Search

We would like to offer several comments about the article by Wishingrad and Elegant concerning replacement transfusions (Pediatrics, 28:331, 1961). The authors consider a positive Coombs test sufficient indication for an exchange transfusion in an erythroblastotic infant born into a family in which previously affected siblings have required exchange transfusions. A positive Coombs test does not of itself serve as adequate indication for an exchange transfusion. There must exist the same criteria for an exchange transfusion in any affected patient, particularly when one considers the fact that this procedure is not totally benign.

The role of eosinophiles in hematopoiesis is not clear. Despite the presence of eosinophilia in a variety of parasitic and other conditions, the leukocyte counts frequently are not elevated. This suggests a possible inhibitory effect of eosinophiles on granulopoiesis. This study was undertaken to examine the effects of eosinophiles on granulocytic colony forming units in culture (CFU-C) of mice bone marrow (BM). Marrow of normal as well as eosinophilic inbread C-57 black mice infected with Trichinella spiralis was cultured in semi-solid media with 1) anti-eosinophilic sera produced against mice eosinophiles in rabbit (AES), 2) the addition of purified eosinophiles, 3) colony stimulating activity (CSA), 4) α-culture media, 5) normal rabbit serum, 6) eosinophilia extracts, and 7) irradiated eosinophiles. Each of the above experiments was repeated with and without added CSA. Addition of AES to BM cultures containing CSA sharply increased CFU-C levels in eosinophilic mice compared to CSA and rabbit serum (controls) alone (P

American Burkitt's lymphoma has been identified as a monoclonal IgM (Kappa or Lamba chain) lymphoprolipherative disorder. The nature of immunoglobulin synthesis in culture of tumor derived from 3 such patients (ages 5, 6, and 15 years) was investigated. Tissue with cytologic and morophilogic Burkitt's criteria included mediastinal node, abdominal node and marrow. Cells were cultured as 1 × 106 cells/ml in leucine-difficient Eagle's media containing 10% fetal calf serum and 5 uC 3H-leucine in 5% CO2 at 37°C for 72 hours. Ig's were measured by solid phase radioimmunoassay. Specific anti-Fab and anti-IgG, M, and A, following elution from insoluable immunoabsorhants, were convalently linked to bromacetyl cellulose (BAC) and specificity was established on acrylamide gels. Synthesis was determined as degradation (DPM)/106 cells: total protein - 1800 (640-2570), Ig-120 (20-280). Molecular weight of the Ig was consistant with IgM and verified with BAC-anti-IgM. Neither IgG nor IgA were synthesized. The % of newly synthesized protein as IgM ranged from 2.5-12.5%. Total protein (TP) and total Ig synthesized from normal lymphocytes in culture averaged 3100 and 290 DPM/106 cells, respectively (%TP as Ig-9%: IgG-5.5%. IgM-3%. IgA-1.5%). With this method, Ig quantitation clearly identified IgM as the sole Ig synthesized by this tumor. The patients were treated alike (prednisone, cyclophosphamide and vincristine initially). The longest survival to date has occurred in the patient with the highest level of IgM synthesis.

The extent of leukemic marrow (BM) involvement in children with ALL is often unrelated to the degree of anemia. This serial study was carried out to correlate marrow CFU-E with stages of disease. BMs from 35 normal children served as controls. In 29 ALL patients 64 cultures were done; 14 newly diagnosed and untreated; 32 in remission; 18 in relapse. BM cells were cultured with and without erythropoletin (EPO) and included EPO dose response curve. CFU-E at diagnosis was significantly lower than controls, and despite complete remission, values did not reach the normal range. The mean value of cultures obtained during remission (166 ± 47 S.E./106 nucleated cells) was markedly higher than the newly diagnosed (17 ± 8 S.E.) or relapse patients (25 ± 13 S.E., p

Leukocytosis with predominance of polymorphonuclear leukocytes occurs in a variety of primary or metastatic hepatic tumors without apparent explanation. A 17-year-old male with lymphoepithelioma developed marked leukocytosis following the onset of liver metastases. In order to gain insight into the origin of the leukocytosis, granulopoietic colony stimulating activity (CSA) of patient's plasma and leukocytes were examined and compared to control. Leukocyte conditioned media (LCM) was prepared by the double layer culture method. The assay consisted of non-adherent marrow cells from normal individuals cultured in methylcellulose, fetal calf serum and α-media. With the various CSA sources in this system, the number of granulocytic colony forming units (CFU-C) is proportional to the amount of CSA present and therefore allows for quantitative comparisons. The number of CFU-C produced with the patient's plasma was significantly higher (P

ENHANCING EFFECT OF RABBIT ANTI-MOUSE EOSINOPHIUC SERUM (AES) ON GRANULOPOIETIC COLONY FORMING UNITS IN CULTURE (CFU-C)

Quantitaticn of peripheral blood lymphocyte immunoglobulin biosynthesis was evaluated as a method for detection of humoral immunodeficiency. Lymphocytes isolated from 3-15 cc of heparinized blood, using Ficoll-Hypaque gradients, were incubated in leucine free medium (1×106 cells/cc) with tritiated leucine for 48 and 72 hrs. Newly synthesized secreted IgG and total immunoalobulins were measured using specific anti-immunoglobulin antibodies coupled to insoluble bromacetylcellulose. Synthesis was readily detected in newborn infants as young as 28 wks gestation. The normal range (6 individuals) for total immunoglobulin synthesis and IgG synthesis was 1.3-5.5%, and 0.3-1.6%, respectively, of total secreted proteins. The lymphocytes of a patient with X-linked agammaglobulinemia synthesized no immunoglobulins. In a patient with non-X-linked agammaglobulinemia (with B-cells), total immunoglobulin and IgG synthesis was 0.20% and 0.13%, respectively. A patient with common variable hypogammaglobulinemia (normal IgM, low IgG, absent IgA) also showed depressed synthesis (total immunoglobulins 0.70%, IgG 0.40%). Quantitation of lymphocyte immunoglobulin biosynthesis appears to be a useful technique for the early diagnosis of humoral immunodeficiency and may be of potential value for the detection of immunodeficiency disease carriers.

Agranulocytosis with eoisnophilia is known to occur. We examined the in vitro effects of AES on bone marrow (BM) cultures of 2 patients with eosinophilia (immune deficiency, Felty's syndrome - 35% and 60% eosinophilia, respectively) in combination with neutropenia. BM's were cultured in a methyl cellulose system using combinations of human colony stimulating activity (CSA), normal rabbit serum (RS), patient's sera (PS), AES, and α-media (α). Following are the results reported as CFU-C/105 Cells. The results indicate that the addition of AES to CSA enhances the colony forming ability of eosinophilic patients but has no effect on normal controls. In another experiment, the addition of AES to non-adherant marrow cells (lacking CSA) failed to produce colonies, indicating the CSA requirements for the AES “enhancing” effect. The significant increase in CFU-C, promoted by AES, in BM cultures of these patients supports the likelihood of an eosinophile-inhibiting effect on neutrophile production. This suggests a role for eosinophiles in maintaining granulopoietic homeostasis.

668 RECURRENCE OF PNEUMOCYSTIS CARINII PNEUMONIA IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

New treatments are urgently needed for stage IV NB, which becomes resistant to chemotherapy (CT) in 75% of cases. We have treated 6 children (ch) with refractory NB with HD L-PAM, either 120 mg/m2 (4 ch) or 180 mg/m2 (2 ch), in 3 divided doses, followed by reinfusion of bone marrow (BM) previously frozen in liquid N2 during BM remission. The ch were isolated during the neutropenic phase and supported with red cells and platelets, and hyperalimentation via Broviac catheters. Toxicity: all 6 recovered hemopoietic function, in median periods of 28 days (neutrophils 500), 34 days (retics 1%), and 35 days (platelets 50,000). Gastrointestinal side effects were severe but short-lived. 1 ch developed hepatic venocclusive disease, which regressed completely with supportive measures. 3 ch developed sepsis while neutropenic. 1 ch died after 3 mo complete response (CR) from complications of prior abdominal surgery and had no tumor at autopsy. Responses: 120 mg/m2 (4 ch)--1 CR (6 mo), 1 PR (1 mo), 2 NR. 180 mg/m2 (2 ch)--2 CR (3 mo and 4+ mo). Conclusions: 1. HD L-PAM is clearly active against NB. 2. Autologous BM reinfusions protect against severe myelosuppression. 3. BM autografting may uncover other dose-limiting toxicities of L-PAM. 4. L-PAM should be combined with other agents in further phase II and III studies.

In 1953, Weiner et al1published the first well documented case of a specific auto-immune hemolytic anemia, an adult from whose serum and red cell eluate antibodies with anti-e specificity were isolated. Subsequently, additional reports of specific auto-antibodies appeared in the literature and with rare exception were shown to be part of the Rh system.2-4Reference to the majority of these cases has been cited by Dacie,5who noted that the incidence of specific auto-antibodies approximated 30%, with anti-e being the most common. However, prior to 1961, no reports of specificity had been described among the 30 carefully reviewed cases in infants under 1½ years of age.6-8Shortly thereafter, the first such examples were reported by Laski and co-workers,9who described a 5½-month-old infant with anti-E and anti-f and a 2½-month-old infant with anti-D antibodies. The present report is a description of anti-D specificity in