Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy.

BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory multiple myeloma. We conducted a phase I/II trial of the combination of lenalidomide and chemotherapy to evaluate the safety and efficacy of the combination. METHODS: The 62 patients enrolled received liposomal doxorubicin 40 mg/m(2) i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days 1-4 (DVd), and lenalidomide on days 1-21 in 28-day cycles. Primary end points were maximum tolerated dose (MTD) of lenalidomide with DVd chemotherapy and overall response rate (ORR) by Southwest Oncology Group criteria of the combination. FINDINGS: The median age was 62 years, 70% of patients were males and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd chemotherapy was 10 mg and the dose-limiting toxicity was non-neutropenic sepsis. After 7.5 months of median follow-up, the ORR of the combination was 75%, with 29% of patients achieving a complete or near complete remission. The median progression-free survival was 12 months, while the median overall survival has not yet been reached. INTERPRETATION: The combination of lenalidomide and DVd chemotherapy was well tolerated and resulted in high response rates in this mostly refractory patient population. Evaluation of this combination in newly diagnosed patients is warranted.

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Dietary intake and health outcomes among young children attending 2 urban day-care centers.

OBJECTIVE: To assess the impact of the Child and Adult Care Food Program (CACFP) on diet and 3 health outcomes--weight-for-height status, dental caries (tooth decay) score, and number of days of illness--among preschool children attending 2 urban day care centers. DESIGN: Dietary intake and health outcome measures were assessed and compared for children attending 2 day-care centers in an urban community. Data were obtained for 14 days of dietary intake, which were analyzed for energy and 15 nutrients and 6 food groups; anthropometric measures, including weight-for-height; dental caries; and days of illness. SUBJECTS/SETTING: Forty 3- to 5-year-old black children from 2 day-care centers participated. One center participates in the CACFP. At the other center, children bring all meals and snacks from home. STATISTICAL ANALYSES PERFORMED: Data from the 2 groups of children were compared using parameteric and nonparametric t tests. RESULTS: Children receiving CACFP meals at day care had significantly higher mean daily intakes of vitamin A (804 +/- 191 vs 595 +/- 268 retinol equivalents), riboflavin (1.45 +/- 0.32 vs 1.21 +/- 0.22 mg), and calcium (714 +/- 180 vs 503 +/- 143 mg) than the children who brought all of their meals and snacks from home. Children who received CACFP meals also consumed significantly more servings of milk (2.9 +/- 0.9 servings vs 1.5 +/- 0.7) and vegetables (1.8 +/- 0.5 vs 1.2 +/- 0.5 servings) and significantly fewer servings of fats/sweets (4.6 +/- 1.3 vs 5.4 +/- 1.1 servings) than children who brought their meals. Weight-for-height status and dental caries scores did not differ between the 2 groups. Children from the center participating in the CACFP have significantly fewer days of illness (median 6.5 vs 10.5 days) than children from the nonparticipating center. APPLICATIONS: Nutritious meals provided by the CACFP can improve diets and may promote health among young, urban children. Registered dietitians can contribute to food assistance programs by intervening to enhance the quality of meals served and by examining the impact of participation on measures of diet quality and diet-related health outcomes.

Dietary calcium intakes of urban children at risk of lead poisoning.

Dietary calcium is well known to decrease gastrointestinal lead absorption and thereby reduce the risk for lead poisoning. Because children in economically deprived urban centers are especially likely to have excessive lead exposure, we surveyed dietary calcium intakes of 314 children from the greater Newark, New Jersey, area. The areas of Newark and adjacent communities studied had been previously identified as containing significant sources of environmental lead by geographic information systems technology. An abbreviated National Cancer Institute Health Habits and History Questionnaire, modified to focus on foods high in calcium, was used to determine dietary calcium. Calcium intakes were then compared to the new Dietary Reference Intake (DRI) guidelines. The respondents were primarily the parents of African-American and Hispanic children ranging in age from 1 to 8 years, with a mean age of 3.5 years. The most recent blood lead concentration was 11.4 +/- 0.8 microg/dL (mean +/- standard error), and 48.6% had concentrations at or above the current guideline of 10 microg/dL. Quintiles of calcium intake were: 221 +/- 13; 488 +/- 9; 720 +/- 6; 885 +/- 6; and 1,389 +/- 49 mg/day. Fifty-five of 175 (31.4%) children aged 1-3 years had calcium intakes below the DRI, as did 82 of 139 (59.0%) children aged 4-8 years. The percentage of mothers reporting lactose intolerance in their children was 2.5%. The observation that the children in the highest quintile easily exceeded the DRIs for calcium suggests that urban parents who include dairy foods in their childrens' meals can provide a diet that meets the DRI guidelines. Children in the lowest quintiles are at risk of increased absorption of the environmental lead to which they are inevitably exposed, as well as other problems associated with a low intake of dietary calcium. The data suggest that both lead exposure and low dietary calcium continue to pose significant health risks to urban minority children.

Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people.

A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.

Dietary lead and calcium: effects on blood pressure and renal neoplasia in Wistar rats.

We examined the potential of increased Ca in the diet to modify the effects of Pb on tissue metal concentrations, blood pressure and the incidence of renal tumours. We randomly assigned 48, 5-wk-old male Wistar rats to one of six treatment groups. They were fed a low (0.2%) or high (4.0%) Ca diet for 31 wk and given 0, 1.0 or 100 micrograms Pb/mL in drinking water. In the low Ca groups, increasing concentrations of Pb produced graded increases in mean blood pressure. Rats receiving 4.0% Ca had higher mean blood pressures than the animals fed the 0.2% Ca diet. The 4.0% Ca diet also caused renal and urinary bladder stones to develop in some rats. The high Ca diet did not prevent dose-dependent increases in tissue Pb accumulation, but it caused significant decreases in kidney Cu, femur Mg and Fe in kidney, liver and testis. Femur Mg and Fe and liver Fe concentrations were lowest in rats receiving 4.0% Ca and 100 micrograms Pb/mL. Precancerous and cancerous renal lesions occurred to the greatest extent in the rats receiving 100 micrograms Pb/mL and the high Ca diet. These results suggest that high dietary Ca does not protect against Pb-induced increases in blood pressure or Pb accumulation in tissues and may often produce nephrocalcinosis. In addition, high dietary Ca in the presence of Pb may increase the incidence of renal tumors.

Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly.

The objective of this study was to determine the effects of a year of Zn supplementation on Zn concentrations in circulating cells and on cellular immune functions in the elderly. Subjects, aged 60-89, were given a placebo, 15 mg Zn, or 100 mg Zn daily for 12 months. All subjects also received a multivitamin/mineral supplement that contained no additional Zn. Blood samples were drawn and immune functions assessed prior to and at 3, 6, 12, and 16 months after beginning Zn supplementation. Subject diets were also assessed at each visit. Dietary folate, pyridoxine, alpha-tocopherol, copper, zinc, and magnesium were consistently below recommended intakes. Although plasma Zn increased significantly in the 100 mg Zn treatment group, concentrations of Zn in erythrocytes, mononuclear cells, polymorphonuclear leukocytes, and platelets were not significantly increased by zinc supplementation. Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn. There was a progressive improvement in delayed dermal hypersensitivity (DDH) and in lymphocyte proliferative responses to two mitogens; this may have been due to one or more components of the multivitamin/mineral supplement administered to all study subjects. The enhancement of DDH was significantly greater in the placebo group than in either zinc treatment group. Thus, zinc had a beneficial effect on one measure of cellular immune function while simultaneously having an adverse effect on another measure of cellular immunity.

Micronutrient status and human immunodeficiency virus (HIV) infection.

This study surveyed serum concentrations of vitamins, electrolytes, and trace elements in subjects seropositive for HIV-1 by ELISA and confirmatory Western blot. Thirty subjects (26 males, 4 females) were recruited at a hospital clinic. Seventeen were classified as having mild or severe ARC (AIDS-related complex), 7 had AIDS, and 6 were asymptomatic. Eight had experienced weight loss of 10 pounds or more in the past 6 months. Most (93%) were anergic to skin test antigens. Percentages of subjects with below normal plasma concentrations include: zinc-30%, calcium-27%, magnesium-30%, carotenes-31%, total choline-50%, and ascorbate-27%. Eighty-seven percent of the subjects had at least one abnormally low value. Percentages with above normal values include: folate-37% and carnitine-37%. Some subjects with above normal values for plasma vitamins reported self-supplementation, usually with large doses. The results suggest that one or more abnormally low concentrations of the plasma micronutrients studied here are likely to be present in the majority of HIV seropositive patients.

Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months.

One hundred and three apparently healthy elderly subjects age 60-89 y were randomly assigned to one of three treatments: placebo, 15 mg zinc/d, or 100 mg Zn/d for 3 mo. Plasma Zn was significantly increased only in the 100 mg Zn group. Zn concentrations in erythrocytes, platelets, mononuclear cells, and polymorphonuclear leukocytes were not significantly increased by any treatment. None of the treatments significantly altered delayed dermal hypersensitivity (DDH) to a panel of seven recall antigens or in vitro lymphocyte proliferative responses (LPR) to mitogens and antigens. Fifteen subjects had initially poor lymphocyte proliferative responses that improved in 14 of these individuals during the study; this was not due to Zn supplementation but might have been caused by one or more components of a vitamin-mineral supplement administered to all study subjects.

Zinc and immunocompetence in the elderly: baseline data on zinc nutriture and immunity in unsupplemented subjects.

Zinc nutriture and immune function were studied in 100 subjects, age 60-89 yr. Mean (+/- SD) zinc concentrations found were 84.8 +/- 15.5 micrograms/dL (13.0 +/- 2.4 microM) for plasma, 1.04 +/- 0.24 micrograms (0.016 +/- 0.004 mumol)/10(9) cells for erythrocytes, 4.06 +/- 1.85 micrograms (0.062 +/- 0.028 mumol)/10(9) cells for mononuclear cells, 3.91 +/- 1.77 micrograms (0.060 +/- 0.027 mumol)/10(9) cells for polymorphonuclear leukocytes, 0.53 +/- 0.39 micrograms (0.0081 +/- 0.0060 mumol)/10(9) cells for platelets, and 222 +/- 101 micrograms (3.39 +/- 1.54 mumol)/g for hair. Zinc ingestion was below the RDA in more than 90% of study subjects. The incidence of anergy to a panel of seven skin test antigens was 41%; responses to these antigens were significantly associated with the plasma zinc concentration. Subjects with depressed lymphocyte responses to mitogens had significantly lower platelet and significantly higher mononuclear cell zinc concentrations than those with normal responses.

Effect of selenium and molybdenum on methylbenzylnitrosamine-induced esophageal lesions and tissue trace metals in the rat.

Thirty-six weanling male Sprague-Dawley rats were randomly assigned to one of four treatment groups: SE rats received 4.0 ppm selenium as sodium selenite in drinking water containing 1% sucrose; 15MO rats received 15 ppm molybdenum as sodium molybdate in the drinking water; 45MO rats received 45 ppm molybdenum in their water; and CON rats received distilled-deionized water containing only 1% sucrose. The esophageal carcinogen methylbenzylnitrosamine (MBN) was administered intragastrically in 10% ethanol twice per week for 5 wk at a dose of 2.5 mg/kg. MBN dosing was followed by a 12-wk period for tumor promotion. After this, heart, lungs, liver, spleen, kidneys, testes, tibia, muscle, brain and esophagus were excised. The esophagus was examined for MBN-induced lesions using dissecting and light microscopes and a portion was analyzed for Se. All other tissues were analyzed for Cu, Zn, Fe and Mn; some were also analyzed for Se and Mo. Most rats had precancerous lesions, and all rats had papillomas. There were no significant differences among the four treatment groups in the incidence and number per rat of precancerous lesions or gross papillomas. The SE group had significantly fewer carcinomas per rat than the other groups. The SE rats exhibited a number of significant differences in tissue trace element concentrations; in particular, they had higher Fe concentrations in heart, kidney and spleen than the other rats. The SE rats also had significantly greater urinary excretion of Mn and Fe, and excretion of the latter elements was significantly correlated with that of selenium.(ABSTRACT TRUNCATED AT 250 WORDS)