Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-eight patients aged 16-50 years with chronic myeloid leukaemia (CML) underwent allogeneic bone marrow transplantation (BMT) using human leukocyte antigen (HLA)-identical sibling donors. Of the 28 patients, 21 were in chronic phase, five were in accelerated phase and two were in blast phase at the time of BMT. Twenty-three of the patients survived more than 63-2187 days after BMT, 21 in continuous complete remission and two with haematologic relapse of CML. Two patients died of interstitial pneumonitis and one died of relapsed CML, cerebral aspergillosis and cytomegalovirus enterocolitis. The overall probability of survival at six years was 78% +/- 9% (mean +/- standard error) and of disease free survival 66 +/- 11%. For patients transplanted in chronic phase, the survival probability was 90 +/- 6%, while all of the patients undergoing BMT in chronic phase within the first year after diagnosis were alive with a relapse-free survival of 88 +/- 12%. The actuarial probability of occurrence of acute graft-versus-host disease (GVHD) was 57 +/- 9%, while for Grades II and III GVHD it was 28 +/- 9%. Chronic GVHD occurred in 18 of 25 patients at risk. The majority of patients had a Karnofsky performance score at latest follow-up of at least 90% (range 50-100). We conclude that allogeneic BMT is effective, curative therapy for CML and that BMT performed earlier in the natural history of the disease is associated with the best outcome.
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PMID:Chronic myeloid leukaemia treated by allogeneic bone marrow transplantation from histocompatible sibling donors--an invariably fatal malignancy rendered highly curable. 195 29

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.
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PMID:Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. 763 30

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus-leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.
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PMID:Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. 840 Feb 84

Donor lymphocyte infusions for treatment of relapse after allogeneic bone marrow or stem cell transplantation is being used with increasing frequency. Study of this form of adoptive immunotherapy will shed light on different aspects of cell-mediated cytotoxicity such as antigen presentation, processing, immune recognition, lymphocyte subsets involved, and mechanism of cell death. Donor lymphocyte infusions are extremely effective for cytogenetic relapses or chronic-phase relapses of chronic myelogenous leukemia, but are less effective in acute leukemias or other disorders. Donor lymphocyte infusions are associated with a significant risk of morbidity and mortality due to graft-versus-host disease and pancytopenia. Lower cell doses, earlier infusions, and selective depletion of CD8+ lymphocytes have been proposed as methods of diminishing these toxicities. Current research is focusing on methods of making donor lymphocyte infusions more effective in the nonchronic myelogenous leukemia setting, and decreasing their toxicity without losing their clinical efficacy in the treatment of relapsed chronic myelogenous leukemia.
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PMID:Donor lymphocyte infusions. 872 1

Relapse remains a significant problem after allogeneic bone marrow transplantation (BMT). For patients with relapsed chronic myelogenous leukemia (CML), infusions of donor mononuclear cells (MNC) provide a potent graft-versus-leukemia (GVL) reaction inducing complete remissions in the majority of patients. Little is known about the efficacy of donor MNC infusions for patients who relapse with other diseases. We have studied the GVL effects of donor MNC in eight patients with relapsed acute leukemia or myelodysplasia (MDS). One patient with relapsed MDS achieved complete remission and another patient had a transient response. Five of six non-responders died of progressive leukemia and one non-responder died of complications during second BMT. Three patients developed grade I-II acute GVHD responsive to immunosuppression. These data, and review of the literature, suggest that GVL induction with donor MNC infusions is less effective for patients with relapsed acute leukemia than for patients with relapsed CML; too few patients with relapsed MDS have been treated to draw definite conclusions. However, some patients respond, and given the high mortality associated with alternative procedures such as second BMT, donor MNC infusions are a reasonable approach for relapsed acute leukemia and MDS after allogeneic BMT.
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PMID:Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. 893 54

The clinical efficacy of donor lymphocyte infusions (DLI) in patients with relapsed chronic myelocytic leukemia after allogeneic bone marrow transplantation has been demonstrated in several recent studies. Although it is presumed that allogeneic T cells mediate this graft-versus-leukemia (GVL) effect, the influence of DLI on the T cell compartment of recipients has not been determined. To characterize the immunologic effects of DLI and to identify T cell changes selectively associated with the GVL response, we analyzed the T cell receptor (TCR) repertoire in four patients with relapsed chronic myelocytic leukemia who achieved a complete remission after infusion of CD4+ lymphocytes from HLA-identical sibling donors. Only one of the four patients developed clinically significant graft-versus-host disease (GVHD) after infusion of donor lymphocytes. TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies in serial samples obtained over a 1-yr period before and after DLI. Results were compared to 10 normal donors. Before DLI, all four patients were found to have abnormal TCR Vbeta repertoire in peripheral T cells, associated with a large number of clonal and oligoclonal patterns. Abnormal TCR patterns persisted for at least 3 mo after DLI, but thereafter gradually began to normalize. By 1 yr after DLI, all patients demonstrated almost complete normalization of Vbeta repertoire with polyclonal representation within almost all Vbeta gene subfamilies. We also examined changes in the TCR Vbeta repertoire associated with the disappearance of Ph+ cells. In each patient, we were able to identify the expansion of at least 1 Vbeta gene subfamily that coincided with the time of the cytogenetic response. In one patient who was studied in greater detail, CDR3 size analysis of serial samples after DLI indicated that these changes were associated with the appearance of clonal T cells. This finding was confirmed through CDR3 sequence analysis and use of CDR3 clone-specific oligonucleotide probes. A putative GVL clone identified by this technique was not detectable in either donor or patient T cells before DLI, but persisted in peripheral T cells for approximately 1 yr. These experiments therefore provide evidence for the clonal expansion of allogeneic T cells that may be selective mediators of antileukemia activity without also mediating graft-versus-host disease.
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PMID:Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion. 925 85

Eight patients with relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with alpha-interferon and leukocyte transfusions of the bone marrow donor. Six patients responded with disappearance of leukemic cells (Ph1, BCR-ABL) and reestablished donor hemopoiesis. All six patients developed bone marrow hypoplasia and graft-versus-host disease (GvHD). Three of the six patients died of cerebral bleeding, infection and GvHD, respectively. The remaining three patients are alive and well at day 418, 677, 818 after leukocyte transfusions. Two patients relapsed with more advanced disease of CML after BMT and failed treatment. Donor leukocyte transfusions provide an effective therapy for patients with relapsed CML after BMT, but are associated with a high mortality due to bone marrow hypoplasia and GvHD.
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PMID:[Leukocyte transfusion as therapy of recurrent CML after allogenic bone marrow transplantation]. 948 Jan 8

Until recently, the only curative therapy for patients with chronic myelogenous leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) has been second allogeneic BMT. Recently, donor mononuclear cells have been given to patients with relapsed CML to induce a potent graft-versus-leukemia reaction and re-establish complete remissions in the majority of patients without the need for a second transplant. The extraordinary success of donor mononuclear cell infusions shows that it is possible to manipulate and harness the graft-versus-leukemia (GVL) reaction for clinical benefit. The identity of the effector cells and target antigens is unclear, but intensive investigation is beginning to define the complex cytokine and cellular interactions that mediate GVL reactivity. Current clinical trials are investigating strategies that will retain and enhance the GVL effects while limiting toxicity from this therapy. Ultimately, the ability to harness the GVL potential of allogeneic donor cells without excessive toxicity from graft-versus-host disease will be a central challenge in BMT and cellular immunotherapy.
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PMID:Infusion of donor peripheral blood mononuclear cells to treat relapse after transplantation for chronic myelogenous leukemia. 952 29

Donor leukocyte infusions (DLI) from the original marrow donor have been shown to induce remission in patients with relapse after BMT. We analyzed factors that were associated with remission. Twenty-six patients with a relapse after T cell depleted BMT received DLI. The following pre-DLI factors were analyzed: sex and age of the patients and donors, GVHD after BMT, indication for DLI, percentage of donor T lymphocytes in the patient at the time of DLI, interval between relapse and DLI, and number of T lymphocytes infused. Remission was achieved in 11 of 15 patients (73%) treated for relapsed CML and in one of 11 patients (9%) treated for relapsed AML, ALL or RAEB-t (P = .002). Two of 13 patients (15%) with < or =40% of T lymphocytes from donor origin attained remission compared with 10 of 13 patients (77%) with >40% (P = .002). Two of 13 patients (15%) with an interval of < or =18 months between BMT and first DLI entered remission compared with 10 of 13 patients (77%) with an interval of >18 months (P = .002). Multivariate analysis demonstrated that indication for DLI (CML versus AML/ALL and RAEB-t) and the percentage T lymphocytes from donor origin (< or =40 versus >40) were significantly correlated with remission (P = .03). The occurrence of GVHD post DLI was highly associated with achievement of remission (P = .0001). DLI res ults in remission in a high percentage of patients with relapsed CML after BMT. The percentage of T lymphocytes from donor origin still present in the patient at the time of DLI is highly correlated with achievement of remission.
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PMID:In relapsed patients after lymphocyte depleted bone marrow transplantation the percentage of donor T lymphocytes correlates well with the outcome of donor leukocyte infusion. 1003 29

Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcr-abl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs. 45% and 45% vs. 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions.
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PMID:Interferon alpha for chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation. 1010 May 63


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