Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various lymphohaematopoietic compartments represented by cells from T-cell colonies, myeloid progenitor cells (CFU-GM), erythroid progenitor cells (BFU-E), and bone marrow after short-term culture (BM) have simultaneously been analysed in 15 patients receiving 17 bone marrow transplants for Philadelphia chromosome (Ph) positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL). The marrow grafts were not T-cell depleted. Ten patients without relapse did not show any myeloid cells of host origin until their last follow-up or until death. However, in four of these patients single lymphoid host cells not carrying the Ph chromosome were found after BMT without clinical consequences. In patients with cytogenetic or haematological relapse Ph positive metaphases were first detected in any of the progenitor cell compartments along with residual donor cells in two of three patients. BM became Ph positive after various time intervals. Another patient with CML became Ph positive in all compartments investigated at the same time. The only patient with Ph positive ALL remained completely Ph negative also when haematological and clinical relapse was evident. All patients with relapse exhibited complex clonal and non-clonal chromosomal aberrations at the time of recurrence of the Ph chromosome. Such abnormalities not identical to those usually found with evolution of the disease and preferentially occurring in progenitor cells preceded the reappearance of Ph positive metaphases in one of our patients.
...
PMID:Lymphohaematopoietic chimaerism after bone marrow transplantation for chronic myeloid leukaemia: results of simultaneous cytogenetic analyses on T-cell colonies, myeloid, and erythroid progenitor cells. 187 19

This report investigates the effects of cyclosporine on the reconstitution of T lymphocytes after syngeneic bone marrow transplantation and its role in the development of a novel T cell-mediated autoimmune disease, syngeneic graft versus host disease. We analyzed the effect of CsA treatment on T lymphocyte differentiation during reconstitution after bone marrow transplantation and correlated the maturation of CD4+ and CD8+ T cell subsets with the onset of syngeneic GVHD. Administration of CsA following syngeneic bone marrow transplantation leads to a developmental arrest of mature CD4+ and CD8+ T lymphocytes in the thymus and a marked reduction in cells expressing the alpha beta T cell receptor. The reduction of CD4+ and CD8+ T cell subsets is also reflected in the peripheral lymphoid compartment with an altered CD4/CD8 ratio. Functional assessment of the cells revealed that CD8+ cells respond normally to mitogenic signalling whereas CD4+ cells exhibit marginal proliferative responses. Both subsets of T lymphocytes respond to syngeneic B lymphoblasts, comparable to the response of T lymphocytes from non-CsA-treated syngeneic BMT recipients, suggesting that autoreactive cells are produced despite CsA treatment. Following discontinuation of CsA, T cell differentiation in the thymus is rapidly restored to normal. However, concurrent with the onset of syngeneic GVHD, a compensatory insurgence of CD4+ T helper cells is observed.
...
PMID:Effect of cyclosporine on T lymphocyte development. Relationship to syngeneic graft-versus-host disease. 189 96

In conclusion, lessons from the animal model of lymphoid leukaemia suggest that in the setting of allogeneic BMT, under certain conditions GVL effects may be separable from GVHD; more specifically, GVL effects may be induced despite development of tolerance of donor cells against allogeneic host alloantigens. The latter phenomenon suggests that either curative GVL effects may be inducible despite subclinical GVHD or alternatively that effector cells of GVL may recognize different tumour-associated targets different from cell surface determinants of 'normal' alloantigens. Alternatively, effector cells of GVL may be distinguished from effector cells of GVHD. It is tempting to suggest that NK and IL2-aspirated NK cells may play a major role as effector cells of GVL in an MHC non-restricted fashion, different from classical CD8+ cytotoxic cells that certainly play a major role in GVHD and GVL. Once proven, the latter hypothesis may help develop new and safer therapeutic approaches since NK cells and products of the NK cell family are unlikely to play a major role, if any, in GVHD. The feasibility of induction of GVL-like effects by MHC non-restricted effector cells, such as that observed by CMI, most likely through cytokine-activated NK cells, seems promising because such effector mechanisms may be utilized clinically through either adoptive transfer of in vitro-activated lymphocytes or activation of lymphocytes in vivo by administration of cytokines such as IL2 and alpha IFN. Similarly, induction of CCI following ABMT may permit establishment of GVL-like effects with no major risk of GVHD. Our animal models suggest that both approaches may be beneficial and perhaps even combined. From a practical standpoint, activation of antitumour effector cells in vivo is much more feasible, in comparison with the cumbersome and expensive technologies for large-scale in vitro manipulation of IL2-activated 'LAK' cells or tumour-infiltrating lymphocytes ('TIL') at dose ranges required for obtaining clinically meaningful responses. No less important is the fact that more potent immunotherapy may be inducible by cytokine combinations (such as IL2 and alpha IFN). We are currently investigating additional cytokine combinations in order to attempt to optimize antitumour effects inducible by allogeneic and syngeneic lymphocytes since it appears logical that amplifying in vivo antitumour responses by multiple cytokine combinations may yield better antitumour effects.
...
PMID:Control of relapse due to minimal residual disease (MRD) by cell-mediated cytokine-activated immunotherapy in conjunction with bone marrow transplantation. 195 88

We have used elutriation to deplete lymphocytes from the marrow allografts of 64 patients to date. The first phase I trial (1 x 10(6) lymphocytes/kg IBW) was designed to test the procedure for potential toxicities, most notably, graft failure. Study 2 (1 x 10(6) lymphocytes/kg, no CsA) was expected to reduce potential toxicity incurred from long term immunoprophylaxis while study 3 was aimed at reducing the incidence of GVHD by further reducing lymphocyte dose (5 x 10(5)/kg). Graft lymphocyte dose was based on morphologic determination and was subsequently confirmed by limiting dilution analysis and flow cytometry. Although grafts were standardized solely by lymphocyte dose, the product was more uniform than the original harvested BM with respect to other cell populations. Nearly all study I (n = 40) and study III (n = 20) patients engrafted with a median time to ANC greater than 500/ul of 19 days. Three of the 4 patients consecutively enrolled in study II failed to engraft, thus terminating the trial. While a moderate proportion of study I patients had AGVHD (44%) with attendant morbidity, only 20% of study III patients were found to have mild AGVHD (less than or equal to stage I). To date, this cohort has no organ or chronic GVHD and no GVHD-associated morbidity. Median follow-up times for patients in studies I and III are 27 and 11 months, respectively. Overall actuarial survival (n = 60) is 42% at 38 months (38% study I, 80% study III). Good prognosis study I patients experienced 45% actuarial survival versus 9% in the poor prognostic group. While lymphocyte depletion has been effective in reducing the incidence and severity of AGVHD, new strategies are needed to address the issue of disease relapse. As with other methods, lymphocyte depletion by elutriation caused an increased rate of leukemia relapse. The actuarial probability of remaining in remission for recipients of elutriated marrow containing 1 x 10(6) and 5 x 10(5) lymphocytes/kg, respectively, were 60% and 46% at 16 months. Elutriation provides a rapid, reproducible and flexible methodology for graft manipulation which has been effective in reducing the incidence and severity of AGVHD. However, if lymphocyte depletion is to fulfill its promise as a means of reducing the overall morbidity of allogeneic BMT, new strategies may be needed to address the issue of relapse. These may include changes in marrow ablative therapy and post-graft immunosuppression. Equally as important may be the ability to further manipulate accessory cells and lymphoid populations presently excluded from the graft.
...
PMID:Using elutriation to engineer bone marrow allografts. 213 32

20 CML patients with hematological (5 pts) or only cytogenetic (15 pts) relapse occurring after allogeneic BMT have been treated with alpha-2b-interferon (IFN) at a starting dose of 5 x 10(6) IU/m2, subcutaneously, three times a week. All 5 patients with hematological relapse achieved hematological remission without reduction of bone marrow Ph1-positive cells. With a median follow-up of 43 months (range 6-48) from the hematological relapse, 3 patients are alive and 2 patients died from non-lymphoid blast crisis. 7 out of 15 patients with only cytogenetic relapse remain in hematological remission at a median of 37 months (range 3-45) from cytogenetic relapse, with 2 patients achieving complete cytogenetic remission confirmed at the molecular level by disappearance of the bcr rearranged band. With a median follow-up of 21 months (range 6-46), 8 patients progressed from cytogenetic to hematological relapse: 4 patients died from blast crisis and the other 4 patients are currently alive in chronic phase. For the 15 patients, the actuarial survival from BMT is 71% at 5 years.
...
PMID:Alpha-2b-interferon as single therapy for patients with chronic myeloid leukemia relapsing after T-cell depleted allogeneic bone marrow transplantation. 227 45

We asked in a retrospective analysis whether patients with diabetes mellitus or impaired glucose tolerance are at increased risk for morbidity and mortality after high-dose therapy followed by an autologous bone marrow transplantation. Nine patients with diabetes mellitus (n = 7) or impaired glucose tolerance (n = 2) were identified who had been treated with high-dose therapy and autologous bone marrow transplant for lymphoid malignancies. At the start of the pretransplant conditioning all patients had a Karnofsky score of at least 80 and no clinically demonstrable organ dysfunction. One patient with diabetes mellitus type I (DM I) was transplanted without any complications. The patients with diabetes mellitus type II (DM II) or an impaired glucose tolerance had complications of life-threatening infections (in 6/8), acute renal insufficiency (in 3/8), liver abnormalities with elevated liver enzymes or liver failure (in 4/8) and congestive heart failure (in 1/8). Although the complications observed are not infrequent in the transplant setting, because of the good performance status before BMT and the absence of clinically demonstrable organ impairment before transplantation, it is our impression that the presence of diabetes mellitus or glucose intolerance might be an important co-factor in the morbidity of these patients.
...
PMID:Diabetes mellitus or an impaired glucose tolerance as a potential complicating factor in patients treated with high-dose therapy and autologous bone marrow transplantation. 229 95

Thymulin, a peptide secreted by human thymic epithelial cells, circulates in peripheral blood. Levels of plasma thymulin (FTS-Zn) activity were analyzed in 21 patients with lethal combined immunodeficiency disorders who were treated with transplantation of HLA-haplotype-mismatched parental bone marrow depleted of T cells by differential agglutination with soybean agglutinin and E-rosetting (SBA-E-BMT). Among these 21 infants, 15 were patients with severe combined immunodeficiency (SCID) and 6 had combined immunodeficiency (CID) with Omenn's syndrome or CID with T cell predominance (CIDTP). In contrast to normal infants who possess high levels of plasma thymulin activity, 20 of the 21 patients demonstrated undetectable or low plasma thymulin levels for their age at admission prior to transplantation. Following SBA-E-BMT, however, thymulin became detectable in the plasma of 17 of 18 evaluable patients and reached normal or near-normal levels between 21 and 125 days posttransplant. In patients in whom the timing of engraftment could be established by emergence of donor lymphocytes, thymulin appeared in the plasma at approximately the same time as lymphoid chimerism was detected, and in all patients who were engrafted and immunologically reconstituted, the increment in thymulin levels preceded development of immune functions. These studies support the concept that normal marrow-derived cells in the graft can provide a stimulus necessary for induction of thymic epithelial secretory function in patients with thymic dysplasia. Further, immunologic reconstitution in these patients was not seen following SBA-E-BMT unless and until recovery of thymus function had been observed.
...
PMID:Evidence that appearance of thymulin in plasma follows lymphoid chimerism and precedes development of immunity in patients with lethal combined immunodeficiency transplanted with T cell-depleted haploidentical marrow. 236 51

After marrow transplantation, major histocompatibility complex (MHC)-unrestricted natural killer (NK) lymphocytes are among the first cells to appear in the circulation. After T-cell-depleted bone marrow transplantation (TD-BMT), these cells have an activated pattern of target cell killing; they also secrete lymphokines including gamma-interferon (gamma-IFN), interleukin-2 (IL-2), and tumor necrosis factor (TNF) and may have a significant role as a primary defense against viral reactivation and in the elimination of residual host malignancy. We studied 43 patients with hematologic malignancy, treated by allogeneic TD-BMT, autologous nondepleted BMT, or chemotherapy alone to investigate (a) the mechanisms underlying the generation of these activated killer cells, (b) the range of conditions under which they are produced, and (c) their surface phenotype. We showed that gamma-IFN-secreting activated killer cells with the capacity to kill MHC-nonidentical NK-resistant targets are generated 4 to 6 weeks after either allogeneic TD-BMT or autologous BMT but do not appear after treatment with chemotherapy. Production therefore is not owing to T-cell depletion per se or to host donor alloreactivity, nor is it caused by stimulation by alloantigens contained in blood product support since no significant difference exists between allograft and chemotherapy patients in the number of units of blood platelet support given in the posttreatment period. Because most patients had no evidence of stimulation from virus reactivation/infection, the phenomenon of activation therefore appears to represent posttransplant immune disregulation following repopulation of the host immune system with lymphoid subsets derived exclusively from blood and marrow. Activated killing is predominantly mediated by the CD16+ CD3- subset, but substantial activity remains in the CD16- CD3+ cell fraction. Monoclonal antibodies (MoAbs) that block interaction with class-I MHC molecules at the level of target cell (W6/32 anti-HLA class I) or effector cell (CD8) do not inhibit killing by CD16- CD3+ cells. Activated killer cells may contribute to the lower risk of relapse after marrow transplantation as compared with intensive chemotherapy.
...
PMID:Endogenously generated activated killer cells circulate after autologous and allogeneic marrow transplantation but not after chemotherapy. 249 37

This article has outlined the special problems associated with evaluation of bone marrow before and after BMT. Marrow grafting has become a major form of therapy in oncology and hematology whose potential is only beginning to be fully realized. The transplantation of healthy hematopoietic and lymphoid cells has made possible the use of otherwise superlethal doses of radiation and chemotherapy in preparing the patient for engraftment. In the case of tumors, this allows massive doses of tumorocidal therapy prior to rescue with a BMT. In the case of aplastic anemia, it allows massive immunosuppression and ablation of the residual host marrow in preparation for replacement by the healthy donor marrow. The complications of this procedure include the toxicity of chemotherapy and irradiation upon the liver, lung, and gut as well as less serious toxicity to skin and other organs. The double barrier associated with marrow transplantation consists of rejection and GVHD. Marrow graft failure occurs by two distinct mechanisms, graft resistance and graft rejection. The former is marked by a total failure of any evidence of engraftment and the latter by engraftment followed by disappearance of the graft. GVHD is the immunologic attack upon host tissues by donor lymphoid cells (predominantly mature T cells). In the acute phase, it attacks liver, skin, and gut, with the latter producing the most life-threatening syndrome. Chronic GVHD resembles scleroderma. Treatment of GVHD includes the use of prednisone, cyclosporin A, ATG, and monoclonal antilymphoid antibodies. Prevention includes the attempt to remove T cells from the donor marrow with monoclonal antibodies using complement-mediated cytolysis and other approaches such as conjugation of antibodies to ricin and other toxins. GVHD also produces severe immunosuppression in and of itself added to that produced by chemoirradiation therapy. As a result, the marrow transplant recipient is extremely susceptible to infections. During the early period, the patient is granulocytopenic and susceptible to bacterial and fungal infections, which are dealt with by antibiotics and isolation procedures. Later, viral infections become very important, particularly CMV and other herpes viruses. The relative success in dealing with bacterial and, to some extent, viral infections has brought fungal infections to the fore as major causes of death, especially in higher risk categories of patients. Hemorrhage is a frequent complication owing to delayed megakaryocyte engraftment and thrombocytopenia during the early period and is a serious problem in patients with GVHD of the gut.
...
PMID:Pathology of bone marrow in transplant recipients. 306 26

We report on a 16 year old girl with relapsed Ki-1 lymphoma and a very poor prognosis. The initial manifestation was multiple bone metastases and lymphadenopathy. The patient achieved remission with modified adriamycin, bleomycin, vincristine, daunomycine therapy. However, 14 months after the completion of therapy, relapse occurred in a new cervical lymph node on the left side. After preparation with chemotherapy and total lymphoid irradiation (TLI) the patient underwent autologous bone marrow transplantation (A-BMT). Ki-1 lymphoma shows clinically diverse symptoms, but hematopoietic stem cell transplantation should be performed in relapsed cases. It may be effective to give TLI followed by A-BMT for patients such as ours who have lymph node involvement without bone marrow metastasis.
...
PMID:Successful autologous bone marrow transplant for relapsed Ki-1 lymphoma. 757 63


1 2 3 4 5 6 7 Next >>

---