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Biomedical subjects

A Fefer

Publications and source records attributed to A Fefer.

At least 73 records · Page 4Linked to original sources
PubMed1984

Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody.

Two patients with acute leukemia were treated with chemoradiotherapy and allogeneic bone marrow transplantation. Despite the prophylactic use of methotrexate after grafting, both patients developed severe graft-versus-host disease that was refractory to treatment with methylprednisolone. The graft-versus-host disease was then treated with a monoclonal antibody, 64.1, that reacts with a p19 antigen on human T cells. The disease responded dramatically to this treatment, but both patients subsequently developed a fatal polyclonal lymphoproliferative disorder arising in donor-derived B cells. Hybridization studies showed Epstein-Barr virus in both tumors. The combined effect of severe end-stage graft-versus-host disease and potent immunosuppressive therapy probably resulted in a progressive immunodeficiency syndrome that abrogated the T-cell-mediated surveillance mechanism that normally modulates the proliferation of Epstein-Barr-virus-infected B lymphocytes.

Adult↗
PubMed1984

Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia. A prospective comparison.

We compared the outcome of marrow transplantation with that of continued chemotherapy for adults with acute nonlymphoblastic leukemia who achieve a first remission. From May 1977 to July 1982, 111 consecutive adults (ages 17 to 50) with newly diagnosed acute nonlymphoblastic leukemia were treated with induction chemotherapy. Ninety patients (81%) had a complete remission. Forty-four remission patients had available donors: 33 received a transplant and 11 did not. Forty-six patients in remission without matched donors were treated with continued chemotherapy. Kaplan-Meier estimates of 5-year, disease-free survival from complete remission are 49% +/- 18% for the transplant group and 20% +/- 13% for the chemotherapy group. When compared to the chemotherapy group, patients undergoing transplantation had a higher risk of dying during the first 6 months after remission induction but a lower risk of dying thereafter. Within the transplant group, only age influenced survival. Within the chemotherapy group, a leukocyte count of greater than 10 000 mm3 at diagnosis, a French-American-British (FAB) Cooperative Group morphologic status of M-4, M-5, or M-6, and the presence of infection at diagnosis were all associated with shorter survival.

Acute Disease↗
PubMed1984

Potential for specific cancer therapy with immune T lymphocytes.

In animal models, advanced disseminated tumors can be specifically eradicated by infusions of T lymphocytes immune to tumor. The most successful regimens require a relatively small tumor burden and immunosuppression of the host to augment the transfer of immunity. Since chemotherapeutic agents administered to tumor-bearing hosts can achieve both requirements, models that combine chemotherapy and immune cells have been developed and have been shown to be effective for the therapy of advanced syngeneic malignancies. Surprisingly, tumor eradication in these and similar models does not require the transfer of cytotoxic T lymphocytes. Rather, noncytotoxic T cells of the helper/inducer subset alone are sufficient, presumably mediating tumor elimination by a delayed-type hypersensitivity mechanism involving induction of host inflammatory cells. Since donor T cells must persist in the host to provide maximum benefit in therapy, the outcome of therapy is subject to both positive and negative influences within the host for a prolonged period of time. Interleukin-2 (IL-2), a T cell replication-inducing lymphokine, promotes the in vitro growth of antigen-activated T lymphocytes. T lymphocytes immune to tumor can be grown long-term in vitro in response to IL-2 and are able to mediate a specific, cell dose-dependent effect in therapy when inoculated into tumor-bearing hosts. In vitro such long-term cultured T lymphocytes are exquisitely dependent upon exogenous IL-2 for the induction of proliferation and survival. In vivo the administration of IL-2 induces the growth of similar long-term cultured T lymphocytes and, as a consequence, increases their therapeutic efficacy. Therefore, IL-2 can be utilized both in vitro and in vivo to augment specific T cell responses for the therapy of established tumors.

Animals↗
PubMed1984

Secondary malignancies after marrow transplantation.

Secondary malignancies after marrow transplantation have been observed in 20 patients: 19 patients underwent marrow transplantation for the treatment of a hemopoietic malignancy and one for aplastic anemia. All but three were given total body irradiation at doses of 8.0-15.75 Gy as part of the conditioning regimen. Secondary malignancies were composed of three groups: (a) Six patients had recurrence of leukemia (three acute lymphoblastic, two acute myeloblastic, and one chronic myelocytic) in cells of donor origin 62-1074 days after grafting. (b) Eight patients developed lymphoproliferative disorders (four of immunoblastic sarcoma type, one lymphoblastic, one follicular center cell, and one Hodgkin's lymphoma and one acute lymphoblastic leukemia) 54-730 days after grafting. In four of seven patients with appropriate studies these tumors were of donor-cell origin and in three of four tested the cells contained Epstein-Barr virus genome or expressed viral antigens. (c) Six patients developed solid tumors (two glioblastoma multiforme, two adenocarcinomas, one squamous cell carcinoma, and one sarcoma) 347-1875 days after grafting. All but two patients (one with glioblastoma and one with squamous cell carcinoma) have died. These data suggest that patients undergoing marrow transplantation for a hemopoietic malignancy may be at risk of developing secondary malignancies. The etiology appears to be multifactorial, including irradiation, immunosuppression, Epstein-Barr virus infections, and other factors.

Adolescent↗
PubMed1983

Intensification therapy for acute nonlymphoblastic leukemia in adults.

Thirty-nine adults with acute nonlymphoblastic leukemia (ANL) in complete remission (CR) for six months were considered for intensification therapy. All patients had received a high dose chemotherapeutic remission-induction regimen consisting of daunorubicin, cytosine arabinoside, 6-thioguanine, prednisone, and vincristine, followed by one consolidation course of the same drugs at reduced doses and then monthly maintenance course of low-dose chemotherapy. The intensification therapy consisted of the same intensive chemotherapy regimen utilized for remission induction in place of the sixth and 12th monthly courses of postremission induction chemotherapy. Twenty-three of the 39 patients received intensification therapy, whereas 16 patients refused or were not offered such therapy for medical reasons and, therefore, received only monthly therapy. The median remission duration of the 23 patients who received intensification therapy was 157 weeks, and 9 remain in continuous first remission at 176-285 weeks. The remission duration of the 16 patients who did not receive intensification therapy was 73 weeks (P = 0.03). Kaplan-Meier estimates of remission duration and survival from time of remission computed by including the patients who either relapsed or received bone marrow transplantation before the time of intensification (6 months) revealed a median remission duration and survival of 100 and 172 weeks for patients receiving intensification compared to 37 and 72 weeks, respectively, for patients not receiving intensification therapy. Since results in patients not receiving intensification therapy are consistent with our previous results in patients receiving the same induction and consolidation regimens without intensification, this nonrandomized study suggests that intensification therapy prolongs remission duration and survival in adults with ANL.

Acute Disease↗
PubMed1983

Mycobacterial infections in marrow transplant patients.

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

Adolescent↗
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

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↗
PubMed1982

Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation.

Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).

Adult↗
PubMed1982

Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2.

Spleen cells from C57BL/6 mice immunized in vivo with a syngeneic Friend virus-induced leukemia, FBL-3, were specifically activated by culture for 7 d with FBL-3, then nonspecifically induced to proliferate in vitro for 12 d by addition of supernatants from concanavalin A-stimulated lymphocytes containing interleukin 2 (IL-2). Such long-term cultured T lymphocytes have previously been shown to specifically lyse FBL-3 and to mediate specific adoptive therapy of advanced disseminated FBL-3 when used as an adjunct to cyclophosphamide (CY) in adoptive chemoimmunotherapy. Because the cultured cells are dependent upon IL-2 for proliferation and survival in vitro, their efficacy in vivo is potentially limited by the availability of endogenous IL-2. Thus, the aim of the current study was to determine whether exogenously administered purified IL-2 could augment the in vivo efficacy of long-term cultured T lymphocytes. Purified IL-2 alone or as an adjunct to CY as ineffective in tumor therapy. However, IL-2 was extremely effective in augmenting the efficacy of IL-2-dependent long-term cultured T lymphocytes in adoptive chemoimmunotherapy. The mechanism by which IL-2 functions in vivo is presumably by promoting in vivo growth and/or survival of adoptively transferred cells. This assumption was supported by the findings that IL-2 did not enhance the modest therapeutic efficacy of irradiated long-term cultured cells that were incapable of proliferating in the host and was ineffective in augmenting the in vivo efficacy of noncultured immune cells that are not immediately dependent upon exogenous IL-2 for survival.

Animals↗
PubMed1982

Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins.

Twelve patients in the chronic phase of Ph1 (Philadelphia)-positive chronic granulocytic leukemia (CGL) received chemoradiotherapy and marrow from their normal, identical twins. All had a complete remission, with disappearance of all Ph1-positive cells. One patient died of pneumonitis while in remission. Three had a cytogenetic relapse 22 to 30 months after grafting; only one of these three entered blast crisis and died. Eight remain in complete remission 21 to 65 months (median, 30) after transplantation. Thus, the Ph1-positive clone can be ablated and blast crisis delayed or prevented. Of 10 patients with CGL who received transplants during the terminal phase, eight died soon after, one is in complete remission 11 months after receiving a second graft, and one remains in complete remission 71 months after transplantation. This experience suggests to us that every patient with CGL and an identical twin should receive a marrow graft, preferably in the chronic phase. On the basis of our results, trials of allogeneic-marrow transplantation for CGL seem justified.

Adolescent↗