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 polymerase chain reaction (PCR) has become a standard method for highly sensitive detection of the bcr/abl rearrangement in patients with chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). The exquisite sensitivity of the PCR facilitates the detection of residual leukemic cells after chemotherapy or after bone marrow transplantation. However, the detection of minimal residual disease does not yield any information on the malignant potential of the bcr/abl-rearranged cells. Qualitative PCR is therefore of limited prognostic value in the monitoring of residual leukemia. We have adapted the PCR for quantitative evaluation of cells carrying the bcr/abl rearrangement and by means of two exemplary cases of CML patients after bone marrow transplantation and under treatment with alpha-interferon, respectively, we show that this new technique is suitable for the long term follow-up of the activity of the residual bcr/abl rearranged clone. Longitudinal monitoring of residual disease by the technique presented provides a novel tool for detection of incipient relapse at a very early stage.
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PMID:Monitoring of residual disease in chronic myelogenous leukemia by quantitative polymerase chain reaction. 160 87

Fifteen chronic myelocytic leukemia patients in durable complete cytogenetic conversion (CCC) under interferon therapy, were monitored every three to six months by bone marrow (BM) karyotypes and/or reverse-transcription polymerase chain reaction (RT-PCR) on peripheral blood (PB) leukocytes (by a nested primer approach using two rounds of amplification, 30 cycles each). Special care was taken to minimize the risk of contamination. The median time of follow-up after first CCC was 12 months (range, 6-30). Thirty five BM karyotypes were performed. Only three patients demonstrated the transient reappearance of a few Philadelphia-positive metaphases, while other patients remained in CCC. Forty five PB samples were studied by RT-PCR. In two patients, no BCR/ABL transcript could be detected in three consecutive samples. In the 13 other cases, RT-PCR was intermittently negative, indicating a level of residual leukemic cells close to the threshold of sensitivity of the technique.
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PMID:Complete cytogenetic conversion in chronic myelocytic leukemia patients undergoing interferon alpha therapy: follow-up with reverse polymerase chain reaction. 160 97

Conventional or alkylating treatment for chronic myeloid leukaemia has little impact on overall survival. Recent treatments, however, are encouraging. Alpha interferon may prolong the chronic phase in some patients, while allogeneic bone marrow transplantation is curative in over 50% of patients with HLA-compatible donors.
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PMID:Current trends in the management of chronic myeloid leukaemia. 161 98

Therapy with alpha-interferon (IFN alpha) can suppress the Ph1-positive hemopoiesis in a percentage of patients with chronic myelogenous leukemia (CML). We used IFN alpha to treat a 30-year-old CML patient, characterized by favourable prognostic signs (such as low leukocytosis, absence of splenomegaly and no increase in bone marrow blasts) at diagnosis, and obtained a complete remission, as evaluated by Southern blot and cytogenetic analysis, after one year of treatment. However, the polymerase chain reaction (PCR) revealed the persistence of a minimal residual disease. The IFN alpha therapy was stopped and the hematological status remained stable until eighteen months later, when a cytogenetic analysis revealed the appearance of a clone characterized by t(9;22) and trisomy 8, accounting for 30% of bone marrow metaphases. This cell population spontaneously regressed in the following months, before any cytotoxic treatment. However, as leukemic cells, detected by PCR, were still present, the patient received a high dose chemotherapy, which induced the complete eradication of the Ph1-positive clone, as demonstrated by the absence of bcr-abl transcript at the PCR reaction. Molecular and cytogenetic remission persist one year later, without any further therapy.
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PMID:Transient cytogenetic relapse in a Ph1-positive chronic myelogenous leukemia patient previously treated with alpha-interferon. 162 97

Suppression or eradication of the Philadelphia (Ph1) chromosome has been a major goal in the therapy of chronic myelogenous leukemia (CML). Variable levels of Ph1 chromosome negativity have been achieved using interferon-alfa, busulfan, combination chemotherapy, and allogeneic bone marrow transplantation. This study evaluated the effect of achieving a predetermined level of myelosuppression using hydroxyurea on bone marrow cytogenetics in CML. Fourteen patients with chronic phase CML received 25 cycles of therapy. Fourteen of the 25 cycles were associated with cytogenetic responses consisting of 25% or more Ph1 negative metaphases (range, 25% to 100%). Nine of the responses consisted of 50% or greater Ph1 negative metaphases. Toxicity was exclusively due to consequences of myelosuppression, including febrile neutropenia and thrombocytopenia. In chronic phase CML, hydroxyurea induces cytogenetic responses with tolerable toxicity and is an attractive agent for further study as a component of treatment strategies aimed at eradicating the Ph1 + population in CML.
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PMID:A phase II pilot trial of high-dose hydroxyurea in chronic myelogenous leukemia. 164 54

Fifteen patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who were ineligible for allogeneic bone marrow transplantation (BMT) or alpha-interferon therapy were included in this study. Eight patients were in the first late chronic phase, five were in the second chronic phase, one was in the accelerated phase, and one was in the blastic phase. Autologous bone marrow cells (median, 2.5 x 10(8) nucleated cells/kg) were stored at a median of 30 months after diagnosis. Patients were treated with cyclophosphamide (1.5 g/m2 daily for 4 days), carmustine (BCNU) (300 mg/m2), and etoposide (VP-16) (250 mg/m2 daily for 3 days) (CBV), followed by reinfusion of autologous bone marrow. Hematopoietic recovery was rapid, and toxicity was mild to moderate in 14 patients. One patient died of cytomegalovirus pneumonitis. Eight of 15 patients showed Ph suppression to less than 90% Ph-positive metaphases after autologous BMT. Major cytogenetic responses (Ph suppression to less than 35% Ph-positive metaphases) developed in four patients. Cytogenetic responses were observed in 4 of 11 patients infused with 100% Ph-positive marrows, and in all 4 patients infused with Ph-mosaic marrows (mixture of diploid and Ph-positive cells). Better results were observed when autologous BMT was performed in the chronic phase compared with the advanced phases. The major cytogenetic responses have lasted for 3, 4, 12, and 15+ months, whereas minor cytogenetic responses lasted for only a short time (less than 2 months). Three of seven patients (43%) in the chronic phase with previous resistance to alpha-interferon therapy became sensitive to alpha-interferon therapy after autologous BMT. The authors concluded that intensive chemotherapy followed by autologous BMT produced cytogenetic remissions in patients with Ph-positive CML and reinduced disease sensitivity to alpha-interferon therapy in patients previously resistant to it. This is particularly useful when treatment is given during the chronic phase and stem cells are collected at a time of previous cytogenetic remission.
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PMID:Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative cells in chronic myelogenous leukemia. 167 51

The success of bone marrow transplantation in chronic myelogenous leukemia (CML) is strongly associated with the phase of the disease at the time of transplantation. For allogeneic transplants from siblings with identical human leukocyte antigens, the 3-year survival rate for recipients in chronic phase ranges from 55% to 70%, whereas survival falls to approximately 30% for recipients in accelerated phase and to 0% to 20% for patients receiving transplants during blast crisis. Detailed analysis of data pooled from 405 patients demonstrated that the 3-year probability of relapse was 48% for recipients of T-cell-depleted bone marrow, but only 9% for recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than .0001). Regardless of transplant T-cell status, however, patients who developed chronic graft-versus-host disease (GVHD) were less likely to relapse at 4 years when compared with recipients without chronic GVHD (6% v 24%; relative risk, 3.1; P less than .01). Survival was correlated with severity of acute GVHD and age. Allogeneic bone marrow transplantation from unrelated donors can be useful in expanding the patient population eligible for transplantation. A study of recipients of transplants from unrelated donors showed a 3-year projected survival of 55% for chronic phase patients, and 22% for patients with advanced disease. However, a high rate of graft failure (10%) and grade II to IV acute GVHD can be expected. Preliminary data suggest that ex vivo treatment of autologous bone marrow with interferon can effect complete or partial Philadelphia (Ph) chromosome negative bone marrow mosaicism, although appearance of Ph chromosome negative metaphases may not be persistent. Thus, interferon treatment of autologous bone marrow may play a more significant role in the treatment of CML.
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PMID:Bone marrow transplants in chronic myelogenous leukemia: an overview of determinants of survival. 169 63

Interferons are proteins with antiviral, antiproliferative, and immune-regulating activity. They are classified as alfa, beta, or gamma on the basis of antigenicity and biologic properties. Alfa interferons as single-agent therapy produce clinical improvement in approximately 90 percent of patients with hairy-cell leukemia, and up to 70 percent of patients with chronic myelogenous leukemia (CML) in early-stage disease. Prolonged suppression or elimination of the leukemic cell clone by interferon may ultimately increase survival of patients with CML. Interferon is not effective single-agent therapy for multiple myeloma, but improves response rate when combined with conventional agents. AIDS-associated Kaposi's sarcoma demonstrates a 40 percent objective response rate to interferon, with less risk of immune system suppression than conventional cytotoxics. Other applications of alfa interferon include malignant melanoma and renal cell carcinoma. Beta interferon is similar to the alfa subtype and may have utility in treatment of brain tumors. Gamma interferon is an important immune regulator with qualitative and quantitative differences in its efficacy and toxicity when compared with alfa interferon.
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PMID:Clinical use of biologic response modifiers in cancer treatment: an overview. Part I. The interferons. 169 95

We have previously shown that maturing neoplastic cells from patients with stable phase chronic myelogenous leukemia (SP CML) constitutively produce granulocyte colony-stimulating factor (G-CSF) and are also receptive for this molecule. G-CSF functions as an endogenous growth factor in SP CML, and thus is responsible for divisions in maturing leukemic cells leading to an expansion of the compartment of mature cells. In the investigations to be reported below, the effects of various hematopoietic inhibitor molecules on the expression of the G-CSF gene by SP CML bone marrow cells enriched for promyelocytes/myelocytes were examined at the mRNA and protein level. We show that exposure of SP CML bone marrow promyelocytes/myelocytes to recombinant human (rh) interferon (IFN)-gamma but not to rh IFN-alpha, rh tumor necrosis factor (TNF)-alpha, and rh lymphotoxin (LT) leads to downregulation of G-CSF expression and interruption of the G-CSF-mediated endogenous growth stimulation. The action of G-CSF takes place at the posttranscriptional level and involves an acceleration of decay of steady-state levels of G-CSF transcripts in the malignant cell population.
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PMID:Gamma-interferon interrupts growth stimulation in chronic myelogenous leukemia established by endogenous granulocyte colony-stimulating factor. 170 Feb 39

alpha-Interferon induces hematological and cytogenetic remissions in some individuals with newly diagnosed Philadelphia-positive chronic myelogenous leukemia. However, interferon-resistant disease occurs in a consistent patient subset (primary resistance) and develops during therapy in additional patients (secondary resistance). Several alpha-interferon-inducible genes have been characterized. In interferon-resistant cell line variants, defects in these genes have been implicated in the mechanisms mediating resistance. We have, therefore, evaluated mRNA expression of four interferon-stimulated genes (ISGs) following alpha-interferon therapy. Twenty-seven chronic myelogenous leukemia patients (ten interferon-sensitive patients, 17 interferon-resistant patients) were studied. Peripheral blood samples were collected prior to and 1 to 7 days after starting interferon therapy and analyzed for the expression of 2'-5' oligoadenylate synthetase, ISG-15, ISG-54, and 6-16 transcripts. Following therapy with alpha-interferon, 2'-5' oligoadenylate synthetase, ISG-54, and 6-16 transcripts were discerned in all patients regardless of their response to interferon. The ISG-15 message was detected in eight of nine interferon-sensitive and in 15 of 16 interferon-resistant patients, as well. Overall, no consistent defect in the ISG system could be identified. Therefore, lack of induction of these genes cannot explain resistance to alpha-interferon in chronic myelogenous leukemia patients. Other mechanisms such as posttranslational modification, leading to defects in the ISG corresponding proteins, may play a role in the development of resistance.
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PMID:Interferon-stimulated genes in interferon-sensitive and -resistant chronic myelogenous leukemia patients. 173 66


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