Alfred A. Rimm

Bone Marrow Transplantation for Chronic Myelogenous Leukemia in Chronic Phase: Increased Risk for Relapse Associated with T-Cell Depletion

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.

Hospital Characteristics and Mortality Rates

The Health Care Financing Administration (HCFA) publishes hospital mortality rates each year. We undertook a study to identify characteristics of hospitals associated with variations in these rates. To do so, we obtained data on 3100 hospitals from the 1986 HCFA mortality study and the American Hospital Associations 1986 annual survey of hospitals. The mortality rates were adjusted for each hospitals case mix and other characteristics of its patients. The mortality rate for all hospitalizations was 116 per 1000 patients. Adjusted mortality rates were significantly higher for for-profit hospitals (121 per 1000) and public hospitals (120 per 1000) than for private not-for-profit hospitals (114 per 1000; P less than 0.0001 for both comparisons). Osteopathic hospitals also had an adjusted mortality rate that was significantly higher than average (129 per 1000; P less than 0.0001). Private teaching hospitals had a significantly lower adjusted mortality rate (108 per 1000) than private nonteaching hospitals (116 per 1000; P less than 0.0001). Adjusted mortality rates were also compared for hospitals in the upper and lower fourths of the sample in terms of certain hospital characteristics. The mortality rates were 112 and 121 per 1000 for the hospitals in the upper and lower fourths, respectively, in terms of the percentage of physicians who were board-certified specialists (P less than 0.0001), 112 and 120 per 1000 for occupancy rate (P less than 0.0001), 113 and 120 per 1000 for payroll expenses per hospital bed (P less than 0.0001), and 113 and 119 per 1000 for the percentage of nurses who were registered (P less than 0.0001).

Risk factors for acute graft‐versus‐host disease

Summary. Acute graft‐versus‐host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA‐identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2‐year actuarial probability was 54% (95% confidence interval 52–56%) for absent or mild and 46% (44–48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex‐match (female→male greater than others, relative risk 2.0, P<0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P<0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P<0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female→male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P<0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

Relationship of obesity to diabetes: Influence of obesity level and body fat distribution

The relationship of clinical diabetes to body fat distribution and obesity level was examined in 15,532 women. After adjusting for relative weight, all upper body segment girth measurements (neck, bust, and waist) had strong positive associations with diabetes. In contrast, the lower body segment girth measurement (hips) had an equally strong but inverse association with diabetes. Based upon waist-to-hip girth ratio, women were divided into four subgroups. The prevalence of diabetes increased with increasing values of this ratio. Women in the upper quartile had about three times the prevalence of diabetes as women of comparable obesity level in the lowest quartile. Women with both upper body fat predominance and severe obesity had a relative risk of diabetes 10.3 times as great as nonobese subjects with lower body fat predominance. The results suggest that localization of fat in the upper body segment and severe obesity are two distinct additive risks for diabetes.

Hip fracture incidence among the old and very old: a population-based study of 745,435 cases.

Data were obtained from the Health Care Financing Administration and the Department of Veterans Affairs (formerly called Veterans Administration) on all hospital discharges among the elderly population from 1984 through 1987 and combined with census estimates to calculate incidence rates of hip fracture for the elderly population of the United States. Rates for White women were the highest, reaching 35.4 per 1,000 per year among 95 year-olds. Comparably, White men, Black women, and Black men experienced similar age-related increases in risk, although of less magnitude and relatively less rate of change, respectively.

ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKAEMIA

In 117 patients with chronic myelogenous leukaemia (CML) treatment with a combination of high-dose chemoradiotherapy plus transplantation of allogeneic bone-marrow from HLA-identical, mixed-lymphocyte-culture-identical siblings resulted in an actuarial probability of 3-year survival of 63 +/- 16% (95% confidence interval) for 39 patients transplanted in chronic phases; 36 +/- 14% for 56 transplanted in accelerated phase; and 12 +/- 15% for 22 transplanted during blast crisis. Irrespective of disease status at the time of transplantation, and in contrast to chemotherapy, a plateau-effect was observed in the survival curves starting 14 to 19 months after transplantation. The actuarial probability of recurrent or persistent leukaemia at 3 years was 7 +/- 9% for patients transplanted in chronic phase, 41 +/- 19% for accelerated phase, and 41 +/- 39% for blastic phase. All relapses occurred within 18 months of transplantation. This study demonstrates that long-term disease-free survival in CML can be achieved with bone-marrow transplantation. Best results were obtained in patients transplanted during chronic phase of the disease.

The association of obesity with joint pain and osteoarthritis in the HANES data

Data from 4225 persons from the National Health and Nutrition Examination Survey (HANES) was used to determine whether obesity was associated with osteoarthritis (OA) or joint pain. Subjects were divided into four groups on the basis of sex and race. We found that obesity was associated with OA of the knee for each sex/race group (p less than 0.01). The association was strongest for women, and it was present even for subjects without evidence of knee pain on physical examination. Frame size was not significantly associated with OA of the knee. Relative weight was weakly associated with OA of the hips in white women and nonwhite men but not significantly associated with OA of the sacroiliac joint. Diabetes did not seem to be an important risk factor for OA. These results suggest that the additional mechanical stress resulting from obesity is the principal reason for the association between obesity and OA.

Body fat distribution, plasma lipids, and lipoproteins.

The relation of body fat distribution as measured by the ratio of waist to hip circumferences (WHR) to plasma levels of lipids and lipoproteins was studied In 713 men and 520 women who were employed by two Milwaukee companies. Quetelet Index (kg/m2), waist girth, hip girth, and WHR were each positively related to levels of total cholesterol, trlglycerldes, apollpoproteln B, and the ratio of total to high density llpoproteln (HDL) cholesterol. In addition, the anthropometrlc measures were Inversely associated with levels of HDL cholesterol. (Controlling for age, alcohol intake, exercise level, current smoking status, and oral contraceptive use only slightly reduced the strength of the correlations.) In addition, WHR and Quetelet Index were Independently related to llpld and llpoproteln levels, and the magnitudes of the associations were roughly equivalent For example, the mean (covarlate-adjusted) trlglycerlde level among men In the upper tortile of the Quetelet Index was 37 mg/dl higher than for men in the lower tertlle of the Quetelet Index; the corresponding difference according to WHR tertlles (upper to lower) was 39 mg/dl (p<0.01 for both effects). These findings Indicate that In healthy men and women a less favorable lipid and llpoproteln profile Is associated with elevated levels of both Quetelet Index and WHR.

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

OBJECTIVE To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. DESIGN Retrospective comparison of two cohorts of patients. SETTING Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. PATIENTS Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. MAIN RESULTS Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. CONCLUSIONS These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.

The association of body weight with recurrent cancer of the breast

Recurrence of carcinoma of the breast after radical mastectomy was associated with preoperative body weight among patients observed for up to 24 years. Patients who had no axillary lymph node metastases and who weighed 130 pounds or less had an accumulative recurrence free survival superior to that of heavier patients. The advantage was unassociated with significant differences in menopausal status, clinical stage, or tumor size. High fat diet and large body mass have been linked epidemiologically with high risk for breast cancer; whatever biologic mechanisms are involved may also promote growth of residual tumor after potentially curative surgery. Diet and weight reduction may represent empirical means for improving the prognosis of heavy individuals with early stages of breast cancer.