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Biomedical subjects

M E Trigg

Publications and source records attributed to M E Trigg.

At least 73 records · Page 4Linked to original sources
PubMed1987

Triple lumen venous access for pediatric bone marrow transplantation candidates.

Multiple routes of vascular access are required in children undergoing bone marrow transplantation to facilitate total parenteral nutrition (TPN); blood withdrawal; and administration of blood products, antibiotics, fluids, and immunosuppressive drugs. Placement of multiple catheters frequently requires multiple venotomies in separate vessels. We have found that both a Broviac catheter and pediatric dual-lumen Raaf catheter can be placed through separate venotomies in the external jugular vein, which provides sufficient routes of vascular access without complications. This technique places only one vessel at risk while minimizing the chance for infection by utilizing two exit sites. We consider this to be the procedure of choice in young patients requiring multiple routes of vascular access.

Bone Marrow Transplantation↗
PubMed1987

Immunologic studies of lymph node lymphocytes in the generalized lymphadenopathy syndrome.

A generalized lymphadenopathy syndrome (GLS) occurs in persons at high risk for development of acquired immunodeficiency syndrome (AIDS). The natural history and immunologic status of patients with GLS are not fully known, although in some persons GLS may progress to full AIDS. We present the clinical and immunologic findings in two children with severe hemophilia A with nonprogressive GLS for 18-24 months. The functional activity in vitro of lymphocytes from both peripheral blood and biopsied lymph nodes were compared. The peripheral blood lymphocytes responded normally to both mitogens and antigens; lymph node lymphocytes failed to respond to antigens, but did respond to mitogens. The implications of these abnormalities for understanding the pathogenesis of GLS are discussed.

AIDS-Related Complex↗
PubMed1987

Haploidentical bone marrow transplantation for osteopetrosis.

HLA-matched bone marrow transplantation is an effective form of treatment for some patients with malignant osteopetrosis, a defect of osteoclast function. Following transplant, normal osteoclasts differentiate from donor-derived marrow stem cells and can function normally in some of these patients. For patients without an HLA-matched marrow donor, pharmacologic treatments have not yet proved effective. This article demonstrates that normal osteoclast function can be obtained following the transplantation of HLA-nonidentical marrow that has been purged of T lymphocytes in vitro.

Antilymphocyte Serum↗
PubMed1987

Immunologic reconstitution after haploidentical bone marrow transplantation for immune deficiency disorders: treatment of bone marrow cells with monoclonal antibody CT-2 and complement.

Patients with congenital T lymphocyte deficiency disorders received transplants with parental bone marrow depleted of mature T cells by the use of an anti-T cell monoclonal antibody (CT-2) and complement. Our results with 16 consecutive patients (20 transplants) showed rapid engraftment of donor cells; cytoreduction (busulfan, cytosine arabinoside [ara-C], cyclophosphamide) was used in six transplants, and marrow ablation was used in six (ara-C, cyclophosphamide, 1,365-cGy total body irradiation). No patient received prophylactic anti-graft-v-host disease (GVHD) therapy posttransplant, and only one patient developed significant GVHD, which involved the skin, liver, and gastrointestinal tract. Seven others showed some manifestations of GVHD, but these were of minimal clinical significance and required only occasional steroid therapy. Overall, eight patients are alive and well; eight did not survive. Polyclonal immunoglobulin synthesis by donor memory B cells was seen shortly after transplantation, with peak donor-derived serum levels seen approximately 2 months after transplantation. After this initial immunoglobulin synthesis waned, another wave of B cell responses developed. This immunoglobulin response appears to be permanent. T cell functions appeared as soon as 3 weeks after transplantation. This experience in a variety of patients with combined immunodeficiency who received transplants with monoclonal antibody T cell-depleted marrow shows gratifying results with a consistent T and B cell benefit.

Adult↗
PubMed1986

Aniridia and Wilms' tumor in a child constitutionally mosaic for 11p-;12q+: a new chromosomal change also present in Wilms' tumor cells of the blastema type.

A child with congenital aniridia was assessed closely, by repeated abdominal ultrasound examinations, beginning at birth. The Wilms' tumor subsequently discovered and removed was analyzed karyotypically and found to have some cells with a terminal deletion of chromosome 11; in other cells this deletion was associated with a duplication in the long arm of chromosome 12. These findings were identical to those observed in the patient's peripheral blood mononuclear cells. This case further substantiates the association between changes in chromosome 11 and Wilms' tumor and demonstrates how chromosomal abnormalities in early infancy may lead to the development of Wilms' tumor.

Cells↗
PubMed1986

Depletion of T cells from bone marrow for allogeneic transplantation: method for treatment of bone marrow in bulk.

T lymphocytes were depleted from donor marrow for 23 patients undergoing allogeneic bone marrow transplantation using an anti-T-cell antibody, CT-2, and complement. The methodology is described in detail for in vitro depletion of large quantities of bone marrow. The extent of T-lymphocyte depletion using various T-cell markers, the percent of marrow lost in the processing and quantity of antibody, and complement needed are presented. These techniques for in vitro T-lymphocyte depletion were reproducible and did result in an average final yield of 47% of the harvested donor marrow.

Antibodies, Monoclonal↗
PubMed1986

The decision in pediatrics to go ahead with bone marrow transplant for a pediatric malignancy.

Bone marrow transplantation in pediatrics has become an accepted modality of therapy for a variety of malignant diseases. This sophisticated approach is now being used worldwide in a large number of centers for children who fail to respond to conventional therapy. In this review I have addressed the questions of when we should offer a bone marrow transplant, what medical issues impact on this decision, when such treatment is in the child's best interests and who acts for the patient during the transplant procedure. The decision to proceed with a bone marrow transplant is a complex one and requires frank discussions on a regular basis between family members and professional staff since, for many of these questions, there are no set responses.

Bone Marrow Transplantation↗
PubMed1986

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: autologous marrow recovery with specific immune sensitization to donor antigens.

Autologous marrow recovery without engraftment of donor marrow was observed after bone marrow transplantation (BMT) for two patients with acute lymphoblastic leukemia. Each had received marrow from a haploidentical mixed lymphocyte culture (MLC) reactive donor after pretransplant conditioning with total body irradiation and high-dose cyclophosphamide. To minimize graft-vs-host disease, the marrow was depleted of T cells in vitro by treatment with a monoclonal anti-T-cell antibody and complement. Two weeks after each transplant, reactive lymphocytes were noted transiently in the blood of each patient. Analysis of karyotype, HLA type, and in vitro MLC responsiveness proved the lymphocytes to be of host, not donor, origin. MLC studies showed rapid proliferative responses specifically to stimulating cells from the BMT donor, indicating in vivo sensitization to donor antigens. Return of hematopoietic function was markedly delayed, but it eventually normalized after several months, without evidence of chimerism. These studies confirm that some immune and hematopoietic stem cells of host origin survive the high-dose chemoradiotherapy used as transplant conditioning. Because these immune cells are specifically reactive to donor alloantigens, more potent suppression of host immunity may be needed to prevent nonengraftment of T-cell-depleted, HLA-mismatched bone marrow.

Adult↗
PubMed1986

In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

Acute Disease↗
PubMed1985

Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate.

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolated CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving CNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to the CNS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Relapse of host leukemic lymphoblasts following engraftment by an HLA-mismatched marrow transplant: mechanisms of escape from the "graft versus leukemia" effect.

Leukemic relapses and graft versus host disease (GvHD) remain major complications following allogeneic bone marrow transplantation for leukemia. We present clinical and laboratory details for an eight-year-old boy who received a T-cell-depleted HLA-mismatched marrow transplant as therapy for acute lymphoblastic leukemia (ALL) in second remission. Engraftment with donor marrow was prompt and without any acute GvHD. Nevertheless, the patient's original ALL recurred and proved fatal. The patient remained a chimera with persistent donor lymphocytes present at the time of posttransplant relapse and subsequent to treatment with unsuccessful reinduction chemotherapy. In vitro immune studies showed that these leukemic cells could be recognized and destroyed by the donor's lymphocytes. The relapse itself suggests, however, that the donor's lymphocytes did not effectively destroy the patient's histoincompatible ALL cells in vivo following establishment of the chimeric state. Potential mechanisms are presented to account for this presumed "escape" from the postulated "graft versus leukemia" effect.

Acute Disease↗
PubMed1985

Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants.

Nine patients received T-lymphocyte-depleted histocompatible bone marrow and 28 patients received T-lymphocyte-depleted histoincompatible bone marrow. Eight of nine patients receiving matched bone marrow quickly engrafted without severe graft-versus-host disease (GvHD). None of the eight patients received anti-GvHD prophylaxis medications. Two of these eight patients are currently alive. Nonengraftment and severe GvHD were problems seen in some of the patients given the histoincompatible bone marrow. Additional cytarabine pretransplant permitted engraftment in those patients undergoing histoincompatible transplants for treatment of malignancy, and prednisone and cyclosporine posttransplant reduced the incidence of acute GvHD in those given T-lymphocyte-depleted grafts. Seven of these 28 patients are currently alive. T-lymphocyte-depleted marrow can reduce the occurrence or prevent severe acute GvHD, especially when combined with additional prednisone and cyclosporine; however, the impact on relapse patterns and survival remains to be determined. The occurrence of nonengraftment and treatment-related lymphomas are formidable problems to overcome.

Adolescent↗
PubMed1985

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.

A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.

Adolescent↗
PubMed1985

Mismatched bone marrow transplantation in children with hematologic malignancy using T lymphocyte depleted bone marrow.

Twenty children with hematologic malignancies were treated with bone marrow transplantation using histoincompatible donor marrow depleted of T lymphocytes. CT-2 and complement were used to deplete the T lymphocytes. Engraftment was not a major problem in those receiving increased pre- and posttransplant immunosuppression. Five of the 20 children are currently alive and disease-free. Complications in the other children included engraftment problems, cyclosporin toxicity, infections, and bleeding. However, for most children, durable engraftment was seen. Thus, the nonavailability of histocompatible donors is no longer a contraindication to allogeneic bone marrow transplantation for those at high risk of relapse.

Adolescent↗
PubMed1984

Depletion of T cells from human bone marrow with monoclonal antibody CT-2 and complement.

CT-2 mouse monoclonal antibody to the E-rosette receptor was used with complement to deplete bone marrow of E-rosette-positive cells (T cells). Depletion of E-rosette-positive cells was complete and nontoxic to hematopoietic progenitor cells. Depletion of E-rosette-positive cells with CT-2 may decrease the severity of graft-versus-host disease following bone marrow transplantation and extend the application of bone marrow transplantation to those without HLA-identical donors.

Antibodies, Monoclonal↗