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Biomedical subjects

A Fefer

Publications and source records attributed to A Fefer.

At least 109 records · Page 6Linked to original sources
PubMed1981

Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins.

Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.

Adolescent↗
PubMed1980

Marrow transplantation in thirty "untransfused" patients with severe aplastic anemia.

Thirty patients with severe aplastic anemia had no transfusions of blood products until just before marrow transplantation from HLA-identical family members. They were conditioned for grafting with cyclophosphamide, 50 mg/kg body weight on each of 4 successive days. All 30 had prompt initial marrow engraftment, which was sustained in 27. Twenty-five of the 30 are alive between 9 to 84 (median, 19.5) months. The actuarial projection of survival for 2 to 6 years is 75%. Twenty of the 25 surviving patients have no problems. Five have chronic graft-versus-host disease, resolving in two and active in three. Five patients died with infection or hemorrhage, four of whom had graft-versus-host disease. These data show that early transplantation should be carried out before transfusions are given for any patient with severe aplastic anemia who has an HLA-identical family member. If sensitization to minor transplantation antigens contained in blood products is avoided, the incidence of marrow-graft rejection will decrease, and survival will improve.

Adolescent↗
PubMed1980

Specificity of adoptive chemoimmunotherapy of established syngeneic tumors.

To examine the specificity of adoptive chemoimmunotherapy (ACIT) of established syngeneic tumors, two noncross-reactive C57BL/6 tumors were studied: a Friend virus-induced tumor (FBL-3) and a chemically induced virus-negative tumor EL-4(G-). In vitro studies confirmed that these tumors are antigenically distinct by demonstrating that the cytotoxic responses of spleen cells from mice immunized in vivo and reexposed to tumor in vitro are immunologically specific. Studies of ACIT with cells from mice immunized in vivo demonstrated similar specificity. Mice receiving 5 x 10(6) FBL-3 on day 0 all died by day 13. Treatment on day 5 with cyclophosphamide (CY), 180 mg/kg, prolonged the median survival time (MST) to day 23. Treatment on day 5 with CY plus 2 x 10(7) normal nonimmune C57BL/6 cells or CY plus cells sensitized to EL-4(G-) had no additional effect on survival whereas 2 x 10(7) C57BL/6 cells sensitized to FBL-3 in vivo prolonged MST to day 64 and cured 13 of 32 mice. Similarly, mice given 2 x 10(5) EL-4(G-) on day 0 all died by day 16, and CY on day 5 prolonged the MST to day 22. As an adjunct to CY, 2 X 10(7) normal cells or cells sensitized to FBL-3 had a modest effect, prolonging the MST to days 37 and 36, respectively. However, treatment with CY plus 2 x 10(7) cells immune to EL-4(G-) cured 22 of 32 mice. The results demonstrate the immunologic specificity of ACIT of syngeneic tumors treated with immune syngeneic cells.

Animals↗
PubMed1980

Therapy of leukemia by nonimmune syngeneic spleen cells.

In previous studies mice bearing an established transplanted syngeneic leukemia were cured by the adoptive transfer of immune lymphoid cells inoculated as an adjunct to chemotherapy, whereas nonimmune cells had no effect. By employing a smaller initial tumor inoculum to enhance the sensitivity of the chemoimmunotherapy model, the current study demonstrated that cells from normal nonimmune donors can also eradicate tumor. Thus, adult BALB/c mice given a lethal dose (1 x 10(4)) of LSTRA on day 0 were treated on day 5 with cyclophosphamide (CY) alone or CY plus nonimmune cells. Untreated mice all died by day 10. Cy alone prolonged median survival time (MST) to day 20, but all mice died. Treatment with CY plus 1 x 10(7) nonimmune cells prolonged the MST to day 26 and cured 16 of 48 mice. The effector cells, present in the spleens of normal and nude mice, were nonadherent lymphocytes resistant to anti Thy + C. These results are consistent with this effector cell in adoptive chemoimmunotherapy being an NK cell. However, they are distinct from classical NK cells since they are not directly cytotoxic in vitro in a short term CRA and do not neutralize tumor in vivo in a Winn assay.

Animals↗
PubMed1980

Detection of early and delayed antitumor effects following curative adoptive chemoimmunotherapy of established leukemia.

Advanced disseminated leukemia can be successfully eradicated by treatment with a combination of noncurative nonlethal chemotherapy plus adoptively transferred immune cells. The time course of tumor elimination following such therapy was examined by bioassay for tumor of peripheral blood and spleen cells from treated mice. Curative treatment with adoptive chemoimmunotherapy did not immediately eliminate all leukemia. Bioassay of cells from treated mice, rather, demonstrated that, following the initial tumor lysis mediated by the chemotherapy and immune cells, a period of tumor regrowth lasting several weeks preceded ultimate tumor eradication. This transient tumor regrowth detectable by bioassay never became clinically evident in the treated mice. However, immunosuppression of mice two weeks after treatment with adoptive chemoimmunotherapy resulted in recurrence of lethal tumor. The results suggest that tumor elimination following curative adoptive chemoimmunotherapy is biphasic and that the efficacy of therapy may be subject to positive and/or negative influences over a prolonged time period.

Animals↗
PubMed1979

Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts.

To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.

Acute Disease↗
PubMed1979

Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin.

Four patients (21, 41, 13 and 38 years of age) with a history of chronic granulocytic leukemia for 12, 10, 11, and 106 months, respectively, were treated with dimethyl busulfan, cyclophosphamide, 920 rads of total-body irradiation and intravenous marrow infusion from normal, genetically identical twins. Serial chromosome analyses were performed on marrow aspirates cultured without mitotic stimulants. No Ph1-positive cells were detected in the marrows from the normal twins, whereas just before therapy, all 100 metaphases examined from each patient were Ph1-positive. Chromosome analyses were performed three to five times per patient after transplantation, and not a single Ph1-positive cell was detected. The patients remain hematologically normal 22, 23, 26 and 31 months after transplantation. The results show that the Ph1-positive clone can be eradicated by vigorous therapy and that the marrow in chronic granulocytic leukemia can be repopulated by stem cells from normal twins.

Adult↗
PubMed1979

Suppression of the in vitro secondary response to syngeneic tumor and of in vivo tumor therapy with immune cells by culture-induced suppressor cells.

Mice with advanced disseminated syngeneic tumor can be successfully treated with a combination of chemotherapy and adoptively transferred syngeneic immune cells. We have previously demonstrated that in vivo primed cells secondarily sensitized in vitro became more effective in tumor therapy, whereas primed cells cultured for 5 days without tumor stimulation became less effective than an equal number of uncultured fresh primed cells. Therefore, we examined stimulated and unstimulated cultures of tumor-primed cells for the presence of culture-induced suppressor cells, and determined whether in vivo tumor therapy with immune cells could be inhibited by concurrent inoculation of immune effector cells and cultured normal spleen cells, which contain culture-induced suppressor cells but are devoid of additional effector cells. The in vitro primary allogeneic response was suppressed by cultured normal spleen cells, or tumor-primed spleen cells previously cultured for 5 days with or without tumor stimulation. In vitro secondary sensitization to syngeneic tumor was suppressed by normal or tumor-primed cells that had previously been cultured for 5 days without stimulation. The majority of this suppression was mediated by T cells in the cultured populations. The efficacy of fresh tumor-primed cells, as well as primed cells secondarily sensitized in vitro, in adoptive chemoimmunotherapy of advanced tumor was diminished by concurrent inoculation of cultured normal cells. The cells mediating suppression of in vivo therapy required previous in vitro culture for induction, and were radiation sensitive.

Animals↗