Improved detection of metastatic Ewing's sarcoma with the use of bone marrow scintigraphy.

Prognosis in Ewing's sarcoma is inversely related to the extent of the disease at the time of presentation. The most common sites of metastases are the lungs and skeleton. Bone marrow metastases may be present but clinically silent. We report the use of Technetium (Tc)-99m bone marrow scintigraphy to detect sites of marrow involvement by metastatic Ewing's sarcoma. This method of evaluation allowed identification of sites of involvement by Ewing's sarcoma that were not available by any other method of evaluation. In several instances, information provided by this method was pivotal in the management of these patients. Based on this small series of patients, bone marrow scintigraphy appears to be a sensitive modality in the detection of metastatic disease in patients with Ewing's sarcoma. Better understanding of the role of bone marrow scanning and its correlation with other diagnostic procedures in Ewing's sarcoma will require further study.

Phase I evaluation of beta-2'-deoxythioguanosine in pediatric patients with leukemia.

Thirty-one pediatric patients with acute leukemia who had relapsed on either 6-mercaptopurine or 6-thioguanine were treated with beta-2'-deoxythioguanosine, which was administered as an iv infusion every 12 hours for three or six doses every 2 weeks. Severe nausea and vomiting and urate nephropathy were the dose-limiting toxic effects. Therapeutic responses occurred in four of 24 children with acute lymphocytic leukemia and in two of seven with acute nonlymphoblastic leukemia.

A clinical trial of prostaglandin E2 to increase erythropoiesis in anemia of end stage renal disease. A preliminary report.

Prostaglandin E2 is known to stimulate erythropoiesis by different mechanisms. A clinical trial of prostaglandin E2 to stimulate erythropoiesis in four patients with anemia of end stage renal disease resulted in an increment in peripheral blood Burst Forming Units-Erythroid (BFU-E). This increase in erythroid progenitors returned to baseline with cessation of therapy. A significant increase in serum erythropoietin (EPO) activity was demonstrated in one patient and was noticeable in another. Side effects mainly consisted of local pain at the site of the infusion and vomiting.

The relationship between human spleen and blood erythroid burstforming units (BFU-E).

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.

Triosephosphate isomerase deficiency. A case report with neuropathological findings.

A 12-year-old girl had chronic nonspherocytic hemolytic anemia due to triosephosphate isomerase deficiency. Developmental and motor delay and muscular weakness were followed by cerebellar dysfunction and finally spasticity with hyperreflexia. Abnormal histopathological findings were hyaline cell bodies and axonal "spheroids" in the hypothalamus and cerebellar cortex, severe neuronal loss in the dentate and olivary nuclei, and partial loss of cerebellar Purkinje's and granular layer cells (olivocerebellar atrophy).

Inhibitory effects of interferon on mouse megakaryocytic progenitor cells in culture.

Mouse bone marrow cells were grown in plasma clots, megakaryocyte formation was stimulated with human urinary erythropoietin (Ep). The expression of megakaryocyte colony forming units (CFUM) and of single megakaryocyte forming units (M) was evaluated after seven days in culture. Usually ten times more M than CFUM were found. Megakaryocytic colony formation showed a linear dependence on cell dose from 0.5 to 2 X 10(5) cells/clot. The colony size frequency distribution exhibited a single peak in the two-cell size class, followed by a continuous decrease, suggesting that cell division may occur asynchronously in cells making up a colony. Mouse L cell interferon (IF) in doses from 10 to 1000 U/ml was included in clots together with Ep. This resulted in a biphasic, dose dependent reduction of colony formation and of single megakaryocyte formation. At all doses tested CFUM were more sensitive to IF than M. These observations are best explained by a differential inhibitory effect of IF on replication of two or more classes of megakaryocytic progenitor cells.

Constancy of erythroid burst forming unit (BFUE) levels in the blood of hematologically normal individuals.

Repeated determination of circulating blood BFUE levels in 7 hematologically normal individuals, during a 6 to 16 month period, showed their respective levels to be maintained within narrow limits (coefficient of variation did not exceed 15.1%). However, males differed from each other 3-fold and females as much as 12-fold in the number of BFUE/ml blood. These differences may reflect various sizes of the early erythroid progenitor compartment, which in the presence of different levels of humoral regulators of erythropoiesis are capable of maintaining a normal rate of red cell production. Our findings suggest that the observation of changes of the blood BFUE level of individuals, over a period of time, may be indicative of a change in their erythropoiesis and may shed some light on the physiological role of the peripheral blood BFUE.

Human erythroid burst-promoting activity produced by phytohemagglutinin-stimulated, radioresistant peripheral blood mononuclear cells.

The regulation of erythroid burst-colony formation was studied in cultures of human peripheral blood mononuclear cells. Numbers of erythropoietin-stimulated colonies obtainable from the cells in response to various treatments were compared. One-day preincubation of the cells with phytohemagglutinin (PHA) doubled the yield of colonies. Irradiation of the cells with 3000 rad eliminated their ability to form erythroid bursts, but did not impair the ability of PHA-treated cells to enhance burst formation when added to a fresh batch of cells. This was due to a humoral factor, since media conditioned by PHA-treated washed cells were as effective as the cells themselves. When cells were separated into subpopulations by an adherence procedure and according to their ability to form rosettes with sheep red blood cells, it was found that the PHA-dependent burst-promoting activity released into the medium originated in a nonadherent, nonrosetting (T-cell depleted) cell population.

A fatal case of inappropriate ADH secretion induced by cyclophosphamide therapy.

Cyclophosphamide is used extensively to treat malignancies. A 5-year-old boy with stage IV neuroblastoma is described who developed a fatal syndrome of inappropriate antidiuretic hormone (ADH) secretion after high dose cyclophosphamide therapy.

Iatrogenic TMJ difficulty: cervical traction may be the etiology.

Patients in cervical traction for the treatment of cervical spine syndromes frequently complain that the traction makes them worse. It is possible that such patients may be suffering from TMJ symptoms. The physician treating a patient with cervical traction should consider prescribing an occlusal splint for patients without posterior teeth. The splint should be designed to distribute the stresses through the mandible to the maxillae via the teeth, splint, and TMJ.

Suppressive effect of interferon on erythroid cell proliferation.

The effect of interferon on mouse and human in vitro erythropoiesis was investigated using the mouse marrow CFU-E and the human blood BFU-E systems, respectively. Homologous interferons were found to have a marked inhibitory effect on mouse CFU-E and human BFU-E proliferation. This inhibitory effect was dose related and independent of the erythropoietin concentration used. The effective concentration of human interferon was within the range observed in humans following viral infections. It is suggested that interferon may play a role in the mechanism of the acute erythroblastopenic crisis observed at times in patients with chronic anemia following viral infections.

Suppression of mouse erythroid colony formation by L1210 leukemia cells.

The effect of L1210 transplantable leukemic cells on in vitro formation of erythroid colonies from CD2F1 mouse bone marrow progenitor cells (CFU-E) was investigated. Clonal cell culture was carried out by a methylcellulose technique. Human urinary erythropoietin served as the stimulator. After 44 hours of incubation aggregates of eight or more erythroid cells were scored as colonies. The number of CFU-E which could be demonstrated in marrow cells from mice that had been injected intravenously 6 days before with 5 x 10(4) L1210 cells was far below that obtained from normal marrow cells. When 1.3 x 10(5) marrow cells from leukemic mice or L1210 ascites cells were cultured with an equal amount of normal cells, the number of CFU-E expressed was reduced by 51% and by 86%, respectively, relative to controls with normal cells only. Neither lethally irradiated L1210 cells (4500 rad) nor L1210 cell conditioned media suppressed erythroid colony formation. It is suggested that in L1210 leukemia erythropoiesis is decreased because of a cell-to-cell inhibitory action of the leukemia cells on CFU-E.

Acute myelomonocytic leukemia in children. Possible use of the soft agar culture technique in the differentiation of cellular subtypes.

In 8 children with acute myelomonocytic leukemia (AMML), colony formation in soft agar cultures derived from bone marrow cells was studied in an attempt to differentiate the monocytic (Schilling) from the myelomonocytic (Naegeli) types. The children did not differ markedly in their clinical and morphological parameters. Three in vitro growth patterns were observed: markedly decreased or no growth in 4 cases, extensive growth of granulocytic colonies in 2 cases, and extensive growth of macrophage colonies in the remaining 2. It is suggested that the marrows presenting diminished or no growth patterns are presumably of acute myelogenous leukemia patients with a monocytic component. The excessive granulocytic or macrophage colony growth may be an in vitro indication for an in vivo proliferation of either granulocytic or monocytic leukemic cell lines, and therefore may represent the Naegeli or Schilling variants of AMML respectively. If these observations can be approved in a larger series of AMML patients, this approach can be valuable as another tool in the differential diagnosis of the subtypes of AMML in children.

A beneficial effect of the in situ kidney on in vitro marrow erythropoiesis in chronic renal failure.

The effect of the in situ kidney on transfusion requirements and in vitro erythropoiesis was investigated in 20 patients with end stage renal disease undergoing hemodialysis. 6 of the 12 patients with in situ kidneys did not require transfusion, whereas the other 6 had an average monthly transfusion requirement of 277 ml of sedimented RBCs. All 8 anephric patients required transfusions with an average requirement of 352 ml of sedimented RBCs per month. Serum erythropoietin activity was inappropriately low for the degree of anemia in all but 1 patient, and bone marrow was uniformly hypocellular. Marrow cells from patients with in situ kidneys exhibited a greater response to erythropoietin than marrow cells from their anephric counterparts. The response was not improved by hemodialysis.