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

An antigen with a molecular weight of 150 kilodaltons expressed on certain leukemia and lymphoma cells was recognized by a human monoclonal antibody (3H12), which had been established by the fusion of lymphocytes from a small cell lung cancer patient with a mouse myeloma cell line (P3U1). Peripheral blood mononuclear cells from 3 out of 4 cases with lymphoid crisis of chronic myelogenous leukemia (CML) were positively stained by 3H12, while cells from 5 cases with myeloid crisis of CML did not react to this antibody. The antibody did not show any reactivity to cells from the chronic phase of CML, other types of leukemias or normal hematopoietic cells. We further examined 29 cell lines of hematopoietic origin and found that 2 undifferentiated cells (BV-173 and K-562) reacted to the 3H12 antibody. In addition, we found that 3 out of 6 Burkitt lymphoma cells (DAUDI, RAJI and HR1K) reacted to 3H12. Taken together, these results suggest that the antigen recognized by 3H12 is a differentiation-associated antigen expressed on immature lymphoid cells, and could potentially be a reliable cell lineage marker.
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PMID:Human monoclonal antibody detects a cell surface antigen expressed on hematopoietic malignant cells of lymphoid lineage. 190 Aug 25

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.
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PMID:Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy. 191 38

Thirty patients with refractory lymphoid malignancies [multiple myeloma (MM): 8, plasma cell leukemia (PCL): 2, acute lymphocytic leukemia (ALL): 5, chronic myelogenous leukemia in blast crisis: 1, chronic lymphocytic leukemia in blast crisis: 1, adult T-cell leukemia: 1, non-Hodgkin lymphoma (NHL): 9, Hodgkin's disease (HD): 3] were treated with VAD regimen (vincristine, doxorubicin, dexamethasone). Of 28 evaluable patients, 4 patients achieved complete response or remission [MM1, ALL1, NHL1, HD1], 10 attained partial response or remission [MM5, PCL1, NHL3, HD1], and 2 patients with MM attained minor response. The remission duration ranged from 1 month to over 14 months. The response rate was high in patients with MM (75%) and lymphoma (60%), however 4 patients with T-cell malignancies achieved no response except one with NHL. In three patients who showed resistance to VAD, diltiazem was administered in addition to VAD and one patient with MM had response. Atrio-ventricular block was also observed in one patient during the period of diltiazem administration. Nine patients developed documented infections, 5 of which suffered from candida infections. From these observations, we concluded that VAD regimen might be useful as a salvage therapy especially in patients with MM and lymphoma.
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PMID:[The efficacy of VAD chemotherapy for refractory lymphoid malignancies]. 194 21

Ten patients with severe hematologic malignancies (four with acute leukemia, three with multiple myeloma, one with prolymphocytic leukemia, one with malignant lymphoma and one with blastic crisis of chronic myelogenous leukemia) developed respiratory failure during the period between April 1986 and May 1990. Clinically, the patients manifested high-fever, dyspnea refractory to oxygen therapy, diffuse pulmonary rales and severe hypoxemia without evidence of cardiogenic pulmonary edema. Chest roentgenograms displayed diffuse alveolar infiltrates. Respiratory failure occurred as early as 48 hours and as late as 66 days after the administration of intensive anti-neoplastic chemotherapy. At that time leukocyte count was between 100/microliters and 54,900/microliters. Marked leukocytosis was observed in two patients with AML and PLL. Respiratory failure was preceded by sepsis in one patient with AML and by pneumonia in nine patients. DIC was diagnosed in four patients. All patients treated with high dose methyl prednisolone (mPSL) within 12 hours after the onset of respiratory failure. Only one patient required assisted ventilation. High dose mPSL had significant effect on seven of ten patients. But three patients died from progressive respiratory failure, sepsis, pneumonia and multi-organ failure.
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PMID:[Clinical investigation on acute respiratory failure in patients with severe hematologic malignancy]. 194 22

Recently, several malignant cell types have been reported to express colony-stimulating factor-1 (CSF-1) transcripts; however, the clinical significance of CSF-1 in malignancy has not been investigated. Using a CSF-1 radioimmunoassay, we surveyed concentrations of biologically active CSF-1 in the peripheral blood of 316 patients with malignant and premalignant hematologic disorders; 75 had a myelodysplastic syndrome (MDS), 12 acute myelogenous leukemia (AML), 7 chronic myelogenous leukemia, 21 chronic lymphocytic leukemia (CLL), 106 non-Hodgkin's lymphoma (NHL; of low-, intermediate- and high-grade malignancy), 46 Hodgkin's disease (HD), 46 multiple myeloma (MM), and 3 monoclonal gammopathy of undetermined significance. Controls were 64 healthy subjects. The CSF-1 concentration was correlated with the type of disease, status of the disease, treatment status, and hematologic parameters. CSF-1 concentration was significantly elevated in 83.5% of the patients with active disease, and for each active disease group it was significantly greater (P less than .0001) than in the control. Thus, the high circulating CSF-1 concentration was not associated with a particular malignant phenotype or MDS subtype, but did correlate with the disease activity of both NHL and HD, and the tumor burden in MM, AML, and CLL. There was no correlation of the CSF-1 level with total counts of monocytes or neutrophils in patients with MDS or other malignancies. The cellular basis for the elevated circulating CSF-1 was not investigated. However, the results are consistent with the possibility that the premalignant or malignant cells themselves produce CSF-1 or regulate its production by normal cells.
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PMID:Increased circulating colony-stimulating factor-1 in patients with preleukemia, leukemia, and lymphoid malignancies. 201 2

Autologous bone marrow transplantation (ABMT) has developed considerably in the past 15 years and is now a routine procedure for the consolidation of acute leukemias, non-Hodgkin's lymphomas and Hodgkin's disease. In addition, ABMT has been tested in multiple myeloma (MM) and even considered in highly selected cases of chronic myelocytic leukemia (CML). Interest has resulted from the discovery of new purging procedures such as long-term cultures with or without serum-free media containing various lymphokines, the evaluation of cryoinjury on malignant cells, the increased detection of minimal residual disease using PCR, and the acceleration of hemopoietic recovery post-ABMT through the use of peripheral blood stem cells and/or lymphokines. Results presented include data from the international (ABMTR) and European (EBMT) registries, and our own unit in Paris. With respect to acute leukemias, (a) the EBMT listed 1,688 patients. The overall results were as follows: for patients autografted in complete remission (CR) 1, the leukemia-free survival and relapse rate at 7 years were 48 +/- 2% and 41 +/- 3% for AML and 44 +/- 5% and 45 +/- 5% in acute lymphoblastic leukemia (ALL), respectively. In CR2, the figures were 34 +/- 4% and 54 +/- 5% for AML and 32 +/- 3% and 62 +/- 4% for ALL, respectively. Patients not relapsing at 1 year post-ABMT had a probability of being cured at 7 years of 86 and 71% if autografted in CR1 and CR2 for AML and 81 and 59% for ALL, respectively. Multivariate analysis of relapse rates in several subpopulations confirmed the efficacy of marrow purging in AML CR1: in patients transplanted prior to January 1988 (minimum follow-up of 2 years), the relapse rate with purged marrow was 35 +/- 5% vs. 47 +/- 3% (p less than 0.005). (b) In Paris, St-Antoine, using TBI and marrow purged with mafosfamide at levels individually adjusted (Blood 1986;67:1367), the probability of remission and DFS were 84 and 62% in AML CR1 63 and 59% in ALL CR1, respectively. There was a statistically significant relationship between the relapse rate and the residual amount of CFUGM progenitors in the marrow after purging. The cutoff point was 0.3%, with a relapse rate of 54% in those receiving marrow containing the higher residual CFUGM fractions and only 29% in those receiving less. With respect to non-Hodgkin's lymphomas, the EBMT listed 698 patients. In intermediate or high grade lymphomas, the DFS at 6 years was 30% and 18% in sensitive and resistant relapses, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Autologous bone marrow transplantation in hematological malignancies. 204 65

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.
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PMID:A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies. 205 72

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.
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PMID:New drugs in the treatment of acute and chronic leukemia with some emphasis on m-AMSA. 206 23

Autologous bone marrow transplantation (BMT) has become effective therapy for high-risk hematologic leukemias with long-term disease-free survivals and apparent cure in a substantial fraction of patients with relapsed aggressive non-Hodgkin's lymphoma, relapsed Hodgkin's disease, and the acute leukemias. Preliminary reports suggest autologous BMT may also be useful treatment for low-grade non-Hodgkin's lymphomas, chronic myelogenous leukemia, and multiple myeloma. Recent studies have begun to address the role autologous BMT should play in these diseases, especially relative to conventional-dose therapy and allogeneic BMT. Relapse remains the major cause for failure following autologous BMT. Novel approaches that can increase the antitumor effect of this treatment without increasing toxicity are being investigated.
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PMID:Autologous bone marrow transplantation in hematologic malignancies. 206 87

Sialyl Lewisx-i (SLX) was found in more than 40% of patients with acute leukemia or chronic myelogenous leukemia, and in about 20% of those with myelodysplastic syndrome or malignant lymphoma. This tumor marker was absent in all patients with polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic lymphatic leukemia, multiple myeloma, and those with acute leukemia or malignant lymphoma in remission. The marker was found in 8% and of the patients with idiopathic thrombocytopenic purpura and 33% of those with autoimmune hemolytic anemia but in no patient with aplastic anemia or megaloblastic anemia. Immunostaining with SLX antibody showed that tumor cells of the patients with high levels of serum SLX were producing the SLX antigen. The detection of this marker in the serum is thought to be useful not only in the diagnosis but also in the observation of the recurrence of the diseases.
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PMID:Evaluation of serum sialyl Lewisx-i in hematologic disorders. 207 71


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