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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

898 records · Page 50Linked to original sources
PubMedDate not supplied

Treatment of non-Hodgkin's lymphoma with chemoradiotherapy and allogenic marrow transplantation.

Twenty patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Four patients remain alive in complete remission from 153 to 784 days after transplant. The reason for failure in eight cases was persistence or relapse of lymphoma. In the other eight cases, death was due to a complication of the transplant procedure including interstitial pneumonia, veno-occlusive disease of the liver, graft-versus-host disease, or infection. These results appear similar to those previously observed in patients with acute leukemia in relapse in that a small but significant proportion of patients with otherwise end-stage disease may achieve prolonged complete remission after intensive chemoradiotherapy and allogeneic marrow transplantation.

Adolescent↗
PubMedDate not supplied

Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: classification, morphology, clinical presentation and response to chemotherapy.

Forty cases of naturally occurring canine lymphoma were studied using a panel of murine monoclonal antibodies which identify defined subsets of normal canine lymphocytes. The distribution of phenotypes was similar to that which is seen in man in that the majority (78 per cent) of canine lymphomas were of B-cell origin but a definite minority were phenotypically of T-cell (10 per cent) or non-B, non-T-cell (12 per cent) origin. The expression of Ia-like antigens was restricted to B-cell neoplasms. Within each histologic subgroup of canine lymphomas there was considerable heterogeneity of cell surface marker expression. Immunophenotype appeared to correlate with clinical presentation. Finally, the reactivity of lymphoma cells with murine monoclonal antibody DLy-6, an antibody which appears to react with a differentiation antigen on canine B and T cells, strongly predicted the outcome of initial induction chemotherapy in that all ten evaluable dogs with DLy-6-tumors achieved complete responses to initial chemotherapy while only four of 11 dogs with DLy-6+ tumors responded completely.

Animals↗
PubMedDate not supplied

Marrow transplantation for severe aplastic anemia associated with exposure to quinacrine.

Severe aplastic anemia developed in a patient after administration of quinacrine for treatment of discoid lupus erythematosus. Marrow transplantation was performed from an HLA genotypically identical sister after conditioning with cyclophosphamide. Quinacrine which was accumulated in the patient tissues did not interfere with engraftment, suggesting that the drug has no direct cytotoxic effect on hematopoietic stem cells. This study extends our previous observation that severe aplastic anemia acquired after exposure to drugs or toxins can be cured by marrow transplantation.

Adult↗
PubMedDate not supplied

Organization of the canine major histocompatibility complex: current perspectives.

The dog is a valuable model for studying several human diseases as well as one of the most important models for organ transplantation. Important to understanding the pathophysiology or development of some of these diseases is an understanding of the canine major histocompatibility complex (MHC) or dog leukocyte antigen (DLA). Initial characterization of the DLA involved primarily cellular, serological, and biochemical analyses. Later a molecular analysis of the DLA region was begun. There are at least four complete class I genes: DLA-88, DLA-12, DLA-64, and DLA-79. DLA-88 is highly polymorphic, with more than 40 alleles obtained from an examination of 50 mixed breed dogs. The other class I loci are less polymorphic, with fewer than 12 alleles each. In the class II region there is one complete DRB gene called DLA-DRB1 with at least 24 alleles and one full-length DQB gene, DLA-DQB1, with 20 alleles characterized to date. DLA-DQA is less polymorphic with nine alleles and DLA-DRA appears monomorphic. Two highly polymorphic canine microsatellite markers, one located in the class I region and one located in the class II region, can be used to identify DLA-matched and -mismatched dogs within families for organ transplantation experiments. Future projects include mapping the DLA region by pulsed-field gel electrophoresis and using a recently constructed canine bacterial artificial chromosome (BAC) library to search for new genes within the DLA. The dog has been a useful model for understanding several human diseases such as gluten-sensitive enteropathy (Hall and Batt 1990), rheumatoid arthritis (Halliwell et al. 1972), narcolepsy (Tafti et al. 1996), and systemic lupus erythematosus (Lewis and Schwartz 1971, Teichner et al. 1990), as well as an important model for solid organ and hematopoietic stem cell transplantation (Storb and Deeg 1985). Much of the impetus behind efforts to characterize the canine MHC comes from its importance in transplantation. In spite of the dog's importance in studying human disease and in immunology, molecular analysis of the DLA has lagged behind that of the mouse and human as well as several agricultural animals.

Animals↗
PubMedDate not supplied

Bone marrow transplantation for aplastic anemia.

The increased survival of aplastic anemia patients treated by human leukocyte antigens (HLA)-identical marrow transplants is due in part to a decrease in the incidence of graft rejection. The decrease in rejection, in turn, results from the more judicious use of transfusions before transplant, the removal of sensitizing white blood cells from transfusion products, and improvements in the immunosuppressive conditioning programs used to prepare patients for transplant. In regards to the latter, radiation-based programs have been effective, although a cyclophosphamide/antithymocyte globulin program begins to look impressive with only one rejection among 33 patients transplanted. In regards to transfusions before transplant, in vitro radiation of all blood products may further reduce the risk of sensitization to minor histocompatibility antigens in the future. The incidence and severity of acute graft-versus-host disease (GvHD) have declined with the use of the methotrexate/cyclosporine regimen, and this has also contributed to improved survival. Chronic GvHD is difficult to treat and future emphasis should be on prevention rather than on treatment. Whether an extended course of cyclosporine beyond 6 mo after transplant will reduce the risk of chronic GvHD is under study. As more and more patients become long-term survivors, problems from long-term sequelae from the conditioning programs and from postgrafting immunosuppression must be considered, in particular secondary malignancies. Perhaps less toxic conditioning programs can be designed. Because of the higher likelihood of causing secondary cancer, possible deleterious effects on growth and development for pediatric patients, and the problem of sterility, radiation-based regimens should not be used in HLA-identical recipients.

Anemia, Aplastic↗
PubMedDate not supplied

Implanted right atrial catheters for continuous infusion of solutions into dogs.

Silastic catheters were fabricated and aseptically implanted through the skin into the jugular vein of 64 dogs with the intravascular tip located in the right atrium. Solutions were infused through the catheter at 2 to 2.5 mL/h by a portable pump worn by the dog. Following 9.2 Gy total body irradiation (TBI) and allogeneic bone marrow transplantation (BMT), succinyl acetone, an experimental chemotherapeutic agent, was infused into 34 dogs. Hematopoietic growth factors were infused into an additional 30 dogs, two of which had 9.2 Gy TBI and an autologous BMT, and four of which had 4.0 Gy TBI and no BMT. All dogs received continuous oral and parenteral antibiotics while the catheters were in place. All catheters functioned well until electively removed (n = 28) or until the dogs died or were euthanized (n = 36) at 12 to 68 days after implantation. Mean length of catheter function was 30.3 +/- 1.5 (SEM) days. No catheters were dislodged and there was no evidence of catheter-related blood loss or sepsis. Semiquantitative cultures of 5 catheters were negative, but Staphylococcus epidermidis was isolated from 3 of 7 catheters cultured in broth. Six dogs had thrombosis adjacent to the intravascular catheter tip. The catheters were well tolerated and facilitated successful long-term infusion of solutions into dogs.

Animals↗
PubMedDate not supplied

Aplastic anemia.

Aplastic anemia is a disease that presents with a hypocellular marrow and peripheral blood pancytopenia. In Europe and the United States, it has an age-adjusted incidence per million population per year of 2.2 compared to 11.0 in Japan and Korea. Pathogenic mechanisms are varied and include intrinsic defects of hematopoietic stem cells, defects in the marrow microenvironment, and abnormal humoral or cellular immune control of hematopoiesis. In most patients, aplastic anemia is of unknown etiology, whereas in some, the disease can be related to infections, drugs and chemicals, and hereditary causes. Therapy for aplastic anemia includes blood component transfusions, antibiotics, androgenic steroids, and corticosteroids. With supportive care, most patients with aplastic anemia die within a year of diagnosis, and only approximately 20% of patients are surviving, although often with persisting hematologic abnormalities. The use of hematopoietic growth factors has shown, for the most part, only transient beneficial effects. More definitive therapy has been the use of immunosuppressive agents including antithymocyte globulin, cyclosporine, and cyclophosphamide. With immunosuppressive therapy, a variable proportion of patients respond to therapy, ranging from 20% to 80%. However, although responses may be frequent, long-term outlook is guarded because some patients may relapse with aplastic anemia, whereas others may go on to have a clonal disorder develop, including myelodysplasia, leukemia, or paroxysmal nocturnal hemoglobinuria. As a result, survival estimates at 15 to 18 years may be only on the order of 30%. More definitive therapy has been with transplants of hematopoietic stem cells from allogeneic donors. Transplants are carried out after high-dose immunosuppressive conditioning programs. Best current results show long-term, event-free survivals with successful allografts on the order of 90%.

Anemia, Aplastic↗