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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 595 records · Page 33Linked to original sources
PubMed1983

Factors associated with graft rejection after HLA-identical marrow transplantation for aplastic anaemia.

One hundred and seventy-five consecutive patients with severe aplastic anaemia were given high-dose cyclophosphamide followed by marrow grafts from healthy, HLA-identical family members, and 168 lived long enough to show engraftment. In 38 patients the graft was rejected and 29 of these died. This analysis, using a binary logistic regression model, was aimed at identifying factors that predicted marrow graft rejection. Five factors correlated with graft rejection: (1) previous blood transfusion; (2) a positive relative response in mixed leucocyte culture indicating sensitization of patient against donor; (3) a low number of marrow cells used for transplantation; (4) marrow grafts from male donors; and (5) lack of infusion of viable donor buffy coat cells in addition to the marrow for transfused patients. The findings confirm the importance of transplanting early before transfusion and indicate that the greatest possible amount of donor marrow (supplemented by stem cells/lymphoid cells derived from the peripheral blood) should be obtained.

Anemia, Aplastic↗
PubMed1983

Thymosin fraction 5 does not accelerate reconstitution of immunologic reactivity after human marrow grafting.

More than 1 year is required for immunologic function to recover following human marrow grafting. In an attempt to shorten the time required for immunologic reconstitution, 14 patients were treated with thymosin fraction 5 after transplantation. Two died before administration of thymosin could be completed. In the remaining 12 patients, immunologic studies were compared to those of patients who were transplanted but did not receive thymosin. While five patients had transient elevation of in vitro lymphocyte blastogenesis during thymosin treatment, results of other immunologic studies from patients treated with thymosin were similar to those from patients not treated. The subsequent development of graft-versus-host disease, major or minor infection, and leukaemic relapse was not different between the groups. Six patients are alive and five are well without problems; one has chronic graft-versus-host disease. We conclude that thymosin fraction 5 administered as described was not toxic. Although modifying some immunological parameters, thymosin did not appear to alter the incidence of graft-versus-host disease, infection or leukaemic relapse or to accelerate immunologic reconstitution.

Adolescent↗
PubMed1983

Transfusion requirements after HLA-identical marrow transplantation in 82 patients with aplastic anemia.

Red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 13 weeks after HLA-identical marrow transplantation were studied in 82 patients with aplastic anemia. On the average, patients were given 9 units of RBCs (1-82) and 44 units of PLTS (6-468). The greatest need for support was during the first 4 weeks postgrafting. A multivariate statistical analysis of 22 variables showed that RBC and PLT requirements increased with age. In addition, RBC requirements increased if the patient had isohemagglutinins against the marrow donor's RBC, i.e., if the marrow transplant was across a major ABO barrier.

ABO Blood-Group System↗
PubMed1983

Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.

Adolescent↗
PubMed1983

Functional diversity in OKT4 and OKT8 subsets from long-term survivors after HLA-identical marrow grafting.

T and B cells from one short-term and nine long-term patients who had received HLA-identical bone marrow transplants for aplastic anemia or hematologic malignancy were studied for their ability to synthesize immunoglobulin after in vitro stimulation with pokeweed mitogen, Herpes simplex type 1 antigen, tetanus toxoid, or Epstein-Barr virus. Purified T, OKT4, OKT8, or B cells from patients were cocultured with normal T and/or B cells in the presence of the various stimulants. Multiple regulatory defects were observed in long-term patients with and without chronic graft-versus-host disease. The lymphocytes from the long-term healthy chimeras exhibited fewer defects in their ability to regulate in vitro immunoglobulin synthesis than those of patients with chronic graft-versus-host disease. These findings suggest that the presence of chronic graft-versus-host disease delays or impairs the "rematuration" of the immune system after bone marrow grafting and that the rematurational process occurs at the clonal level.

Antibodies, Monoclonal↗
PubMed1983

Cellular interactions in marrow-grafted patients. I. Impairment of cell-mediated lympholysis associated with graft-vs-host disease and the effect of interleukin 2.

Forty patients with hematologic malignancy or aplastic anemia were given allogeneic marrow after conditioning with high-dose cyclophosphamide alone or in combination with total body irradiation. Between 28 and 3857 days after transplantation, their peripheral blood mononuclear leukocytes were tested for reactivity in indirect cell-mediated lympholysis against normal leukocytes from unrelated individuals, and the results were compared to those with cells from their healthy marrow donors. An impairment of cell-mediated lympholysis was found with cells from most patients with acute and chronic graft-vs-host disease (GVHD) whereas cells from most short-term and long-term patients without GVHD had cell-mediated lympholysis reactivity comparable to that of cells from the marrow donors. When interleukin 2 was added to the mixed leukocyte cultures during the sensitization phase, the impaired cell-mediated immunity of cells from most short-term patients with acute GVHD, but not that of cells from most patients with chronic GHVD, could be restored to normal levels. These results suggest the impairment of cell-mediated immunity seen in cells of short-term patients with acute GVHD is attributable to helper cell defects or to ineffective communication between antigen-presenting cells and helper T cells. The impairment in cell-mediated immunity seen in patients with chronic GVHD, however, may reside on the effector cells (or their precursors) or may be due to the presence of suppressor cell activity.

Acute Disease↗
PubMed1983

Autologous marrow recovery and sensitization to non-HLA antigens after HLA-identical marrow transplantation for aplastic anemia.

One hundred seventy-five patients with severe aplastic anemia were treated by high-dose cyclophosphamide and HLA-A, -B, and -D-identical sibling marrow transplants. Thirty-eight patients rejected their grafts. Four of the 38 showed autologous marrow recovery as determined by blood genetic markers. The remarkable feature of one case following autologous marrow recovery was the presence of unidirectional proliferative and cytotoxic responses of circulating host lymphocytes to marrow donor lymphocytes in mixed lymphocyte culture and cell-mediated lympholysis. Presumably these responses were the result of in vivo sensitization to those non-HLA antigens for which donor and recipient differed.

Adolescent↗
PubMed1983

Impaired autologous and allogeneic mixed lymphocyte reaction in human marrow transplant recipients.

The autologous and allogeneic mixed lymphocyte reactions of enriched T to non-T cells from 54 allogeneic marrow recipients were studied. Reactivity of cells from almost all patients was severely impaired when compared with those from their marrow donors. There were no differences between lymphocyte responses of patients with and without graft-versus-host disease. However, in the autologous mixed lymphocyte reaction the impairment was more severe in cells from short-term than in those from long-term patients. Coculture experiments using enriched T or non-T cells from patients mixed with T or non-T cells from their respective marrow donors indicated that the impairment resided primarily in the responding T cells, partially in stimulating non-T cells, and perhaps also in the interactions of T and non-T cells. In the allogeneic mixed lymphocyte reaction, T cells from patients showed defective responses to normal allogeneic non-T cells. Their non-T cells, however, often had normal allogeneic stimulating capacity.

Adolescent↗
PubMed1983

The canine major histocompatibility complex. Population study of DLA-D alleles using a panel of homozygous typing cells.

The frequencies of 12 DLA-D alleles in a random canine population were determined in one-way mixed lymphocyte cultures using a panel of homozygous typing cells established in this laboratory. The homozygous typing cells served as stimulators for responder lymphocytes obtained from 160 random dogs. The results of these studies were compared to those with lymphocytes from 75 dogs in our research laboratory. DLA-D allelic frequencies were estimated by maximum likelihood techniques. The use of a relative response (RR) less than or equal to 5% as a definition of a typing response resulted in the recognition of a total allele frequency of 59% in dogs from the research laboratory. Three of the 12 DLA-D alleles were not detected. Typing responses of cells from random dogs to the 12 DLA-D alleles were determined using RRs less than or equal to 5%, less than or equal to 10%, less than or equal to 15%, and less than or equal to 20%. With RRs of less than or equal to 5%, less than or equal to 10%, and less than or equal to 15%, the total allele frequencies recognized were 39%, 47%, and 55%, respectively. Within each of these % RR ranges all but one of the DLA-D alleles were detected. With an RR less than or equal to 20% the total allele frequency recognized was 58% and all 12 alleles were detected. Our results indicate that an RR of less than or equal to 10% could be used to define a phenotypic DLA-D typing response in the dog. The level of allelic frequencies detected in both the research and random canine populations indicates the need to identify additional DLA-D alleles through expanded family studies using mixed lymphocyte culture and homozygous cell typing.

Animals↗
PubMed1983

Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One-hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.

Anemia, Aplastic↗
PubMed1983

Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse.

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2-6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.

Acute Disease↗
PubMed1983

Fanconi's anemia treated by allogeneic marrow transplantation.

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647-3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.

Anemia, Aplastic↗
PubMed1983

Identification of immunoglobulin-secreting cells among canine peripheral blood mononuclear cells by the protein A hemolytic plaque assay.

Canine peripheral blood mononuclear cells (PBMC) were assayed for plaque-forming cells either immediately after isolation or after 6 days of culture in fetal calf serum in the presence of a B cell mitogen. Immediately-assayed PBMC produced a mean of 4870 IgG-related, 1610 IgM-related, and 760 IgA-related plaques per 10(6) PBMC. Many of the plaques formed by freshly isolated PBMC, however, appeared to represent release of previously adsorbed antibody. In contrast, plaques formed by cultured cells clearly identified immunoglobulin-secreting cells. We therefore used a system with culture conditions optimized for maximum plaque production to quantify pokeweed mitogen-stimulated plaque formation by normal canine PBMC. A mean of 560 IgG, 180 IgM, and 18 IgA plaque-forming cells could be identified among PMBC of 22 normal dogs. This assay will be useful for further characterization of canine lymphocyte subpopulations and facilitate the study of immunologic disorders in canine models.

Animals↗
PubMed1983

Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.

We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.

Androgens↗
PubMed1983

Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up.

Twenty-two patients with acute lymphoblastic leukemia in second or subsequent remission and 26 with acute lymphoblastic leukemia in relapse were given cyclophosphamide (60 mg/kg on each of 2 days), total body irradiation (920 rad), and marrow transplants from HLA-identical siblings. With a minimum follow-up of more than 5 yr, an actuarial analysis shows a survival and apparent cure of 27% of the patients transplanted in remission and 15% of the patients transplanted in relapse.

Bone Marrow Transplantation↗
PubMed1983

Bilateral diffuse pulmonary ectopic ossification after marrow allograft in a dog. Evidence for allotransplantation of hemopoietic and mesenchymal stem cells.

In light of recent studies showing successful transplantation of both bony and stromal elements by marrow transplantation, we report an unexpected phenomenon occurring in a canine radiation chimera. Nine hundred fifty-six days after a successful and uneventful DLA-matched marrow allograft, a dog suddenly died of respiratory failure. Autopsy revealed extensive ossification of the lungs with multiple sites of trilineage marrow engraftment. The entire complement of bony elements can apparently be allografted using marrow grafting techniques.

Animals↗