 survivors of BMT at the Johns Hopkins Oncology center. The ability of the survivors to maintain valued social roles is examined as this affects perceived quality of life. The main hypothesis of the paper, that role retention is significantly related to higher quality of life, is supported by significant correlations of role retention with quality of life as measured by the Satisfaction with Life Domains Scale, current and future life satisfaction on Cantril Self-Anchoring Ladders, and by the Bradburn Positive Affect Scale. While the Bradburn Negative Affect Scale was not significantly related to role retention, total negative mood as measured by the Profile of Mood States was inversely related to role retention at a statistically significant level.

Adaptation, Psychological↗
PubMed1991

Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity.

Bone marrow transplantation has become widely used in the treatment of aplastic anemia and leukemia. Cyclosporine is used as prophylaxis against graft-versus-host disease. The authors report on eight cases of optic disc edema in patients taking cyclosporine after allogenic bone marrow transplant. Thorough evaluation revealed a possible alternate cause in two cases. In all cases, the optic disc edema resolved after discontinuing or decreasing the cyclosporine. Although cyclosporine has not previously been associated with optic disc edema, it has been implicated as the cause of a variety of neurologic side effects. Bone marrow transplant patients taking cyclosporine should be followed for the development of optic disc edema.

Adolescent↗
PubMed1991

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

Adolescent↗
PubMed1990

Orthotopic liver transplantation for graft-versus-host disease following bone marrow transplantation.

Chronic graft-vs.-host disease occurs in 30%-50% of long-term survivors of allogeneic bone marrow grafts, and may eventuate in cirrhosis. In this study, a young woman, originally diagnosed as having acute myelogenous leukemia, underwent successful bone marrow transplantation but later developed graft-vs.-host disease-induced cirrhosis and recurrent variceal hemorrhage. She underwent successful orthotopic liver transplant. Her postoperative course was uncomplicated, with no evidence of rejection or recurrence of graft-vs.-host disease. As bone marrow transplantation is more widely used and survival improves, the number of patients with graft-vs.-host disease or venoocclusive disease resulting in cirrhosis is likely to increase. Hepatic transplantation should be considered for bone marrow transplant patients who develop end-stage liver disease.

Adult↗
PubMed1990

Coaggregation of oral Candida isolates with bacteria from bone marrow transplant recipients.

In vitro coaggregation between Candida species isolated from immunosuppressed bone marrow transplant recipients and oral bacteria was investigated. Each Candida strain showed a different pattern of coaggregation with the 22 bacterial strains studied. Two strains of Lactobacillus amylovorus isolated from separate bone marrow transplant patients and Fusobacterium nucleatum (VPI 10197) coaggregated with all Candida strains. Ten bacterial strains showed no coaggregation with the Candida strains. A variety of inhibition patterns were observed when coaggregating strains were first incubated with various sugars or subjected to heat treatment. Positive and negative results were generally consistent with all Candida strains. On the basis of the culture characteristics of the oral rinse specimens, relationships between the colonization of bacteria and yeasts and in vitro coaggregation were suggested.

Bacteria↗
PubMed1990

Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia.

Seventy-four consecutive patients with high-risk acute lymphoblastic leukemia (ALL) were given cyclophosphamide (CY; 50 mg/kg on each of 4 days) plus total body irradiation (TBI; 300 rad on each of 4 days) followed by a human leukocyte antigen (HLA)-identical allogeneic bone marrow transplant (BMT). Eighteen patients in first complete remission (CR1), 36 in CR2, 16 in CR3, and four in CR4 were transplanted. Patients in CR1 were transplanted 1 to 8 months (median, 3 months) after attaining CR. All 18 patients in CR1 had one or more poor risk factors: age more than 18 (N = 17), initial leukocyte count greater than or equal to 20,000 (N = 11), Ph 1 chromosome (N = 2), delay in attaining CR more than 6 weeks (N = 8), or extramedullary disease (N = 1). Of those transplanted in CR2, 72% had relapsed on therapy. The 5-year event-free survival (EFS) rates for patients transplanted in CR1, CR2, and CR3 are 42%, 43%, and 25%, respectively, at median follow-up times of 57, 54, and 72 months, respectively. Children aged less than 18 years transplanted in CR2 have a 5-year EFS rate of 54%. All CR4 patients died early after transplant. The actuarial probability of relapse is 20%, 26%, and 48% for those transplanted in CR1, CR2, and CR3, respectively. Although there was substantial transplant-associated mortality, it decreased over the decade of the study (P = .01). This study indicates that BMT offers an attractive alternative to postremission chemotherapy in patients in CR1 with poor prognostic factors and in patients in second remission.

Adolescent↗
PubMed1990

Advances in the management of infectious complications after bone marrow transplantation.

An important contribution to the improved survival after bone marrow transplantation (BMT) over the past decade has been the development of strategies to prevent and manage infectious complications. Today, with these advances, deaths from bacterial and fungal infections are uncommon except in the setting of uncontrolled graft-versus-host disease (GVHD) or failure of engraftment. Historically, the major life-threatening pathogens have been viruses, especially the herpesvirus family. However, they too have become less deadly with the introduction of antiviral agents, changes in transfusion strategies, improvements in the control of GVHD, and better diagnostic procedures. With improved detection methods, we now recognize that some complications formerly thought to be due to treatment toxicities are caused by infectious pathogens. We are increasingly recognizing the complex interplay between immunodeficiency, tissue damage, infectious pathogens, and disordered immune responses. This greater knowledge in time should improve our understanding of the biology of BMT as well as result in improved outcomes.

Anti-Infective Agents↗
PubMed1990

Management of infectious complications of bone marrow transplantation.

Following bone marrow transplantation, patients are profoundly immunodeficient and susceptible to a variety of opportunistic infections. The types of infections vary during different intervals after transplantation. Before engraftment, neutropenia and damaged mucosal surfaces are the predominant deficits in host defenses against infection, and bacterial and fungal infections are the most common infections encountered. During the early post-engraftment period, acute graft-versus-host disease and its treatment result in a severe deficiency of cellular immunity. Cytomegalovirus infection is frequent and can result in life-threatening pneumonia. Fungal infections are also common. After the first three months, infection is much less common. However, reactivation of varicella-zoster virus (VZV) and infections with certain pathogens such as Pneumocystis carinii, can occur due to still-impaired cellular immunity.

Bone Marrow Transplantation↗
PubMed1990

Oral complications of cancer therapies. Infectious and noninfectious systemic consequences.

Oral complications of cancer therapy often have systemic consequences. Pain and discomfort are common and can lower intake of fluid and nutrients, which in severe cases can lead to dehydration and malnutrition, requiring hospitalization. Oral infections are frequent accompaniments of cancer treatment. Herpes simplex virus is the most common symptomatic oral viral infection, and, in latently infected patients the virus is frequently reactivated after cytoreductive therapy. Viral (infectious) oral mucositis is often indistinguishable from noninfectious mucositis. Bacterial infections are less commonly observed today, perhaps because of the routine use of empiric broad-spectrum antibiotics; however, many episodes of septicemia in neutropenic patients apparently originate from oral microorganisms. Fungal infections are frequent and are usually due to Candida species. Spread to the esophagus or systemic dissemination can occur. Noninfectious oral mucositis can be used as a marker of toxic effects in other organs, especially hepatic veno-occlusive disease. In bone marrow transplant patients with mucositis, hepatic veno-occlusive disease is six times more frequent than in such patients without mucositis.

Bacterial Infections↗