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Biomedical subjects

K M Sullivan

Publications and source records attributed to K M Sullivan.

At least 181 records · Page 10Linked to original sources

What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?

One hundred forty-seven consecutive patients with leukemia, myelodysplastic syndrome, or aplastic anemia were treated by marrow grafts from genotypically HLA-identical siblings (n = 122) or HLA-haploidentical family members (n = 25). Haploidentical recipients differed from their donors for no more than one HLA locus on the nonshared haplotype. All were given postgrafting immunosuppression with a combination of methotrexate and cyclosporine. In a randomized study we explored whether prednisone administered from day 0 through 35 along with methotrexate/cyclosporine could improve prevention of acute graft-versus-host disease (GVHD). The GVHD incidence in patients not given prednisone was comparable with that previously reported with methotrexate/cyclosporine. Unexpectedly, significant increases in acute and also chronic GVHD were seen in HLA-identical recipients administered prednisone, but not in the small number of patients administered HLA-nonidentical grafts. However, the resultant increase in transplant-related mortality in patients administered prednisone was offset by an increase in leukemic relapse in patients not administered prednisone, presumably related to the absence of a graft-versus-leukemia effect. Therefore, overall disease-free survival of the two groups of patients was comparable, with slightly more than 50% of the patients being alive at more than 2 years after transplantation. We speculated that prednisone adversely affected GVHD prophylaxis, interfering with methotrexate's cell cycle-dependent suppression of donor lymphocyte proliferation in response to host antigens. In a pilot study we explored whether beginning prednisone on day 15, after completion of methotrexate administration, would avoid this adverse effect. The GVHD incidence in patients administered methotrexate/cyclosporine along with "late" prednisone was comparable with that in patients not administered prednisone. We conclude that methotrexate/cyclosporine is effective in decreasing the incidence of grade II through IV GVHD, and that the addition of prednisone to this regimen is not beneficial in recipients of HLA-identical marrow grafts.

Acute Disease↗

Supportive care of the marrow transplant recipient: the Seattle Experience.

It is now almost 2 decades after the first successful human marrow transplants from HLA-identical siblings for the treatment of life-threatening hematologic diseases. Results have improved, especially for patients transplanted earlier in the course of disease. However, major problems remain in supporting patients through the transplant. More effective and less toxic conditioning regimens are needed. Acceleration of hematopoietic and immunologic reconstitution by use of various cytokines holds promise for decreasing infectious morbidity and mortality. Improved regimens to control acute and chronic GVHD and prevent opportunistic infections will play a major role in the advancement of supportive care of the marrow transplant recipient.

Anti-Infective Agents↗

Macrosomia: influence of maternal overweight among a low-income population.

Macrosomia (birth weight greater than 4000 gm) is associated with a wide variety of adverse intrapartum and perinatal outcomes. To evaluate the effect of pregravid obesity on infant birth weight, we examined data from a low-income population of women (n = 127,879). The population was divided into five groups on the basis of pregravid body mass index (weight/height) designated by the National Health and Nutrition Examination Survey II reference population (less than 25th percentile, 25th to less than 75th percentile, 75th to less than 85th percentile, 85th to less than 95th percentile, and greater than or equal to 95th percentile). The prevalence of infant macrosomia ranged from 5% for the lowest group to 17% for the highest group. With the use of the second group (25th to less than 75th percentile) as a reference, odds ratios (adjusted for maternal age, smoking status, race, height, parity, gestational age, and infant sex) for macrosomia for the five sequential weight groups were 0.6, 1.0, 1.3, 1.6 and 2.2. We conclude that pregravid overweight had a significant independent effect on birth weight outcome.

Adolescent↗

Antibody response to inactivated influenza vaccines of various antigenic concentrations.

Four inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/H1N1 antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the A/H1N1 and B antigens (adjusting for the prevaccination antibody titer and antigen content).

Adult↗

Use of the confidence interval function.

Graphics displaying all confidence intervals around a point estimate have been referred to as P-value functions and consonance intervals. We recommend use of the term confidence interval function (CI function) rather than P-value function. The CI function is useful because it simultaneously depicts point estimation, variability, and the relation of these two factors to the null value. The usefulness of the CI function in demonstrating the concepts of effect modification and confounding, in meta-analysis, and in the comparison of various confidence interval procedures is evaluated. Software packages that produce CI functions are described.

Confidence Intervals↗

Previous donor pregnancy as a risk factor for acute graft-versus-host disease in patients with aplastic anaemia treated by allogeneic marrow transplantation.

To determine if previous donor pregnancies influence the development of acute graft-versus-host disease (GVHD) we evaluated data from 136 patients with aplastic anaemia greater than 15 years of age and given marrow grafts from HLA-identical sibling donors. Of the 136 marrow donors, 30 were parous females (previous history of pregnancy), 30 were nulliparous females (no history of pregnancy or abortions), and 76 were males. The cumulative incidence of grade II-IV GVHD was 57%, 21% and 46% for patients with parous, nulliparous and male donors, respectively. A multivariate analysis of the data confirmed that the risk of grade II-IV acute GVHD was significantly increased among patients receiving marrow from parous females as compared to those from nulliparous females (relative risk = 2.5, P = 0.02). There was no statistically significant difference in the incidence of acute GVHD, however, between patients with parous donors and male donors (relative risk = 1.3, P = 0.26). Male patients given grafts from parous donors showed a higher incidence of acute GVHD (63%) than female patients (45%), though this difference was not statistically significant. The 5-year probability of survival was 47% for patients with parous donors, 68% for patients with nulliparous donors and 70% for those with male donors. We confirm that prior donor pregnancy represents an important factor in selecting marrow donors or designing clinical protocols for GVHD prophylaxis.

Acute Disease↗

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Adolescent↗

Predictors of vaccination behavior among persons ages 65 years and older.

We estimated influenza vaccination coverage of 32 percent among persons 65 years of age and older from the 1987 Behavioral Risk Factor Surveillance System survey. Race other than White, obesity, lack of seatbelt use, and current smoking were associated with decreased likelihood of having been vaccinated. Controlling for these factors, the best predictor of having received influenza vaccination was having had a medical checkup within the last year (Odds Ratio = 2.40, 95% confidence interval = 1.84, 3.14).

Aged↗

Racial/ethnic differences in smoking, other risk factors, and low birth weight among low-income pregnant women, 1978-1988.

Because of the adverse effects of low birth weight (LBW) on infant morbidity and mortality, one of the 1990 health objectives for the nation has been to reduce the incidence of LBW to 5% among all live births in the United States. Public health surveillance of cigarette smoking during pregnancy has demonstrated an association between smoking and an increased risk of LBW, defined as birth weight of less than 2,500 g. For the period 1978-1988, information on nearly 248,000 women from CDC's Pregnancy Nutrition Surveillance System showed an LBW rate of 6.9%, a high prevalence of smoking during pregnancy (29.7%); and a strong association between smoking during pregnancy and the likelihood of delivering an LBW infant in all age, racial/ethnic, and prepregnancy weight groups. The risk of LBW was greater for smokers than for nonsmokers (9.9% versus 5.7%), creating an excess LBW risk of 4.2% associated with smoking. Overall, the average birth-weight deficit related to smoking was 178 g. Among both smokers and nonsmokers, black women had a higher percentage of LBW infants than did white women, and the risk of LBW related to smoking was greater among black women. That risk tended to increase with age, especially among women with low pregravid weight. Major reductions in LBW might be achieved if smoking were eliminated among pregnant women.

Adolescent↗

Recognition, incidence, and management of oral graft-versus-host disease.

Acute and chronic graft-versus-host disease (GVHD) are significant complications of allogeneic bone marrow transplantation that occur when immunologically active T-cell lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the marrow donor. Oral GVHD lesions closely resemble those seen with a number of autoimmune connective tissue disease, including lichen planus, systemic sclerosis, lupus erythematosus, and Sjögren's syndrome. Mucosal erythema, atrophy, and ulceration are noted clinically; lichen planus-like lesions are the most distinctive oral lesions. Salivary gland changes include changes in both flow rate and sialochemistry. Oral involvement ranges between 33% and 75% for patients with acute GVHD and upwards of 80% for those with chronic GVHD. Management of oral GVHD lesions depends on successful systemic therapy, although topical steroids can be of help in some instances.

Acute Disease↗

Prevalence of nutrition-related problems among long-term survivors of allogeneic marrow transplantation.

The nutritional status and prevalence of nutrition-related problems in 192 adult and child allogeneic marrow transplant recipients were evaluated 1 year after transplant in a retrospective chart review. Among these patients, 63% exhibited evidence of chronic graft-versus-host disease (GVHD) at the time of nutrition evaluation, including 44% with extensive disease who were receiving immunosuppressive therapy. Oral sensitivity was observed in 23% of all patients reviewed, and frank stomatitis occurred in 8%. The frequency of xerostomia was 18%; anorexia, 8%; reflux symptoms, 7%; diarrhea, 7%; steatorrhea, 5%; dysgeusia, 3%; and limited exercise tolerance because of dyspnea or joint contractures, 4%. Weight loss 3 to 12 months after transplant was experienced by 28%. Nutrition-related problems, changes in anthropometric indexes indicative of suboptimal nutritional status, and inadequate energy intake were observed more frequently in patients with extensive chronic GVHD than in patients without GVHD or in those with limited GVHD. Our findings indicate a high prevalence of nutrition problems among recipients of allogeneic marrow transplantation 1 year after transplant and, further, suggest the need for ongoing, community-based nutrition monitoring after discharge from a transplant center.

Adult↗

Gynecological abnormalities following allogeneic bone marrow transplantation.

Forty-four post-pubertal women were studied 261-4628 days after allogeneic transplantation to determine the nature and degree of gynecological abnormalities following bone marrow transplantation. Evaluations included pelvic examinations, exfoliative cytology, serum gonadotropin levels, direct preparations for micro-organisms, and microbial cultures. Pelvic abnormalities were detected in 35 of 44 (80%) women and resembled atrophic changes known to occur after ovarian failure. Findings included reduced vaginal elasticity and rugal folds, pale tissues, small vaginal, uterine and cervical size, atrophic vulvovaginitis, introital stenosis, and loss of pubic hair. Atrophic abnormalities were noted in 33 of 36 recipients of total body irradiation (TBI) compared to two of eight women not prepared with TBI (p = 0.02). Vasomotor symptoms were reported in 67% of TBI recipients compared to 38% of those not given TBI. Elevated serum gonadotropin levels suggested that TBI had caused the ovarian failure. Recognition of these gynecological abnormalities can lead to earlier hormone replacement, alleviating unnecessary discomfort and improving the well-being of the marrow transplant recipient.

Adolescent↗

Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia.

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.

Adolescent↗