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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 775 records · Page 43Linked to original sources
PubMed1977

Studies on cellular inhibition and serum-blocking factors in 28 human patients given marrow grafts from HLA identical siblings.

Fifteen patients with aplastic anemia and 13 with acute leukemia were studied 36 to 1547 days after treatment with high-dose cyclophosphamide and/or total-body irradiation and marrow transplantation from HLA identical siblings. Peripheral blood lymphocytes from patients and normals (marrow donors and healthy unrelated individuals) were tested for cell inhibition (CI) of cultured skin fibroblasts from both patients and donors by using the microcytotoxicity assay. In addition, blocking of CI by factors in patient serum was studied. Three groups of patients were studied. Patients in group I were stable long-term survivors without evidence of graft-vs-host diseases (GVHD) between 250 to 1547 days postgrafting. Patients in group II were short-term survivors with or without acute GVHD between 36 and 144 days postgrafting. Patients in group III had chronic GVHD either at the time of testing or developed chronic GVHD subsequent to CI testing between days 61 and 960 postgrafting. Eleven of 14 patients in group I showed absence of both CI and serum blocking and three showed CI and blocking. Patients in group II without acute GVHD showed absence of CI and serum blocking on three occasions, presence of CI and blocking on four occasions, and CI without blocking on three occasions. Patients in group II with acute GVHD showed absence of CI on one occasion and presence of CI and blocking on three occasions. Patients in group III showed absence of CI and blocking on seven occasions and CI without blocking on two occasions. These results suggest that the maintenance of stable graft-host tolerance in long-term survivors after marrow grafting from HLA identical donors does not depend on the presence of serum-blocking factors. Short-term survivors with and without GVHD showed a spectrum of in vitro reactivity with 50% of the patients showing serum-blocking factors, and these results did not appear to be correlated with presence or absence of acute GVHD. Finally, results of the microcytotoxicity assays failed to provide insight into the mechanism of chronic GVHD.

Adolescent↗
PubMed1977

Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation.

Baboons were given 1200 R total body irradiation from two opposing 60Co sources. Three animals were given supportive therapy only and died, as expected, within 8 days of irradiation with profound marrow hypoplasia. Five baboons were cross-circulated with unirradiated partners and died within 14 days with evidence suggestive of graft-versus-host disease. Their marrows were repopulated with hemopoietic precursor cells, and three of the five had rises in peripheral white blood cell counts to more than 1500/cu mm before death. These results are compatible with the presence of hemopoietic stem cells in the peripheral blood of a nonhuman primate, the baboon.

ABO Blood-Group System↗
PubMed1976

Marrow grafts between canine litter-mates homozygous or heterozygous for lymphocyte-defined histocompatibility antigens.

Hemopoietic grafts following 1,200 R of total body irradiation were carried out between canine littermates homozygous or heterozygous for lymphocyte defined (LD) antigens of the major histocompatibility complex (MHC). In all but five of the 25 pairs studied, LD homozygous dogs were also homozygous for serologically defined (SD) antigens of the MHC. Results of transplants were compared with previous results obtained in littermate pairs matched or mismatched for the MHC. Two groups of recipients were studied. Of 14 LD homozygous recipients in group 1 given grafts from LD heterozygous donors, 12 died between 8 and 193 days and two survived more than 238 and 627 days. The most frequent cause of death was graft-versus-host disease (GVHD). Survival was significantly shorter (P less than 0.005) than that of dogs given grafts from matched littermates and not different (P congruent to 0.5) from that of dogs given grafts from mismatched littermates. Survival of 11 LD heterozygous recipients in group 2 given grafts from LD homozygous donors was not different from that of dogs in group 1 (P congruent to 0.5). The results indicate that the LD loci detected by mixed leukocyte culture are not the principal determinants within the MHC that are responsible for GVHD.

Animals↗
PubMed1976

Correlation of the relative response index with marrow graft rejection in patients with aplastic anemia.

Thirty-four patients with severe aplastic anemia were treated with cyclophosphamide or total body irradiation and an infusion of marrow from a genotypically HLA-identical sibling donor. Engraftment occurred in all patients but rejection was noted in 12. Mixed leukocyte culture (MLC) tests undertaken before grafting to determine donor-recipient histocompatibility were analyzed retrospectively. The response of patient cells to sibling cells in mixed culture was compared to the response of patient cells to cells of an unrelated individual and expressed as a relative response index (RRI). Of the 12 patients who showed positive RRI to donor leukocytes in pregraft MLCs, 9 rejected their grafts, wheras of 23 patients with negative RRI only three rejected their grafts (P LESS THAN 0.005). The results suggest that the MLC test can detect individuals who are most likely to reject their HLA identical sibling graft.

Adolescent↗
PubMed1976

Severe hereditary haemolytic anaemica in dogs treated by marrow trasplantation.

Severe hereditary haemolytic anaemia related to pyruvate kinase deficiency occurs in Basenji dogs homozygous for this autosomal recessive defect. In the current study, three anaemic dogs were treated by total body irradiation and marrow transplantation from non-anaemic histocompatible littermates with resultant complete correction of their haemolytic anaemia. The possible use of marrow transplantation for life-threatening haemolytic anaemias in man is discussed.

Anemia, Hemolytic↗
PubMed1976

Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia.

Seventy-six patients, aged 2 to 17 years, were treated with bone marrow transplantation for severe aplastic anaemia or acute leukaemia refractory to conventional therapy. 16 of the 22 patients (73%) who received marrow transplantations for aplastic anaemia are surviving, 12 of these for over one year. In acute leukaemia, using preparation with cyclophosphamide and total body irradiation, 8 of 33 patients (24%) receiving allogeneic and 5 of 8 (63%) receiving syngeneic transplantations are continuing in remission from 3 months to beyond 2 years. The longest continuing remission off therapy is now over 4 1/2 years after preparation with total body irradiation. The major causes of failure remain graft-versus-host disease, infection, graft rejection (aplastic anaemia), and leukaemic relapse.

Adolescent↗
PubMed1976

Paroxysmal nocturanal hemoglobinuria and marrow failure treated by infusion of marrow from an identical twin.

An 18-year-old white Canadian male patient with paroxysmal nocturnal hemoglobinuria and refractory marrow failure received a marrow infusion from his normal identical twin brother without prior ablation of the patient's marrow by drugs or irradiation. After 2 years of follow-up, the patient is well with no evidence of clinical disease or significant hematological abnormality. The results suggest that normal marrow stem cells can have a selective advantage over the abnormal paroxysmall nocturnal hemoglobinuria clone.

Adolescent↗
PubMed1976

Use of antithymocyte serum in clinical and experimental marrow transplantation.

Pre-sensitization was investigated in the dog marrow transplant model with donor and recipient mismatching at the canine major histocompatibility complex (MHC). Various prophylactic immunosuppressive regimes were used and it was concluded from these regimes that sensitization to histocompatibility antigens could be abrogated by a combination of procarbazine and antithymocyte serum (ATS) together, before total body irradiation. Subsequent work in humans showed that rejection of a bone marrow graft can be successfully treated by using the procarbazine-antithymocyte clobulin regime and a second transplant. Based upon animal studies, attempts were made to prevent graft-versus-host disease in humans by the use of methotrexate following grafting. Despite matching at the MHC and the use of methotrexate some recipients developed graft-versus-host disease with a fatal outcome. Further work using ATS in the immediate pre- and post-grafting period was inconclusive. Accordingly ATS was used in animals once graft-versus-host disease became manifest with drmatic improvement in clinical status. As a result it was decided to treat all patients who developed graft-versus-host disease with antithymocyte globulin (ATG). Under ATG therpy twelve out of nineteen patients showed complete resolution, and five showed improvement. Six patients became long term survivors. Of the remaining 13, 11 died on interstitial pneumonitis, and two of fungal and bacterial infections. ATG in estblished graft-versus-host disease appears capable of modigying an otherwise fatal disease in a therpeutically beneficial manner.

Animals↗
PubMed1976

Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle.

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

Adolescent↗