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Biomedical subjects

A Fefer

Publications and source records attributed to A Fefer.

At least 127 records · Page 7Linked to original sources
PubMed1976

Aplastic anemia: failure of patient leukocytes to stimulate allogeneic cells in mixed leukocyte culture.

One-way mixed leukocyte cultures were used to study the ability of cells from 53 patients with aplastic anemia and 65 of their HLA-identical siblings to stimulate and to respond to cells from unrelated individuals. The capacity of leukocytes from 28 of 53 patients to stimulate was diminished or absent, wheras their ability to respond remained comparable to that of cells from their HLA-identical siblings. Leukocytes from the group of patients with the lowest peripheral lymphocyte count were least stimulatory. The results indicate that in acquired aplastic anemia there exists a dissociation between stimulation and response in mixed culture.

Anemia, Aplastic↗
PubMed1976

Marrow transplantation in aplastic anemia and leukemia.

Human marrow transplantation has resulted in observations of fundamental significance in understanding both aplastic anemia and acute leukemia. For example, the observation that transplanted marrow can grow successfully in patients with aplastic anemia indicates that the disease is due to a defect in the marrow precursor cells and not in the marrow microenvironment. Similarly, the observation of recurrent leukemia in donor cells has important implications. Nonetheless, marrow transplantation is sufficiently established therapeutically to be considered the treatment of choice for patients with severe aplastic anemia, and a realistic alternative for patients with recurrent acute leukemia. We suggest that patients be managed with regard to marrow transplantation according to the general approach outlined in Table 3. Marrow transplantation and histocompatibility typing are available at increasing numbers of institutions throughout the world. More and more patients with either severe aplastic anemia or recurrent acute leukemia should have marrow transplantation available to them when it is indicated as part of optimal management of these no longer hopeless diseases.

Adult↗
PubMed1976

Recovery from aplastic anemia following attempted marrow transplantation.

A 23-year-old man with severe idiopathic aplastic anemia was prepared for marrow transplantation by the administration of cyclophosphamide (CY) 50 mg/kg on each of 4 days. He then received an intravenous infusion of 9.5 x 10(9) marrow cells from an HL-A matched and mixed leukocyte culture non-reactive sister. The graft was successfully established as shown by cytogenetic studies but was rejected after approximately 4 weeks. In preparation for a second transplant he was given procarbazine 12.5 mg/kg and goat antihuman thymocyte globulin (ATG) 7 mg/kg administered on alternate days for a total of 4 doses of each agent. At the end of this therapy his white blood cell count was noted to be going up and the second transplant was not carried out. Complete hematologic recovery of host type marrow ensued and persists now 20 months later. The various pathophysiologic mechanisms that may be involved are discussed.

Adult↗
PubMed1976

Experience with second marrow transplants.

This report summarizes the experience with 25 patients who received a second marrow transplant. The marrow donor for the first transplant was an identical twin in four cases and a sibling matched at the major histocompatibility complex in 21 instances. The donor for the second transplant was the same as the first except for three patients whose second donor was another matched sibling. Nine patients with aplastic anemia rejected their first graft. Four of these patients were prepared for the second graft with a regimen of procarbazine and antithymocyte globulin (ATG) followed by cyclophosphamide or total body irradiation and were successfully regrafted. One rejected the second graft, two died of septicemia and one is alive and well 10 months after the second graft. Twelve patients with hematologic malignancy had a recurrence of disease after the first transplant. Despite preparation for the second graft with a variety of intensive chemotherapeutic regimens, the five patients who did not succumb to infection showed an early recurrence of disease. Four patients with hematologic malignancy had a failure of the first graft for unknown reasons, possibly related to the administration of ATG or methotrexate. One patient prepared for the second graft with procarbazine and ATG showed evidence of engraftment but died of infection. Two out of three patients given no additional preparation were successfully grafted. One died of recurrent central nervous system leukemia after 18 months and one is alive and well 26 months after the second graft.

Anemia, Aplastic↗
PubMed1976

Allogeneic marrow grafting for treatment of aplastic anemia: a follow-up on long-term survivors.

Eleven of twenty-four patients with severe aplastic anemia given marrow grafts from HLA-identical siblings between October 1970 and March 1973 are alive with normal marrow function and continued evidence of engraftment 3-5 yr later. Ten have been leading normal lives with no immunosuppressive or other drug therapy since day 100 postgrafting. One has had chronic graft-versus-host disease of the skin which is now slowly improving with no therapy. He returned to full-time employment in the summer of 1975. The long-term well-being of almost half of our initial patients emphasizes the importance of marrow transplantation for the treatment of severe aplastic anemia.

Anemia, Aplastic↗
PubMed1975

Effect of dimethylmyleran on cell-mediated immunity to a tumor allograft.

C57BL/6 mice (H-2b) were inoculated on day 0 with killed Moloney lymphoma cells (LSTRA) of BALB/c origin (H-2d), and their spleen cells were tested for reactivity against LSTRA by the 51Cr-release cytotoxicity assay. Cytotoxic reactivity of cells from ice not treated with drug was maximal by day 6 and disappeared by day 10. Cells from mice given dimethylmyleran (DDM) (12 or 16 mg/kg) on day -1 showed higher levels of cytotoxicity, whereas DMM administered on day +1 had little effect. The effect of DMM on the secondary response was tested and compared with that of cyclophosphamide (CY), 180 mg/kg. Cytotoxicity of cells from mice immunized on days 0 and 10 was maximal on day 15 and then declined. CY administered on day 11 prevented the development of any cytotoxicity and, when given on day 14 in the presence of a detectably strong secondary cytotoxic response, abolished the established response. In contrast, DMM given on day 11 delayed the onset and moderately decreased the peaks of secondary reactivity but had no effect when administered on day 14. These results showed that DMM enhanced a primary response, interfered somewhat with the development of a secondary response, and had no effect on an established secondary cell-mediated response to a tumor allograft. DMM thus was one of the rare agents with antitumor activity and little immunosuppressive action.

Animals↗
PubMed1975

Suppression of secondary cellular immunity to a tumor allograft by cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea.

C57BL/6 mice (H-2b) were immunized with lethally x-irradiated Moloney virus-induced lymphoma cells of BALB/c origin (H-2d) on Days 0 and 10 and received rug on Days 11 and 14. Their spleen cells were then tested for reactivity against Moloney virus-induced lymphoma of BALB/c origin by the 51Cr-release cytotoxicity assay. In non-drug-treated mice the secondary cytotoxic response was maximal on Days 14 to 15, declined rapidley, and recurred after Day 21. The cytotoxic effector cells were shown to be theta-bearing T-lymphocytes. Cyclophosphamide (CY), 180 mg/kg, given on Day 11, totally prevented the development of a cytotoxic response and when given on Day 14 abolished the response already established. CY, 48 mg/kg, as well as 1,3-bis(2-chloroethyl)-1-nitrosourea 33 mg/kg, were almost as suppressive. Immune mice given CY on Day 14 and reimmunized on Day 36 exhibited a normal tertiary response. Mice similarly immunized on Days 1 and 10 and given drugs on Day 14 were challenged on Day 15 with up to 3.5 x 10-8 viable Moloney virus-induced lymphoma cells of BALB/c origin. Despite H-2 incompatibility, all nonimmune control mice developed ascites and died, whereas all mice immunized but not given drug failed to develop ascites. By contrast, 17 of 34 immunized mice given CY, 180 mg/kg, and 7 of 34 given 1,3-bis(2-chloroethyl)-1-nitrosourea developed ascites. The ascites eventually regressed. THE RESULTS SHOW THAT CY and 1,3-bis(2-chloroethyl)-1-nitrosourea can suppress a secondary cellular immune response as measured by the T-cell-mediated 51Cr-release cytotoxicity assay in vitro and by viable tumor challenge in vivo.

Animals↗
PubMed1975

Syngeneic adoptive immunotherapy and chemoimmunotherapy of a Friend leukemia: requirement for T cells.

The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (10(4)) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-theta serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 10(7) FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-theta serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.

Animals↗
PubMed1975

Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells.

Myeloperoxidase, H2O2, and a halide constitute a potent antimicrobial system. A cytotoxic effect of this system on a line of mouse ascitic lymphoma cells (LSTRA) is demonstrated here using four different assay systems: 51Cr release, trypan blue exclusion, inhibition of glucose C-1 oxidation, and loss of oncogenicity for mice. Deletion of each component of the system, preheating the peroxidase, or addition of azide, cyanide, or catalase abolished the cytotoxicity. Myeloperoxidase was effective with either chloride or iodide as the halide, while lastoperoxidase was effective with iodide but not chloride. The iodinated thyroid hormones, triiodothyronine and thyroxine, could substitute for the halide, and H2O2 could be replaced by a peroxide-generating enzyme system such as glucose and glucose oxidase or by H2O2 producing bacteria such as pneumococci or streptococci. The possibility is raised that the peroxidases of inflammatory cells and certain biologic fluids may affect tumor initiation or growth in vivo.

Animals↗