Implications of the anemia of chronic disorders in patients anticipating radiotherapy.

The authors assess prevalence of anemia in a population of patients anticipating radiation therapy. They also characterize the anemia and determine its relationship to stage, inflammation, and mortality. Blood counts were recorded for 81 of 103 patients surveyed during August 1988.

Paraneoplastic erythrocytosis in a young adult with an erythropoietin-producing Wilms' tumor.

Paraneoplastic erythrocytosis in patients with Wilms' tumors is exceedingly rare, with only three reported cases in the literature. We report a case of a young man with Wilms' tumor with a significant erythrocytosis but a normal serum erythropoietin level and a tumor that elaborated erythropoietin.

Suppressive effects of pentoxifylline on natural killer cell activity.

The methylxanthine derivative pentoxifylline, widely used as a hemorrheologic agent in the treatment of peripheral vascular disease, is now being evaluated for potential applications in patients with cancer. Recent studies have shown that pentoxifylline can modulate a number of neutrophil functions at in vitro concentrations of at least 50 micrograms/ml. Using a standard51chromium-release assay, we studied the suppressive effects of pentoxifylline on natural killer (NK) cell activity and found that pentoxifylline, at concentrations of 50 and 100 micrograms/ml, suppressed the in vitro NK cell activity of healthy volunteers by 25% and 75%, respectively.

Effect of recombinant human erythropoietin on renal function in humans.

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.

The safety and the efficacy of maintenance therapy of recombinant human erythropoietin in patients with renal insufficiency.

Ten anemic predialysis renal patients participated in a study to examine the long-term effects of recombinant human erythropoietin (r-HuEPO) treatment. The drug was initially given intravenously three times a week for 1 to 5 months, then by subcutaneous injections three times each week for 4 to 8 months, and finally by subcutaneous injection once weekly for 3 to 18 months. The duration of follow-up ranged from 11 to 29 months.

Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial.

Study Objective: To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients.

Design: Randomized, double-blind, placebo-controlled trial for 8 weeks.

Setting: Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital.

Differential elaboration of prostaglandin E2 by cells of the hemopoietic microenvironment in response to endotoxin.

Eight daily intraperitoneal injections of endotoxin (LPS) induced hematologic abnormalities in mice like those previously observed with chronic inflammation, sterile abscess, and tumor bearing. By the ninth day, anemia, leukocytosis, hypocellularity of the bone marrow, and compensatory hemopoietic hyperplasia of the spleen had occurred. The suppressed hemopoietic recovery and impaired survival of mice with these abnormalities, after receiving an ordinarily sublethal dose of total body irradiation (600 cGy T.

Chronic inflammation impairs hematopoiesis and survival after irradiation.

Our studies show that the induction of a chronic inflammatory lesion in the left hind legs of mice by administration of 5000 rad produced distinct abnormalities of the hematopoietic system. A peripheral neutrophilia accompanied reduced numbers of total nucleated cells, stem cells, stromal cells, erythroblasts, and lymphocytes in the unirradiated femoral marrow, and the spleen was enlarged. Mice with these hematopoietic abnormalities promptly succumbed with bone marrow failure to a sublethal dose of total body irradiation (600 rad TB).

Tumor bearing impairs hemopoietic recovery and survival after irradiation.

These investigations were undertaken to determine whether the hemopoietic abnormalities induced by bearing a solid sarcoma-180 (S-180) impaired recovery of hemopoiesis and shortened survival of mice after sublethal total body irradiation. Mice, intramuscularly injected with 4 x 10(6) S-180 cells before or after 600 or 700 rad total body (TB) irradiation were followed for over 1 month postirradiation compared to irradiated control mice or to tumor bearing mice receiving no irradiation. Whereas more than half of the control mice survived doses of 600 to 700 rad TB, none of the tumor bearing mice survived the same dose for over 3 weeks.

Residual injury to the hemopoietic microenvironment following sequential radiation and busulfan.

Our earlier studies in mice showed that sequential radiation and cyclophosphamide suppressed marrow stromal cells (MSC) and prevented local hemopoietic repopulation for several months. Because others have shown that busulfan administration caused marrow aplasia, we studied its ability, combined with radiation, to produce a persistent microenvironmental defect in mice. Intraperitoneal administration of four weekly doses of 20 mg/kg busulfan, starting one week after 1500 rad leg irradiation, produced a severe microenvironmental lesion for 6 months reflected by lack of repopulation in femoral marrow to greater than 50% of normal by MSC, hemopoietic stem cells (CFU-S), and granulocyte-macrophage precursors.

Prostaglandin E and the erythropoietic and stromal insufficiency induced by extramedullary tumor.

This paper reports the results of our studies concerning the specificity and mechanism of anemia in tumor-bearing mice. Three different types of transplanted extramedullary tumors, including a carcinoma (EAC), a sarcoma (S-180), and a leukemia (L-1210) produced anemia, neutrophilia, and medullary erythroblastopenia. Because the most striking effects were observed with S-180, it was selected for detailed study.

Tumor-induced suppression of marrow stromal colonies.

The studies reported in this paper evaluated one of the mechanisms by which extramedullary tumor caused anemia, neutrophilia, medullary erythroblastopenia, and suppression of marrow stromal cells (MSC) in tumor bearing mice. Since MSC have been shown to support hemopoiesis, we asked whether tumor released a suppressor which directly inhibited MSC colonies, and if it did, whether or not it was prostaglandin-E (PGE). We found that co-culture of Ehrlich ascites carcinoma (EAC) and Sarcoma (S-180) cells with normal mouse bone marrow cells profoundly suppressed formation of MSC colonies.

Prostaglandin-mediated enhancement of erythroid colonies by marrow stromal cells (MSC).

Marrow stromal cells (MSC) released a diffusible substance in split-phase culture that enhanced the response of erythroid colonies to erythropoietin when MSC were present in small numbers and suppressed when they were present in large numbers. Incremental concentrations of indomethacin inhibited the enhancement, but it did not suppress growth of MSC colonies. Radioimmunoassay of conditioned media demonstrated that MSC produced E-type prostaglandin (PGE) that was inhibited by non-lethal concentrations of indomethacin sufficient to suppress MSC enhancement of erythroid colonies.

Characterization of marrow stromal (fibroblastoid) cells and their association with erythropoiesis.

Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, CFUE, and CFUC in co-culture with MSC, and the in vitro characteristics of MSC. One month after 5000 rad LI, erythroblasts and MSC fell to 18% and 26% respectively.

Remission of giant lymph node hyperplasia with anemia after radiotherapy.

We have described a 51-year-old patient with unresectable mesenteric giant lymph node hyperplasia of the plasma cell type, severe systemic manifestations, and profound anemia. Supression of erythropoiesis may have been related to the presence of a circulating erythropoietic inhibitor produced by the lymphoid tumor. Markedly elevated titers to Epstein-Barr virus capsid antigen suggest that this virus may be important in the etiology of the abnormal lymphoid proliferation.

Suppressive effects of an extramedullary tumor on bone marrow erythropoiesis and stroma.

Mice, bearing a solid extramedullary Ehrlich ascites tumor developed anemia, reticulocytosis, and leukocytosis after 3 weeks of tumor growth. Erythopoiesis in the marrow, as measured by erythroblast counts and radioiron uptake of the humerus and femur, was suppressed to less than 30% of normal. However, striking erythroblastic and granulocytic hyperplasia in the spleen occurred to compensate for suppression of erythropoiesis in the marrow.