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 prognostic importance of pretreatment clinical and laboratory features was investigated in a group of 243 patients with Philadelphia chromosome positive chronic phase chronic myeloid leukemia from 1977-1995. Chemotherapy consisted of busulfan before 1993 or hydroxyurea after 1993. The overall median survival from diagnosis was 28 months. The mean age of the patients was 38 years, about 10 years below that of Western populations. Univariate analysis identified 4 poor prognostic features: thrombocytopenia, more than 5% peripheral blasts, more than 5% erythroid precursors and less than 7 g/dl of hemoglobin. The median survival times of patients with these 4 risk factors were 5, 11, 11 and 12 months respectively. Multivariate analysis only identified 2 significant prognostic features: thrombocytopenia and more than 5% peripheral blasts. Splenomegaly of more than 10 cm, basophilia and leukocytosis were associated with a shorter median survival but was not statistically significant. A risk scoring system was developed and used to classify patients into low, intermediate and high risk groups at 30.9%, 30.2% and 38.8% respectively. The median survival time according to the low, intermediate and high risk group was observed at 60, 27 and 14 months respectively. Prognostic factors for Thai patients with chronic myeloid leukemia have both similarities and differences with previously observed factors but the median patient survival time is shorter.
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PMID:Multivariate analysis of prognostic factors in Philadelphia chromosome positive chronic myeloid leukemia: an update of the first series in Thailand. 898 Jul 97

Hypermetaphase FISH (HMF), a molecular cytogenetic procedure combining the long term mitotic arrest of bone marrow cultures with detection of a specific chromosomal rearrangement by fluorescence in situ hybridization (FISH), has recently been shown to be effective in determining the frequency of Philadelphia chromosome positive (Ph+) cells in the bone marrow of chronic myelogenous leukemia (CML) patients undergoing treatment. By combining the probe for the Ph chromosome with one for the detection of the X chromosome, we used HMF to monitor the presence of malignant cells within the emerging host cell population in the marrow of a CML patient that had undergone sex-mismatched allogeneic bone marrow transplantation. In successive studies, we detected 0.5% and 1.75% Ph+ cells, respectively, confirmed by Western blot analysis for p210 protein. These readings occurred concordantly with a repopulation of host-derived diploid female cells. Standard G-band cytogenetic analyses did not detect any Ph+ cells at these time points. Intervention with donor lymphocyte infusion reinduced complete remission. This experience indicates that HMF is useful to identify low levels of repopulation by Ph+ cells in the marrow post-BMT at a stage when intervention is most efficacious.
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PMID:Usefulness of detection of minimal residual disease by 'hypermetaphase' fluorescent in situ hybridization after allogeneic BMT for chronic myelogenous leukemia. 908 36

We have used Southern blotting and fluorescence in situ hybridization (FISH) to define the breakpoints of a reciprocal translocation, t(10;12)(q24;p13), acquired as a secondary abnormality in a patient with Philadelphia chromosome positive chronic myeloid leukemia (CML) in transformation. A YAC clone that spanned the breakpoint at 12p13 was identified; this YAC included the CDKN1B gene but did not include ETV6. Neither ETV6 nor CDKN1B was rearranged, as determined by FISH and Southern blotting; however, a small deletion encompassing the translocated CDKN1B allele was detected. Analysis of two candidate genes at 10q24, HOX11 and NFKB2 suggested that they are not involved in this translocation. The preliminary mapping of breakpoints in this case demonstrated that they are different from an apparently identical translocation identified previously in a patient with myelodysplastic syndrome. The identification of the split YAC and small deletion should enable a more focused search for a gene or genes that may contribute to progression from chronic phase to blast crisis in CML.
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PMID:Characterization of a t(10;12)(q24;p13) in a case of CML in transformation. 940 58

Transformed chronic myeloid leukemia (CML) has a dismal prognosis, and treatment with a variety of chemotherapeutic agents is extremely disappointing. A novel therapeutic approach was initiated to improve the outcome of this condition. Nine patients, four females and five males, with either acceleration of CML or blast crisis (myeloid), or, in two instances, both, entered this pilot study. Median age was 60 years; seven patients were Philadelphia chromosome positive; two were negative but showed a bcr/abl rearrangement. All patients had a well-defined preceding period of stable chronic phase, for which they received sequentially hydroxyurea (N = 9), interferon (IFN) (N = 3), busulfan (N = 2), melphalan (N = 1), 6-MP (N = 1), or allogeneic BMT (N = 1). Median length of preceding chronic phase to acceleration or blast crisis was 56 months. All patients responded to treatment with a starting dose of IFN (9 Mio U/day), subcutaneously, and hydroxyurea (3 g/day), orally, by reversal to chronic phase. Three of the patients responded repeatedly during their course of disease. Median time for reversal to chronic phase was 4 weeks. Adverse side effects like nausea, vomiting, hair loss, fever, and prolonged cytopenia as seen after chemotherapy were not observed. The duration of chronic phase varied, and lasted, in six instances, more than 5 months, while the Philadelphia chromosome persisted. One additional patient received an unrelated bone marrow transplantation after reaching chronic phase (+24 months). Disease progression occurred 2 months after cessation of treatment. This treatment has proven very promising so far.
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PMID:Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon-alpha combined with hydroxyurea. 961 49

This study was a phase II evaluation of the activity of carboplatin in patients with Philadelphia chromosome positive accelerated or blastic phase of CML. Carboplatin, 250 mg/m2/day as an intravenous continuous infusion was given for 5 days, for a total dose of 1250 mg/m2 per course. If necessary, a second induction course could be given, and patients achieving complete remission were to receive an additional consolidation cycle at the same dose. Thirty-six patients were eligible and evaluable. There were five complete and three partial remissions for an overall response rate of 22% (95% CI 10.1-39.1%). The complete remission rate was 13.9% (95% CI 4.7-29.9%). The median remission duration was 3 months (range 1.4-8.94 months) and the median survival on study for all patients was 3.5 months (95% CI, 2.4-11.4 months). The median survival of responders was 12.8 months (95% CI, 3.6-17.2 months). Three eligible patients survived 2.0, 2.5 and 3.5 years following carboplatin therapy. Carboplatin has activity in blast crisis of CML, but responses are brief. Response did allow one patient to proceed to bone marrow transplantation and two other patients to continue therapy for chronic phase disease before returning to blast crisis. Activity in combination regimens should be explored.
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PMID:Phase II study of carboplatin in blast crisis of chronic myeloid leukemia: Eastern Cooperative Oncology Group Study E1992. 966 87

Patients with chronic myeloid leukemia (CML) relapsing in blast crisis after HLA-identical sibling bone marrow transplantation (BMT) are difficult to treat. Infusion of donor lymphocytes or retransplantation are unlikely to result in long-term disease-free survival. Treatment intensification with allogeneic double-BMT, made possible by using repeatedly mobilized peripheral blood stem cells, offers a new treatment option. We report two patients with Philadelphia chromosome positive CML transplanted in chronic phase, relapsing with CML in myeloid blast crisis. Both received intensive induction chemotherapy (ICE) followed by a first, T cell-depleted peripheral stem cell transplant from the initial donor. Both patients engrafted rapidly (day 15). Upon hematologic recovery, a second G-CSF mobilized non-T cell-depleted peripheral stem cell transplant from the same donor was given after pretransplant conditioning with busulphan and cyclophosphamide. Again, engraftment was rapid (days 18 and 16) and both patients are alive and disease-free 18 and 21 months after allogeneic double-BMT. G-CSF mobilized peripheral stem cells allow new ways of treatment intensification with double-BMT in refractory leukemias relapsing post-transplant. This approach warrants further study.
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PMID:Double allogeneic peripheral stem cell transplants for patients at high risk of relapse. 972 65

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.
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PMID:Expression patterns of costimulatory molecules on cells derived from human hematological malignancies. 989 58

Human p55, the major palmitoylated protein associated with the cytoplasmic face of the erythrocyte membrane, is believed to modulate interactions between protein 4.1 and glycophorin C. It is the prototype of a newly described family of signaling molecules that includes hD1g, the human homologue of the Drosophila discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized by transformation to a fulminating acute leukemia, heralded by evolution of the Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The deletion of constitutive exon 5 not only marks the first abnormality of the p55 cDNA in human disease but also the first abnormality of a PDZ domain in human disease and may represent another genetic abnormality associated with CML in blast crisis.
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PMID:Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis. 1007 Oct 76

A biomathematical model was developed to simulate relapse development in patients with chronic myeloid leukemia (CML) following bone marrow transplantation (BMT). The purpose of this study was to better understand the pathophysiology of the time evolution of CML relapse and to provide means whereby the outcomes of patients with CML relapse can be projected and treatment modified accordingly. The model consists of three parallel series of catenated compartments representing granulopoiesis in normal (donor) cells from the marrow, in CML cells from the marrow, and in CML cells from extramedullary sites. It was assumed that CML stem cells were resistant to feedback control and that CML-derived neutrophils, as well as normal neutrophils, exercised feedback regulation of normal stem cells. The known longer generation times for CML neutrophil precursors compared with normal neutrophil precursors were used, and it was assumed that 10(7) pluripotential stem cells were infused with BMT. The model was evaluated for its ability to simulate the reappearance of CML (Philadelphia chromosome positive) metaphases in the marrow and the recovery pattern in the blood neutrophil count in six patients who had relapsed following BMT (allogeneic in three patients, allogeneic with T-cell depletion in two patients, and syngeneic in one patient). The variables tested included the site of origin of the CML stem cells responsible for relapse (marrow alone versus marrow and extramedullary sites), the minimum number of CML stem cells responsible for relapse, and the time delay between BMT and the onset of relapse. Model profiles based on the observed values were obtained in each case. The simulations pointed to the fact that relapse began from a small number of CML cells in medullary and extramedullary sites. The time delay between BMT and the onset of relapse varied from 15 to 240 days. We suggest that this biomathematical model should be further investigated as a possible means of predicting outcome and guiding the treatment for patients with CML relapsing after BMT.
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PMID:Relapse in chronic myeloid leukemia after bone marrow transplantation: biomathematical modeling as a new approach to understanding pathogenesis. 1021 3

A case of a 70-year-old man who first developed multiple myeloma and then chronic myelogenous leukemia (CML) within a 3-year period is documented. The patient, with monoclonal hypergammopathy, was diagnosed with smoldering myeloma with IgG-kappa and Bence Jones protein kappa paraproteinemia. No chemotherapy was given for the myeloma until progressive leukocytosis developed after approximately 3 years. This was found to be due to Philadelphia chromosome positive CML. A reverse transcription-polymerase chain reaction assay did not reveal BCR/ABL mRNAs when the myeloma was first diagnosed. The occurrence of 2 distinct hematologic malignancies in the same patient suggests either a different clonal evolution from a common pluripotent malignant stem cell since the CML stem cell also involves the B-lymphoid lineage, a coincident complication of the 2 hematological malignancies, or the coexistence of 2 distinct malignancies due to the same genetic background and/or exposure to similar carcinogenic agents. The literature provides support for the existence of a relationship between multiple myelomas and CML.
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PMID:Multiple myeloma preceding the development of chronic myelogenous leukemia. 1049 53


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