Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac pathologic findings were analyzed in 22 necropsy cases from a series of 29 patients with leukemia, aplastic anemia, or metastatic cancer who had been treated with ablative therapy followed by bone marrow transplantation. Some cardiac alterations were similar to those that occur in patients with hematologic and neoplastic diseases not treated with bone marrow transplantation, and consisted of cardiomegaly, cardiac atrophy, hemorrhage, foci of necrosis due to shock associated with sepsis or hepatic failure, myocardial abscesses secondary to systemic candidiasis or staphylococcal infection, fibrinous pericarditis, and hemosiderosis. Other cardiac alterations were more specifically related to factors associated with transplantation procedure. Six patients exhibited a distinctive interstitial reactive change characterized by the presence of (1) moderate to large numbers of Anitschkow cells, occurring alone or in small cellular aggregates and histiocytes, histiocytic cells with nuclei of the Anitschkow type, lymphoid cells, and plasma cells, and (2) nuclei of the Anitschkow type in cardiac vascular and endocardial smooth muscle, endothelial and Schwann cells, and occasional cardiac muscle cells. This alteration may have been induced by abnormal immune mechanisms, as suggested by the observation that five of the six patients with interstitial change had clinical evidence of graft-versus-host disease. Two patients developed fatal congestive cardiac failure in the early post-transplant period and exhibited myocardial damage with histologic and post-transplant period features indicative of severe acute injury. Findings in these two patients consisted of necrotic muscle cells, which exhibited multiple contraction bands, diastase-resistant PAS staining, and intracellular fibrin deposits; microthrombi, which were composed of fibrin and occasionally of fibrin and platelets; and extravasated erythrocytes and fibrin strands in the interstitium. One of the two patients also exhibited unusual nuclear alterations, which were characterized by replacement of normal chromatin by palely stained fibrous and filamentous material. Clinicopathologic analysis strongly suggested that the fatal cardiotoxicity in both patients resulted primarily from effects of high doses of cyclophosphamide, which were administered as part of a four drug regimen that provided tumor ablation and immunosuppression for bone marrow transplantation. Our findings emphasize the need for less toxic antineoplastic and immunosuppressive therapy for use in bone marrow transplantation procedures.
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PMID:Cardiac pathologic findings in patients treated with bone marrow transplantation. 110 69

Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.
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PMID:A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases. 267 Feb 9

Between October 1983 and October 1985, 12 allogeneic bone marrow transplantations from HLA-identical siblings were performed for treatment of malignant disease (11 haemopoietic malignancies) or severe aplastic anaemia (1 case). All patients showed prompt and complete engraftment of donor cells on average around day 17 after transplantation. 10 patients are alive and well 50-760 days after transplantation, without any signs of recurrence and partly without immunosuppressive therapy. Two patients died, one due to relapse of the leukaemia, and one as a result of CMV interstitial pneumonia. Graft versus host disease was seen in 6 of the 12 patients. Additional immunosuppressive therapy was necessary in 4 of them. The incidence of idiopathic interstitial pneumonia in our group of patients was low (two cases). Also tested was an experimental protocol for the treatment of chemotherapy-resistant metastatic solid tumours. After removal of all clinically detectable tumour tissue by maximal surgical therapy in 5 patients, residual systemic metastases were treated by means of total body irradiation and high-dose cyclophosphamide, followed by autologous bone marrow transplantation with curative intention. Relapse occurred in 4 patients between day 100 and 720 after BMT bone marrow transplantation. Only one patient remains without sign of relapse.
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PMID:[Experience using bone marrow transplantation in the treatment of hematologic neoplasms and solid tumors]. 355 39

Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.
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PMID:Tolerance and autoimmunity to erythroid differentiation (B-G) major histocompatibility complex alloantigens of the chicken. 612 77

Inhibitory effects on some immunological responses and MethA fibrosarcoma in the double grafted tumor system in mice were compared between 6-mercaptopurine (6-MP) and its novel water-soluble derivative, gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG). The dose-dependent inhibitory effects by 6-MPG on the hemagglutinin response to SRBC, DTH reaction to MBSA, contact sensitivity to oxazolone, GVH response and growth of the primary tumor were 3-10 times weaker than those by 6-MP, probably reflecting the difference in their cytotoxicities antimetabolites. However, the two drugs were nearly equipotent in reproducing inhibition of the secondary tumor growth, which is a host-mediated immunological response to tumor antigen as shown by its dependency on the primary inoculation with 1 x 10(4) or more MethA cells and by the production of anti-tumor splenocytes in tumor-bearing animals (the Winn assay). Thus, 6-MPG may point to the direction of derivatization towards anti-tumor immunopotentiators with an improved therapeutic index.
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PMID:Augmentation of tumor immunity by 6-MPG, a water-soluble derivative of 6-mercaptopurine, in mice. 893 10

Bone marrow transplantation is now being performed in children having a variety of hematologic malignancies and solid tumors. Marrow donors for patients with hematologic malignancies are usually allogeneic, including HLA-identical siblings, one-antigen mismatched family members, unrelated matched donors, or in some situations, two- or three-antigen mismatched family member donors. Umbilical cord blood is being explored as a source of hematopoietic reconstitution for some allogeneic transplants. Recipients with solid tumors most often receive autologous marrow or PBSC grafts. Posttransplant complications continue to include acute and chronic GVHD, infections, prolonged immunodeficiency, and recurrent malignancy. Because children are now surviving longer after transplantation, a variety of delayed effects are becoming apparent. These include, but may not be limited to, neuroendocrine dysfunction, neuropsychological effects, and ocular and pulmonary dysfunction. Secondary malignancies are now also becoming apparent, particularly among patients surviving more than 10 years after transplantation. Despite these known problems, marrow transplantation remains the treatment of choice for patients who relapse from conventional chemotherapy and for patients with CML in chronic phase and AML in first remission. Research continues to develop methods to decrease posttransplant complications and, hence, increase the probability of long-term disease-free survival.
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PMID:Bone marrow transplantation for pediatric malignancies. 928 97

Infusion of donor leukocytes, to provoke graft-versus-host disease and a graft versus leukemia effect, is remarkably effective in the treatment of some forms of relapsed hematological malignancies after transplantation of allogeneic stem cells. In this commentary I argue that the variable susceptibility of tumor cells to donor leukocyte infusions can be predicted on the basis of their localization to the T cell areas of secondary lymphoid organs and the amount of donor chimerism in the patient. This conclusion leads to the hypothesis that it may be possible to modulate graft-versus-leukemia reactions in a controlled and predictable fashion.
Cancer Metastasis Rev 1998 Jun
PMID:Geographical considerations regarding donor leukocyte infusions for the treatment of relapsed hematological malignancies. 977 Jan 22

This study demonstrates that systemic interleukin 2 (IL-2) can decrease the homing of syngeneic immune T cells to the target organ of metastases and accelerate unwanted side effects of allogeneic immune T cells. As a tumor system, we used the well-characterized highly aggressive DBA/2 mouse leukemia ESb and its less aggressive adhesion variant, ESb-MP. Systemic IL-2 treatment was performed with recombinant human interleukin-2 (Proleukin), which was slowly released via an implanted osmotic pump or was modified with polyethylene glycol (PEG-IL-2) to achieve constant plasma levels. Allogeneic B10.D2 antitumor immune spleen cells (ISPL cells) exerted strong graft-versus-leukemia (GvL) reactivity after adoptive transfer into late-stage ESb-MP tumor-bearing DBA/2 mice. Mls(a) superantigen-reactive vbeta6 donor T cells were not eliminated or tolerized by in vivo priming with the tumor cells and were present in active proliferation in liver infiltrates. When exogenous PEG-IL-2 or Proleukin was applied in addition to ISPL cells in such mice, the strong GvL-mediated protective immunity was converted into a fatal graft-versus-host disease. IL-2 treatment alone had no toxic effect and caused a moderate protection effect in the absence of an effect on local tumor growth. Potentiation of GvH reactivity of B10.D2 ISPL by PEG-IL-2 was proven in non-tumor-bearing DBA/2 mice, in which graft-versus-host disease was characterized by: (a) heavy hepatic lymphocytic infiltration, (b) irreversible increase of serum glutamate-oxalacetate-transaminase and glutamate-pyruvate-transaminase levels, (c) weight loss, and (d) death. Antagonistic effects of systemic IL-2 on GvL were observed with syngeneic DBA/2 anti-ESb immune peritoneal effector cells (PECs). There was a detrimental effect of systemic IL-2 on liver target organ infiltration by immune T cells causing, at day 6 after transfer, a drop from 20-30 CD4 or CD8 T cells per liver lobule in the PEC group to <5 in the PEC plus IL-2 group. The results emphasize the importance of a better understanding of IL-2 function in vivo and of its interaction with immune cell function to improve protocols for optimal application in the clinic to achieve maximal GvL effects.
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PMID:Antagonistic effects of systemic interleukin 2 on immune Tcell-mediated graft-versus-leukemia reactivity. 982 26

A 44-year-old patient who had had acute monoblastic leukemia developed an osteosarcoma of the pelvic bones 5 years after an allogeneic bone marrow transplant from his HLA-identical sister. He had additionally received superficial cutaneous radiation of the legs and pelvis, over the 3 weeks prior to total body irradiation (TBI), because of cutaneous leukemic lesions. The tumor was a fibrohistiocytomatous osteogenic sarcoma. The first lesion was in the right ilium, and a second lesion appeared 18 months later, symmetrically on the left ilium. Despite treatment, the patient died from metastases. At the time of diagnosis of radiation-induced sarcoma, the patient was free of leukemia and had several risk factors already reported to favor the development of solid tumors in stem cell recipients. These include acute leukemia, TBI and graft-versus-host disease. As he developed symmetrical lesions of the pelvic bone, and because of the histology of the radiation-induced tumor, we assumed that the additional radiation of the skin prior to TBI may have contributed to the pathogenesis of this malignant fibrous histiocytoma. Therefore, the risk/benefit ratio should be carefully considered in unusual indications. These patients should benefit from a close follow-up of the superimposed areas.
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PMID:Radiation-induced bone sarcoma following total body irradiation: role of additional radiation on localized areas. 1080 73

Cell therapy with allogeneic donor cells mismatched for minor histocompatible (MiHC) antigens was applied to a murine mammary carcinoma (4T1) model to test the feasibility of graft versus tumor (GVT) effect against metastatic epithelial tumor cells. BALB/c mice bearing a 4T1 tumor of BALB/c origin were given syngeneic or MiHC-mismatched splenocytes. GVT effects were determined in secondary recipients of adoptively transferred lung cells derived from primary hosts who had previously been inoculated intravenously with 4T1 cells, and injected with one of the following: 1) naive BALB/c splenocytes, 2) naive DBA/2 splenocytes, 3) 4T1-immune DBA/2 splenocytes, or 4) DBA/2 splenocytes immunized with host-derived BABL/c spleen cells. Naive DBA/2 splenocytes inhibited tumor growth only slightly and only slightly prolonged the survival of secondary recipients, in comparison with fully matched tumor/host BALB/c spleen cells. An efficient GVT reaction was demonstrated in vitro and in vivo with MiHC-mismatched DBA/2 splenocytes from mice presensitized by multiple injections of irradiated tumor or BALB/c-derived spleen cells. All 30 mice adoptively inoculated with lung cells from primary hosts that had previously been treated with these presensitized effector cells were tumor free for >250 days. Secondary recipients inoculated with lung cells from mice given naive BALB/c or DBA/2 spleen cells died of metastatic tumors within 33 to 46 days. These results suggest that preimmunized donor cells represent an effective tool against metastatic disease; hence, the next goal should be to control graft-versus-host disease while exploiting the GVT potential.
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PMID:Cell therapy with preimmunized effector cells mismatched for minor histocompatible antigens in the treatment of a murine mammary carcinoma. 1126 65


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