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)

The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial.
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PMID:Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation. 142 80

Marrow transplant from an HLA-matched sibling donor can cure CML. Best results are observed when patients are transplanted early in chronic phase. T-lymphocyte depletion of donor marrow can effectively prevent chronic graft versus host disease, but is associated with a high incidence of relapse. Hematologic relapse after marrow transplantation can be treated successfully with alpha-interferon, donor buffy coat cells or second transplant. HLA phenotypically matched and, in some cases, 1 HLA antigen mismatched unrelated donors can also be used successfully for marrow transplantation therapy of CML. Complications include an increased incidence of graft failure and graft vs. host disease. Chronic phase patients transplanted early in the disease course have the best outcome. The development of the National Marrow Donor Program in the United States and a network of donor registries throughout the world as well as the establishment of new techniques for histocompatibility testing will increase the availability of unrelated donors and expedite the donor search process. Autologous marrow transplantation can induce complete hematologic and cytogenetic remissions and may prolong survival when compared with results expected from conventional therapy for CML. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection techniques and to develop further post-transplant anti-leukemia cell therapy to use as an adjunct to autologous marrow transplantation for CML.
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PMID:Unrelated donor and autologous marrow transplant therapy of chronic myelogenous leukemia (CML). 832 Oct 29

The chronic myeloproliferative disorders (MPD) comprise polycythemia vera (PV), idiopathic thrombocythemia (IT), chronic myeloid leukemia (CML) and myelofibrosis/osteomyelosclerosis (MF/OMS). Bone marrow biopsies of 3500 patients with known or suspected MPD were studied, and the clinical and morphologic variables registered were utilized for multivariate data analysis by selected BMD computer programs. The histologic criteria and the histologic subdivisions, as well as the evolution and prognosis of disease are outlined for each of the clinical entities. The results show that a bone marrow biopsy provides independent diagnostic and prognostic data in this group of hematologic malignancies and therefore constitutes an additional parameter in the diagnostic investigation of patients with suspected or established MPD.
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PMID:Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). 843 14

Chronic myelogenous leukemia is a lethal disease of the hematopoietic stem cell. Marrow transplant from an HLA-matched sibling donor can cure some patients with chronic myelogenous leukemia. Best results are observed when patients receive transplants early in chronic phase. The advantages of delaying marrow transplantation for a trial of interferon-alpha are questionable if a suitable matched related donor is available. The high incidence of relapse following T-lymphocyte-depleted marrow transplantation for chronic myelogenous leukemia emphasizes the existence of dormant, malignant clones that persist after ablative therapy. The presence of very small numbers of bcr-abl-positive hematopoietic cells after marrow transplantation can be detected by sensitive molecular genetic techniques and does not always predict hematologic relapse. Successful treatment of hematologic relapse after marrow transplantation can result from treatment with interferon-alpha, donor buffy coat cells, or second transplantation. HLA phenotypically matched and, in some cases, class I HLA antigen mismatched unrelated donors can be used successfully for marrow transplantation. Complications include an increased incidence of graft failure and graft-versus-host disease. Younger patients undergoing transplantation early in the disease course fare best. Preliminary results suggest that autologous marrow transplantation can induce complete hematologic and cytogenetic remission and may prolong survival in some cases. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection and to develop further posttransplantation antileukemic cell therapy to be used as an adjunct to autologous marrow transplantation for chronic myelogenous leukemia.
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PMID:Therapy for chronic myelogenous leukemia with marrow transplantation. 845 12

This study reviews results of a radiation-free preparative regimen consisting of busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients chronic phase, 13 patients accelerated phase, eight patients blast phase), 19 patients had acute leukemia (second complete remission or relapse) and eight patients had myelodysplasia. The patients were transplanted at four different medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median 32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120 mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients received cyclosporine for graft-versus-host disease prophylaxis; in addition 46 patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A-immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%. Four-year survival based on disease was 29 +/- 27% for chronic myelogenous leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40% for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66 +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and 10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft failure occurred in eight patients. Acute graft-versus-host disease grade II-IV occurred in 36 (72%). Two patients relapsed after engraftment with the donor cells and died of leukemia within a month of relapse. The most common causes of death were graft-versus-host disease (37%), and transplant-related toxicity (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an effective preparative regimen in unrelated bone marrow transplantation permitting adequate engraftment and a low relapse rate. Best results are observed in patients less than 20 years old.
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PMID:Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen. 873 82

In the majority of newly diagnosed patients with chronic myeloid leukaemia (CML), the bone marrow contains consistent numbers of normal Ph-negative surrogate stem cells (LTC-IC) which seem to decline rapidly with time. This is confirmed by mobilization studies showing that early after diagnosis is the optimal time to collect Ph-negative progenitor to be utilized for restoring Ph-negative haematopoiesis. In the marrow of the majority of CML patients at diagnosis Ph-positive LTC-IC are found at a lower frequency than Ph-negative LTC-IC and, unexpectedly, they do not show a tendency to increase with time as long as patients remain in chronic phase. Therefore, the decline of normal haematopoiesis does not seem related to a parallel increase in Ph-positive stem cells.
Baillieres Best Pract Res Clin Haematol
PMID:Normal and leukaemic haematopoiesis in bone marrow and peripheral blood of patients with chronic myeloid leukaemia. 1100 Sep 93

In chronic myeloid leukaemia (CML) allogeneic stem cell transplantation can be proposed to a minority of patients who are both less than 50 years of age and have an HLA-identical donor. Recombinant alpha-interferon induces cytogenetic responses (and prolongation of survival) in only 25-40% of patients. Thus, alternative treatments need to be proposed. When performed in chronic phase with unmodified stem cells, autologous stem cell transplantation is followed by cytogenetic responses in about 40% of cases, and some data suggest that these responder patients could have a prolongation of survival. This now needs to be demonstrated prospectively. If so, further studies could be performed in order to define the best source of stem cells (purged or unpurged) to be used.
Baillieres Best Pract Res Clin Haematol
PMID:Autologous peripheral blood stem cell transplantation for chronic myelocytic leukaemia, using unmanipulated grafts. 1100 Sep 92

The myeloproliferative disorders (MPDs) are a group of pre-leukaemic disorders characterized by proliferation of one or more lineages of the myelo-erythroid series. Unlike the Philadelphia chromosome in chronic myeloid leukaemia, there is no pathognomonic chromosomal abnormality associated with the MPDs. Chromosomal abnormalities are seen in 30-40% of patients with polycythaemia vera (PV) and idiopathic myelofibrosis (IMF) and seem to indicate a poor prognosis. On the other hand, chromosomal abnormalities are rare in essential thrombocythaemia. Consistent acquired changes seen at diagnosis include deletion of the long arm of chromosome 20, del(13q), trisomy 8 and 9 and duplication of parts of 1q. Furthermore del(20q), trisomy 8 and dupl(lq) all arise in multipotent progenitor cells. Molecular mapping of 20q deletions and, to some extent, 13q deletions has identified a number of candidate target genes, although no mutations have yet been found. Finally, translocations associated with the rare 8p11 myeloproliferative syndrome and other atypical myeloproliferative disorders have permitted the identification of a number of novel fusion proteins involving fibroblast growth factor receptor-1.
Best Pract Res Clin Haematol 2001 Sep
PMID:Myeloproliferative disorders. 1164 Aug 68

Allogeneic stem cell transplantation (SCT) has become the treatment of choice for some patients with haematological malignancies, allowing dose escalation of chemo-radiotherapy beyond the limits imposed by bone marrow toxicity. However, it is now apparent that dose escalation alone does not eradicate the malignancy in many cases and that an associated immune-mediated graft-versus-malignancy effect may be equally important. Its presence is supported by the following observations: anecdotal reports that patients with relapsed leukaemia following SCT may re-enter remission after withdrawal of immunosuppressive drugs; the lower risk of relapse associated with the development of graft-versus-host-disease (GVHD); and an increased risk of relapse in patients receiving syngeneic transplants or T-cell depleted allogeneic marrow grafts. More directly compelling evidence has been provided by the efficacy of donor lymphocyte infusions, particularly for relapsed chronic-phase CML. Issues that remain to be resolved include the precise nature of the effector cells and their target antigens, the best strategies for separating graft-versus-malignancy from GVHD, the role of adjuvant chemotherapy/cytokines, and the role of non-myeloablative transplantation.
Best Pract Res Clin Haematol 2001 Dec
PMID:Exploiting graft-versus-tumour responses using donor leukocyte infusions. 1192 18

This chapter describes the current role of unrelated donor stem cell transplantation (UD-SCT) in the management of leukaemia. The available data are scant and incomplete and there are few randomized studies comparing UD-SCT with alternative therapies. Patients with many of the leukaemias require prolonged follow-up after allogeneic SCT to determine whether they are cured; the registry-based comparisons that have been initiated reflect the results achievable some years ago and may not help us in deciding what is best in 2001. In addition, new therapies such as ST1571, even though the long-term outcome of patients treated with this agent is uncertain, may affect which patients with chronic myeloid leukaemia we decide to recommend for transplant. The focus here is on acute and chronic myeloid leukaemia, acute lymphoblastic leukaemia and chronic lymphocytic leukaemia, as well as the myelodysplastic syndromes. Patient selection, conditioning strategies, comparison with other therapies, timing of transplant and the major causes of treatment failure are discussed, and there is an exploration of where improvement will come from.
Best Pract Res Clin Haematol 2001 Dec
PMID:Allogeneic transplantation for leukaemia using unrelated donors. 1192 22


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