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)

We assessed pulmonary function and exercise tolerance in 10 BMT patients. Their underlying disorders were as follows; chronic myeloid leukemia 5 cases, acute lymphoblastic leukemia 2 cases, aplastic anemia, acute myeloid leukemia and non-Hodgkin's lymphoma one case each. Their mean age was 26 +/- 9 years old. When the patients were healthy and free of serious complications and anemia, arterial blood gas examination, pulmonary function tests and incremental treadmill exercise test were examined repeatedly. Although %VC and FEV1.0% kept within normal range, PaO2 at rest, %DLCO, VO2max, VO2max/kg and O2-pulsemax remained low at one year after BMT. There were significant correlations between VO2max and O2-pulsemax [r = 0.955 (p < 0.001)], %VC [r = 0.758 (p < 0.02)], VE/VO2max [r = -0.749 (p < 0.02)] and delta SaO2/VO2/kg [r = -0.731 (p < 0.02)], suggesting that exercise intolerance in BMT patients may be based on both cardiac and gas exchange abnormalities. To evaluate cardiac dysfunction, we compared exercise parameters obtained at an exercise level of 75% predicted heart rate max in five age-matched normal subjects to those in six BMT patients who did not demonstrate desaturation during exercise. As a result, the mean values of VO2max/kg and O2-pulse/m2 in BMT patients were significantly lower than those in normal subjects, suggesting that cardiac dysfunction may be due to insufficiency of stroke volume during exercise. It is concluded that exercise intolerance in BMT patients may be mainly due to cardiac dysfunction.
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PMID:[Pulmonary function and exercise tolerance in patients treated with bone marrow transplantation (BMT)]. 128 28

The human homologue of the SEA oncogene has been mapped recently to chromosome band 11q13. While studying the possible involvement of this gene in the variant translocation t(9;22;11) (q34;q11;q13) in a case of chronic myelogenous leukemia, we identified novel polymorphisms for XbaI and SacI restriction enzyme sites in the SEA gene. Frequency of the polymorphic alleles was studied in 100 samples from healthy controls, 94 samples from patients with non-Hodgkin's lymphoma, 25 samples from patients with benign lymphadenopathy, and 38 samples from patients with chronic myelogenous leukemia. XbaI digestion showed a three-allele polymorphism with two frequent alleles A (8.0 kb) and B (9.2 kb) and a rare allele (5.8 kb). After SacI digestion the probe identified two primary genotypes. Genotype I showed two hybridizable DNA fragments, one each of 6.6 and 3.5 kb. In genotype II the 3.5 kb fragment was absent, instead two smaller fragments, one each of 1.9 kb and 1.6 kb were present. The 6.6 kb fragment (allele AA) had three polymorphic sites generating 6.2 kb fragment (allele BB), 7.4 kb fragment (allele CC), and 7.8 kb fragment (allele DD). Frequencies of the two genotypes and the four alleles followed Mendelian proportions in all the samples studied. Furthermore, this study shows the importance of restriction map analysis of DNA in the vicinity of the probe of an oncogene to distinguish natural polymorphisms from the disease-related rearrangements in the gene.
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PMID:Novel restriction fragment length polymorphisms in the cellular oncogene SEA. 135 80

The cases of first-degree relatives from five families with hematological malignancies are described in this study. The occurrence of non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphoblastic leukemia (B-CLL) in the first family, NHL and chronic myeloid leukemia (CML) in the second one, two cases of Hodgkin's disease (HD) in the third and the fifth one's NHL and acute myelomonocytic leukemia (AMML) in the fourth one observed. Several factors which are considered to be involved in etiopathogenesis of hematological malignancies (virus infection, immune defects, HL-A antigens, cytogenic features) were discussed. Our study confirm other previous findings, that the familial susceptibility results from a combination of genetic and environmental influences.
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PMID:[Familial occurrence of malignant hematologic diseases]. 136 14

Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
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PMID:Expression of the Tn antigen in myelodysplasia, lymphoma, and leukemia. 147 Dec 47

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation. 154 48

We have assessed levels of surface-expressed complement regulatory proteins, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) on cells from patients with hematological malignancies. Neither malignant cells nor unaffected nucleated blood cells from the patients lacked MCP. On the other hand, complete deficiency of DAF was found in 2/10 of non-Hodgkin's lymphoma (NHL), while none of the 38 patients with acute nonlymphocytic leukemia (ANLL) (14 cases), chronic myelogenous leukemia (CML) (6 cases), acute lymphocytic leukemia (ALL) (12 cases) and chronic lymphocytic leukemia (CLL) (6 cases) lacked DAF. The two patients with DAF-negative NHL had no history of paroxysmal nocturnal hemoglobinuria (PNH), and their peripheral blood cells were DAF-positive. One DAF-negative NHL exhibited T cell markers and the other those of B cell. In both cases, treatment of the DAF-negative lymphoma cells with antibody against MCP (M177) followed by Mg(2+)-EGTA-serum resulted in efficient deposition of homologous C3. These results infer that some NHL specifically lack DAF and, through treatment with M177, are targeted by homologous C3.
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PMID:Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin's lymphoma. 172 75

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Between February 1988 and January 1990, 35 patients underwent allogeneic bone marrow transplantation (BMT) from unrelated donors using measures routinely employed for matched related donors. Median patient age was 34 years (range 2-49). Thirty-two patients had hematologic malignancies, including chronic myelogenous leukemia (CML) in 16; three patients had severe aplastic anemia. Donor-patient pairs were matched at the HLA loci tested serologically (HLA-A, -B, -DR) in 29 cases; mixed leukocyte culture results were variable but often reactive. Five patients died prior to day +28 without evidence of myeloid engraftment, and one patient developed fatal graft failure several months after initial engraftment. Acute graft-versus-host disease (GVHD) occurred in 77% (95% confidence interval [CI] 60-90%) of all patients, and GVHD contributed to the death of 10 patients. Fatal regimen-related toxicity occurred in four patients and another died due to neurologic complications of a process that resembled the hemolytic-uremic syndrome. Two acute leukemia patients relapsed, and a CML patient was found to have a localized non-Hodgkin's lymphoma at necropsy. As of 1 June 1991, 14 patients are alive and in remission at a median follow-up of 1.9 years (range 1.5-3.3); all except one have normal performance scores. The 2-year actuarial event-free survival for all patients is 40% (95% CI 24-56%). Proportional hazards analysis revealed favorable significance for female patient sex, less advanced disease status and shorter interval from diagnosis to BMT. While unrelated-donor transplants need not necessarily duplicate the results of related-donor transplants to be of benefit, the event-free survival in this series was roughly similar to that expected in the related-donor situation, with the high transplant-related mortality somewhat offset by a low recurrence rate. Further studies using unrelated donors, employing new methods of preventing transplant-related complications, are indicated.
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PMID:Allogeneic bone marrow transplantation using unrelated donors: a pilot study of the Canadian Bone Marrow Transplant Group. 179 Apr 28

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

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


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