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)

Twenty patients with advanced acute leukemia (16 acute myeloid leukemia (AML), three myeloid blast crisis (BC) of chronic myeloid leukemia (CML), one acute lymphatic leukemia) were treated with a peroral regimen consisting of etoposide 80 mg/m2 and 6-thioguanine 100 mg/m2 twice daily for 5 days, and idarubicin 15 mg/m2 once daily for 3 days (ETI). Two AML patients were in first relapse. All the other patients with acute leukemia had a later relapse or were refractory to primary or salvage treatment. One to six ETI cycles were given. Four AML patients achieved remission and one patient with BC of CML entered the second chronic phase. Clearing of the blood of leukemic cells was seen in seven additional patients. Infection was the most common complication, gastrointestinal toxicity was not a major problem. In conclusion, peroral ETI treatment has a marked antileukemic effect even in an advanced disease, and the toxicity is moderate and well acceptable.
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PMID:Etoposide, 6-thioguanine and idarubicin, an oral combination regimen (ETI) for the induction treatment of acute leukemia. 186 45

The BCR/ABL gene, formed by the Philadelphia chromosome translocation (Ph1) of human chronic myelogenous leukemia, encodes an altered ABL gene product, P210. P210 is strongly implicated in the malignant process of chronic myelogenous leukemia, but it precise role is unknown. Infection of long-term bone marrow cultures enriched for B-lymphoid cell types with a Moloney murine leukemia virus retroviral vector containing the BCR/ABL cDNA resulted in clonal outgrowths of immature B-lymphoid cells which expressed abundant P210 kinase activity. Surprisingly, infection of long-term myeloid lineage-enriched cultures also resulted in clonal outgrowths of immature B-lymphoid cells. The P210-expressing lymphoid cell lines resulting from either type of culture were resistant to the lethal effects of corticosteroids. These findings indicate that high levels of P210 expressed from a Moloney murine leukemia virus long terminal repeat preferentially stimulate the growth of immature B-lineage cells, and this effect is apparent even in myeloid lineage-enriched cultures, in which few if any lymphoid cells can be detected prior to infection.
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PMID:Selective transformation of primitive lymphoid cells by the BCR/ABL oncogene expressed in long-term lymphoid or myeloid cultures. 326 66

We studied the potential value of oral ofloxacin (200 mg twice daily) for selective decontamination and infection prevention in 40 granulocytopenic patients with acute leukemia, blast crisis of chronic myelogenous leukemia, hairy cell leukemia or severe aplastic anemia. The quality of selective decontamination was acceptable with rapid elimination of Enterobacteriaceae from the alimentary tract, only a slight decrease in concentrations of anaerobes in faeces, and a small number of newly acquired transient (twelve isolates in seven patients) or colonizing (six strains with 28 isolates in four patients) aerobic gram-negative rods and Staphylococcus aureus (one isolate) recovered from 672 surveillance cultures from faeces, oral washings and urine. Two of three patients colonized with ofloxacin-resistant Pseudomonas aeruginosa strains developed Pseudomonas infections. A total of twelve acquired infections was observed. Six were microbiologically documented infections, all caused by ofloxacin-resistant bacteria (two P. aeruginosa, two Staphylococcus epidermidis, one Aerococcus viridans, one Micrococcus sp.). Tolerance was acceptable with no serious side effects observed. Mean drug concentrations in serum and saliva were comparable to those determined in healthy volunteers and were found to be higher in saliva than in serum. We conclude that ofloxacin may be studied as an effective alternative to trimethoprim-sulfamethoxazole for selective decontamination and infection prevention in severely granulocytopenic patients. Careful monitoring of colonizing Pseudomonas spp. with decreased ofloxacin sensitivity, however, seems necessary.
Infection
PMID:Ofloxacin for prevention of bacterial infections in granulocytopenic patients. 348 58

Infection with varicella-zoster virus (VZV) occurred in 231 (16.6%) of 1,394 patients undergoing marrow transplantation in Seattle, Washington, between 1969 and 1982. The probability of VZV infection was 30% by one year after transplant. Eighty percent of infections occurred within the first nine months after transplant, and of these cases 45% had cutaneous or visceral dissemination. Twenty-three deaths were associated with VZV infection, all within the initial nine months after transplant. Postherpetic neuralgia, scarring, and bacterial superinfection were also significantly more frequent among patients with VZV in the first nine months after transplant (32%) than among patients with later infection (19%; P less than .05). By multivariate analysis, allogeneic transplant, acute or chronic graft-vs.-host disease, patient age between 10 and 29 years, diagnosis other than chronic myelogenous leukemia, and posttransplant use of antithymocyte globulin were each risk factors for VZV infection. Among infected patients, the only significant risk factor for VZV dissemination or death was acute graft-vs.-host disease (P less than .03 and P less than .0002, respectively.
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PMID:Infection with varicella-zoster virus after marrow transplantation. 390 82

During 59 periods of hospitalisation, 39 patients with either acute myeloid leukemia (22), acute lymphatic leukemia (9), acute undifferentiated leukemia (1), blastic crisis of chronic myeloid leukemia (6) or high-grade malignant non-Hodgkin lymphoma (1) were subjected to aggressive polychemotherapy after selective decontamination of the gut. The patients were given an amphotericin B suspension in a dosage of 1.2 g/day for two days, after which one tablet of trimethoprim/sulphamethoxazole (TMP/SMZ) (160 mg TMP and 800 mg SMZ) t.i.d. was added to prevent endogenous infections by gram-negative aerobic bacteria or moulds and to maintain the "colonisation resistance" endowed by the anaerobes. During 16 of the 59 periods of hospitalisation, no potentially pathogenic aerobic bacteria were isolated. TMP/SMZ-resistant Escherichia coli were the etiological agent of septicemia in two patients, and resistant Klebsiella pneumoniae and Pseudomonas aeruginosa in two other patients. These bacteria were cultured from the patients' fecal samples prior to the development of septicemia. We observed that long-term prophylaxis with TMP/SMZ modified the normal aspect of the fecal biotop culture, not only by suppressing the aerobic gram-negative bacteria, but also by allowing certain clostridia to appear. We differentiated 207 clostridia from the fecal samples of 29 patients and observed a predominance of TMP/SMZ-resistant Clostridium difficile, Clostridium innocuum and Clostridium clostridiiforme. C. difficile was also isolated from the blood culture of a neutropenic patient treated with TMP/SMZ and proved to be very toxic in the Verocell culture.
Infection
PMID:The "clostridial effect" of selective decontamination of the human gut with trimethoprim/sulphamethoxazole in neutropenic patients. 635 9

Ceftezole (CTZ) was administered to 20 patients with hematopoietic malignancy complicated with infections. These patients consisted of 7 cases of AML, 2 ALL, 2 AMMoL, 1 APL, 1 blast crisis of CML, 2 HD, and 5 NHL. In 13 cases, sites of infection were determined and causative organisms were identified. In other 7 cases, sites of infection or causative organisms were unknown. In the former 13 cases, pneumonia was demonstrated in 6 patients, tonsillitis in 4 patients, pyelonephritis in 2 patients and sepsis in 1 patient. Klebsiella was separated from 5 patients as the causative organisms, E. coli from 2 patients, E. coli and Pseudomonas aeruginosa from 1 patient, Pseudomonas cepacia from 1 patient, Streptococcus viridans from 2 patients, Proteus from 1 patient and Torulopsis from 1 patient. Gram-negative rods were separated from 10 of the 13 cases (77%) as the causative organisms. CTZ was administered intravenously in dose from 4 g to 16 g per day combined with other antibiotics (AMK, GM, DKB, TOB, SBPC, CBPC, LC, ST). The response rate in 12 cases of acute leukemia and in 7 cases of malignant lymphoma was 58% and 43%, respectively. Infections occurred in 4 patients with less than 100 neutrophil per mm3 did never favorably responded even with CTZ.
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PMID:[Treatment of infection in the patients wih hematopoietic malignancy with ceftezole (Falomesin) (author's transl)]. 721 16

Mutants and fusion products of the c-abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre-B-lymphoma induction in pristane-treated N-myc transgenic BALB/c mice. A-MuLV induced PCs in 21 of 25 mice with a mean post-pristane latency period of 46 +/- 9 days, compared to 134 +/- 25 days in controls exposed to pristane alone. delta XB, a mutant of type IV c-abl with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 +/- 7 days, indicating that gag sequences are not required for rapid PC induction. The delta XB delta Nar mutant that carried a large C-terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C-terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR-ABL fusion constructs encoding an 185-kDa protein as in acute leukemia, or a 210-kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane-induced PC development in the N-myc transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non-transgenic littermates developed a pre-B lymphoma after A-MuLV infection, and none of 10 normal littermates infected with delta XB virus developed a construct-carrying tumor. This result suggests that PC acceleration is due to co-operative interaction of the N-myc transgene and activated abl. Infection of N-myc transgenic bone marrow or spleen cells with A-MuLV in vitro led to the outgrowth of pre-B lymphomas after transplantation to pristane-treated BALB/c recipients. The lymphoma-inducing activity of A-MuLV depends on its high titer, since diluted A-MuLV or the lower-titered delta XB induced only PCs under the same conditions. The v-abl, delta XB and BCR-ABL-carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N-myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.
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PMID:Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice. 801 9

Blastic transformation of chronic myelogenous leukemia (CML) is characterized by the presence of nonrandom, secondary genetic abnormalities in the majority of Philadelphia1 clones, and loss of p53 tumor suppressor gene function is a consistent finding in 25-30% of CML blast crisis patients. To test whether the functional loss of p53 plays a direct role in the transition of chronic phase to blast crisis, bone marrow cells from p53+/+ or p53-/- mice were infected with a retrovirus carrying either the wild-type BCR/ABL or the inactive kinase-deficient mutant, and were assessed for colony-forming ability. Infection of p53-/- marrow cells with wild-type BCR/ABL, but not with the kinase-deficient mutant, enhanced formation of hematopoietic colonies and induced growth factor independence at high frequency, as compared with p53+/+ marrow cells. These effects were suppressed when p53-/- marrow cells were coinfected with BCR/ ABL and wild-type p53. p53-deficient BCR/ABL-infected marrow cells had a proliferative advantage, as reflected by an increase in the fraction of S+G2 phase cells and a decrease in the number of apoptotic cells. Immunophenotyping and morphological analysis revealed that BCR/ABL-positive p53-/- cells were much less differentiated than their BCR/ABL-positive p53+/+ counterparts. Injection of immunodeficient mice with BCR/ABL-positive p53-/- cells produced a transplantable, highly aggressive, poorly differentiated acute myelogenous leukemia. In marked contrast, the disease process in mice injected with BCR/ABL-positive p53+/+ marrow cells was characterized by cell infiltrates with a more differentiated phenotype and was significantly retarded, as indicated by a much longer survival of leukemic mice. Together, these findings directly demonstrate that loss of p53 function plays an important role in blast transformation in CML.
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PMID:Blastic transformation of p53-deficient bone marrow cells by p210bcr/abl tyrosine kinase. 891 57

We have shown that a deletion mutant form of Bcr [Bcr(64-413)] is a strong inhibitor of the tyrosine kinase of Bcr-Abl in vitro and also inhibits its oncogenic growth effects (Liu et al., Cancer Res., 56: 5120-5124, 1996). To determine the effects of this Bcr-Abl kinase inhibitor on chronic myelogenous leukemia (CML) cells, we cloned BCR(64-413) into a recombinant, replication-defective adenovirus to express useful quantities of Bcr(64-413) in a wide variety of cells in culture. Infection of Cos1 cells with plaque-purified virus at a multiplicity of infection of 20-40 induced high expression of Bcr(64-413) as detected by Western blotting. Infection of hematopoietic cells at modest multiplicities of infection (20-40) required special conditions involving shifting cycling cells to a nongrowing condition involving serum starvation and cell crowding. Under these conditions, both Bcr-Abl-positive and -negative hematopoietic cells can be efficiently infected by adenovirus, as demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of cells infected by beta-galactosidase (beta-GAL) adenovirus. We found that expression of Bcr(64-413) in Bcr-Abl-positive K562 and BV-173 cells, but not Bcr-Abl-negative SMS-SB cells, increased cell-cell clumping and inhibited cell growth. In contrast to the effects of the Bcr(64-413) adenovirus, the beta-GAL adenovirus, despite infecting both types of cells, did not block growth or increase cell-cell clumping of Bcr-Abl-positive and -negative hematopoietic cells. Expression of Bcr(64-413) protein in primary cultures of cells from CML patients with active disease interfered with cell growth, induced apoptosis (as measured by annexin staining), and increased cell-cell clumping, whereas the beta-GAL adenovirus and mock-infected cells lacked these effects. In contrast, normal marrow cells did not exhibit these effects on infection with Bcr(64-413) adenovirus. We conclude from these findings that Bcr(64-413) interferes with the oncogenic effects of Bcr-Abl and therefore has the potential for use in therapy of CML.
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PMID:Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death. 1119 51

A phase II clinical study was performed to evaluate the effectiveness and toxicity of cladribine (2-CdA) combined with mitoxantrone (CM regimen) in the treatment of chronic myeloid leukemia in blastic phase (CML BP). A total of 12 adult patients with CML BP were included in this study. 2-CdA was given at a dose 0.12 mg/kg in 2-hour iv infusion on days 1-5 and mitoxantrone 10 mg/m2 i.v. day 1. The cycles were repeated at 4 week intervals in most cases. Complete remission (CR) was defined as the presence of < 5% of blasts in a normo- or hypercellular bone marrow in addition to normal peripheral blood counts and with normal physical examination. A partial response (PR) required normal peripheral blood counts but 5 to 25% marrow blasts. Toxicity was assessed according to WHO criteria. The patients received 21 courses of CM (median 2, range 1-3). Of 12 patients only 2 (17%), achieved PR. Responses were observed in patients with myeloid BP, after 3 and 2 courses, respectively. Myelosuppression was the main toxicity. Four patients (33.3%) had grade 3 or 4 neutropenia and 3 (25%) had grade 3 or 4 thrombocytopenia. Infections occurred in 4 patients (33.3%) and 2 of them died of sepsis shortly after CM treatment. This preliminary results in a small group of patients suggest that CM programme has limited value in pre-treated patients with CML BP. However, this regimen may be used as palliation in the end stage of disease.
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PMID:Cladribine combined with mitoxantrone in the treatment of blastic phase of chronic myeloid leukemia. 1158 90


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