Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the in vitro effects of lymphokine-activated killer (LAK) cells from the peripheral blood of chronic myeloid leukemia (CML) patients after allogeneic and syngeneic bone marrow transplantation (BMT). LAK cells were generated by incubating peripheral blood mononuclear cells from patients post-BMT with recombinant interleukin-2 (IL-2) (500 U/mL) in 10% AB serum for 7 days. They were phenotyped and tested for activity in a standard 4-hour 51Cr release assay (n = 37) and in a CFU-GM assay (n = 24). We found that the LAK cells were mainly activated natural killer cells, but some were CD3+ T cells. In the 51Cr release assay LAK cells from 20 of 33 (61%) allogeneic and 2 of 4 syngeneic recipients killed recipient CML cells and in 22 of 37 (60%) cases also killed the HLA disparate CML cells. In the CFU-GM assay the LAK cells incubated together with the CML cells in liquid culture before plating inhibited (P less than .05) colony growth in 16 of 22 allogeneic and 2 of 2 syngeneic recipients. Cell-cell contact was necessary for optimal effect. There was little or no inhibition of proliferation of donor marrow CFU-GM. This in vitro graft-versus-leukemia (GVL) effect could also be demonstrated after LAK effectors were depleted of CD3+ T cells. It was inducible in recipients of both T cell-depleted and T cell-replete donor marrow and in recipients with or without graft-versus-host disease. These results suggest that a major histocompatibility complex-unrestricted GVL effect is inducible following allogeneic and syngeneic BMT. The use of IL-2/LAK cells after BMT could reduce the risk of relapse.
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PMID:Induction of in vitro graft-versus-leukemia activity following bone marrow transplantation for chronic myeloid leukemia. 224 25

We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, -B, and -D antigens of the haplotype not shared; 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurrence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus" (A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of "one-locus"-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients.
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PMID:Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. 224 52

The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute non-lymphoblastic leukemia in first complete remission (CR), the disease-free survival (DFS) is 45%, with a risk of relapse (RR) of 15%; in ALL in first CR the DFS is 60% with a RR of 15%; in ALL in second CR the DFS in 40%, with a RR of 30%; in CML in chronic phase the DFS is 60%, with a RR of 20%. These results have to be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GVH. The use of donors different from a genotypically matched related donor is currently under investigation. Mismatched related transplants give disappointing results except in the case of one HLA mismatch. Unrelated HLA matched donor panels have been recently established in various countries with 200 transplants performed with a DFS of approximately 40%. Current research tries to reduce the risk of relapse by intensifying the conditioning or using the GVL effect of allogeneic T cells, to reduce GVH by the use of monoclonal antibodies and to improve the engraftment by the use of growth factors.
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PMID:Recent trends in allogeneic bone marrow transplantation. 225 66

To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non--T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non--T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non--T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01), and both acute and chronic GVDH (relative risk 0.33, P = .0001) as compared with recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001) than recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.
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PMID:Graft-versus-leukemia reactions after bone marrow transplantation. 229 67

We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.
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PMID:Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors. 230 Jan 20

Examples are presented in which normal as well as abnormal chromosome distributions could be obtained from the same individual by means of bivariate flow karyotyping. Selective stimulation of T-lymphocytes obtained by E-rosetting from the blood of a patient with acute myelocytic leukemia resulted in a normal flow karyogram. The specific stimulation of myelocytic leukemia cells with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) yielded flow karyograms displaying the leukemia-associated chromosome abnormalities. The resulting flow karyograms could be used to discriminate between homolog differences, which appear normally in virtually every individual, and leukemia-associated chromosomal aberrations. In the case of a female chronic myelocytic leukemia patient who received bone marrow form an HLA-identical male donor, specific stimulation of various subsets of cells enabled to discriminate between leukemic host cells and non-leukemic donor cells. Both the leukemia-specific translocations and sex chromosomes were used as markers to analyse the flow karyograms obtained from the same sample.
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PMID:Clinical applications of flow karyotyping in myelocytic leukemia by stimulation of different subpopulations of cells in blood or bone marrow samples. 230 58

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.
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PMID:Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation. 231 Aug 31

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ("matched"). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ("mismatched"). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. 232 22

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analyzed. The median follow-up time was 48 months. One hundred and seventy patients were in 1st chronic phase, 111 were in more advanced disease. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse was correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic GVHD. The probability of disease free survival was significantly better for the patients who received a non T cell depleted marrow than for recipients of T cell depleted marrow. Bone marrow transplantion in first chronic phase with an HLA identical non T cell depleted marrow offers the better chance of prolonged leukemia free survival.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia. Results of the French Cooperative Group (GEGMO). 234 85


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