Comparison of two doses of intravenous immunoglobulin after allogeneic bone marrow transplants.

Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease. However, the minimum dose required for protection is unknown. This may have significant economic implications. A multicenter randomized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients. Either 250 mg/kg or 500 mg/kg was given weekly from day -8 to day +111. Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival, systemic infection, and acute graft-versus-host disease. The two-dose cohorts had similar event-free survival and infection frequencies. The higher dose was associated with less acute graft-versus-host disease (P = 0.03).

Prevention of graft-versus-host disease by induction of immune tolerance with ultraviolet B-irradiated leukocytes in H-2 disparate bone marrow donor.

Transfusions (Tx) of Ultraviolet B (UVB)-irradiated peripheral blood mononuclear leukocytes (MNL) have been shown to induce humoral immune tolerance to major histocompatability complex (MHC) antigens (Blood 88:4375, 1996). To determine whether cellular immune tolerance to MHC antigens can be induced by the same approach, transplantation of bone marrow and spleen cells from tolerant donors across the H-2 barrier was conducted to study its effect on prevention of graft-versus-host disease (GVHD). After immune tolerance induction by four weekly Tx of UVB-irradiated BALB/c (H-2(d)) peripheral blood MNL into CBA/HT6 (H-2(k)) mice, bone marrow cells (BMC) and spleen MNL from tolerant or naive CBA mice were transplanted into lethally irradiated BALB/c mice. The transplanted mice were followed by measuring body weight, peripheral leukocyte counts, GVHD, survival, and cytokine response. All BALB/c recipient mice were fully engrafted with H-2(k) CBA donor cells after transplantation. The severity of GVHD was significantly attenuated in BALB/c mice transplanted with BMC and spleen MNL from tolerant CBA donor mice. The recovery of peripheral leukocyte and lymphocyte counts were faster and more complete in mice transplanted with cells from the tolerant donors. The serum cytokine profile after transplantation with tolerant donor cells showed increased interleukin-4 and reduced gamma interferon that are consistent with a polarized Th2 response. The results pooled from three separate experiments showed that BALB/c mice transplanted with 5 x 10(6) BMC and 4 x 10(5) spleen MNL from tolerant CBA donors had better overall survival than the control group (72% v 17%, P =.018). The findings show that transplantation with bone marrow and spleen cells from tolerant H-2 disparate donor mice is associated with significant attenuation of GVHD and better outcomes. The results also support that transfusions of UVB-irradiated leukocytes may induce cellular immune tolerance.

Role of class-II major histocompatibility complex (MHC)-antigen-positive donor leukocytes in transfusion-induced alloimmunization to donor class-I MHC antigens.

It has been shown that peripheral-blood mononuclear leukocytes (MNL) are responsible for transfusion-induced alloimmunization to donor major histocompatability complex (MHC) antigens. However, it is not known which subset of MNL is responsible for this immune response. Because elimination of class-II MHC antigen-positive passenger leukocytes effectively prolongs the survival of allografts, it has been hypothesized that class-II positive MNL are responsible for immunizing transfusion recipients to donor MHC antigens. To test this hypothesis, two different approaches were used. First, we compared the alloantigenicity of BALB/c mice (H-2(d)) peripheral blood MNL before and after depletion of class-II positive cells. CBA mice (H-2(k)) were used as transfusion recipients. Antibody development to donor class-I H-2 antigens was determined by flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of MNL depleted for class-II positive cells, only 25% of recipient mice developed antibodies to donor H-2(d) antigens. In contrast, all mice transfused with control MNL became immunized. Second, we studied the alloantigenicity of peripheral MNL from C57BL/6 mice (H-2(b)) with homozygous deficiency of class-II MHC molecules in H-2 disparate recipient mice. After transfusions with class-II MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient mice developed antibodies to donor H-2(b) antigen. All control recipient mice were immunized. The antibody activities of the controls were also higher than those in the treatment group who became immunized. Thus, our study shows that class-II MHC antigen-positive MNL play a significant role in transfusion-induced alloimmunization to donor class-I MHC antigens. The results also support the hypothesis that direct antigen presentation by donor class-II positive MNL to the immune system of transfusion recipients is critical for the initiation of humoral immune response to donor MHC antigens.

Neonatal alloimmune thrombocytopenia associated with maternal anti-HLA antibody: a case report.

PURPOSE: Although neonatal alloimmune thrombocytopenia (NAIT) due to maternal sensitization to human platelet antigens is well described, the role of maternal anti-human lymphocyte antigen (HLA) antibodies in NAIT is not yet firmly established. PATIENT: A 31-week-old girl born prematurely to a G2POA1 mother was noted to have thrombocytopenia which lasted 18 days without any evidence of infection. MATERIALS AND METHODS: Platelet-associated IgG, anti-platelet antibody, and platelet PL(A1) antigen typing were determined using a commercial solid-phase red cell adherent test. Antibodies to platelet glycoproteins human platelet antigen (HPA) 1 to 5 were determined using a commercial ELISA. Anti-HLA antibodies were assayed using a standard lymphocytotoxicity test. Activities and IgG subclass of anti-HLA antibodies in plasma of the mother and other postpartum mothers were measured using purified HLA antigens in an enzyme linked immunoassay. RESULTS: Both mother and infant were positive for HPA-1 (PL(A1)) antigens. The mother's HLA phenotype was A3, A31, B7, B27. The level of platelet-associated IgG was not increased on maternal platelets; however, increased platelet-associated IgG was detected on the infant's platelets. Antibodies to platelet glycoproteins HPA1 to 5 were not detectable in the maternal plasma. Maternal serum was positive for anti-HLA antibodies, which reacted to 23 of 27 panel cells. The presence of HLA antibodies was confirmed by enzyme-linked immunoassay. Of note, the maternal antibodies reacted positively to the infant's platelets and anti-IgG anti-HLA antibodies were detected in the serum sample from the infant collected at birth. When the activity and IgG subclass of the maternal anti-HLA antibodies were compared with those of other mothers known to have high anti-HLA antibody activity, no differences were noted. CONCLUSION: This report documents a patient with neonatal thrombocytopenia induced by maternal IgG anti-HLA antibody. Neither activity nor IgG subclass could explain the occurrence of NAIT. The factors that contribute to NAIT induced by maternal anti-HLA antibodies remain to be identified.

Preoperative chemotherapy for congenital hemangiopericytoma and a review of the literature.

PURPOSE: Malignant hemangiopericytoma is an uncommon tumor in the pediatric age group. A case of congenital hemangiopericytoma is presented with a review of the literature. PATIENTS AND METHODS: A 2-month-old boy presented at birth with an enlarging posterior neck mass. Subsequent histopathologic studies showed findings consistent with hemangiopericytoma. Imaging studies demonstrated an extensive, infiltrative, vascular lesion not readily amenable to surgical resection. A pulmonary metastatic lesion was present. RESULTS: Combined treatment using vincristine, doxorubicin, and cyclophosphamide given preoperatively resulted in a significant decrease in size of the primary tumor, allowing for resection without complication and resolution of the metastatic lesion. CONCLUSION: Preoperative chemotherapy may have a significant role in the management of infants with malignant hemangiopericytoma.

Determination of the rate of reduction in platelet counts in recipients of hematopoietic stem and progenitor cell transplant: clinical implications for platelet transfusion therapy.

BACKGROUND: To investigate how a delay between pretransfusion platelet count measurement and actual platelet transfusion affects the assessment of platelet transfusion responses, the rate of reduction in platelet counts was determined in 30 patients with relatively uncomplicated thrombocytopenia. STUDY DESIGN AND METHODS: Fifteen adult and 15 pediatric patients admitted for hematopoietic stem and progenitor cell transplantation were studied. Platelet counts before and after myeloablative conditioning and after prophylactic platelet transfusions were determined and studied as a function of time. The rates of reduction in platelet counts were determined by linear regression analysis. RESULTS: Platelet counts were reduced at linear rates after myeloablative conditioning or prophylactic platelet transfusion in all 30 patients. The average rates of reduction in platelet counts after myeloablation were 1261 +/- 583 and 1070 +/- 492 platelets per microL per hour (mean +/- SD) for adult and pediatric patients, respectively. The average rate of reduction after platelet transfusions during the thrombocytopenic phase was 740 +/- 280 and 820 +/- 288 platelets per microL per hour (mean +/- SD) for adult and pediatric patients, respectively. The rates of reduction in platelet counts between the two phases were significantly different in the two age groups (adult, p < 0.0001; pediatric, p < 0.015) and were proportionally correlated with initial platelet counts immediately before myeloablation and after prophylactic platelet transfusions. CONCLUSION: The rate of reduction in platelet count can have a significant impact on the evaluation of platelet transfusion responses when there is a delay between pretransfusion measurement of platelet count and the initiation of platelet transfusion. In addition, the rate of platelet reduction determined from this study can be used to confirm an accelerated rate of platelet consumption in thrombocytopenic patients.

Countering rumors about contraceptives.

PIP: Rumors are among the serious problems of the National Population Program today. The principles related to the origin of rumors, who starts rumors pertaining to family planning, and how they spread are outlined. The basic approach in countering rumors for the pill and IUD is diagrammed so that each potential rumor is countered by a medical or nonmedical/technical explanation. Strategies used by information-education-communication programs to prevent rumors such as the small group discussion, selection and training of motivators, and use of mass media are discussed. Rumors about family planning are counteracted not with the use of elaborate techniques but with clear and fairly simple reassurances supported by medical evidence and case histories.^ieng

Getting to know your audience.

PIP: The Population Center Foundation of the Philippines conducted a Study of the Flow of Scientific Information in the Philippine Population Program. It is hoped that the study will provide policymakers and communicators with information helpful in designing improved communication programs within population programs. Phase I of the study included: 1) an analysis of the information flow to and within major family planning agencies; 2) an analysis of family planning newsletter mailing lists; 3) a content analysis of 6 family planning newsletters; and 4) an investigation into the ways scientific/technical information is used by clinic personnel. The study showed that very little scientific information flows from family planning researchers to family planning communicators. Family planning newsletters contain little scientific information and the publications are not shared within organizations. The study pointed out the need for closer links between research institutions and family planning field personnel. A set of guidelines was drawn up for management action to increase the utilization of research by field workers.^ieng

A model for culturally adapting a learning system.

PIP: The Cross-Cultural Adaption Model (XCAM) is designed to help identify cultural values contained in the text, narration, or visual components of a learning instrument and enables the adapter to evaluate his adapted model so that he can modify or revise it, and allows him to assess the modified version by actually measuring the amount of cultural conflict still present in it. Such a model would permit world-wide adaption of learning materials in population regulation. A random sample of the target group is selected. The adapter develops a measurin g instrument, the cross-cultural adaption scale (XCA), a number of statements about the cultural affinity of the object evaluated. The pretest portion of the sample tests the clarity and understandability of the rating scale to be used for evaluating the instructional materials; the pilot group analyzes the original version of the instructional mater ials, determines the criteria for change, and analyzes the adapted version in terms of these criteria; the control group is administered the original version of the learning materials; and the experimental group is administered the adapted version. Finally, the responses obtained from the XRA rating scale and discussions of both the experimental and control groups are studied and group differences are ev aluated according to cultural conflicts met with each version. With this data, the preferred combination of elements is constructed.^ieng