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)

Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara-C) 500 mg/m2 [intermediate dose] or 1000 mg/m2 [high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2 for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils < 0.5 x 10(9)/l) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p = 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC or CML, strengthening the need for alternate approaches to be defined.
 ...
PMID:Treatment of chronic myelogenous leukemia in blast crisis and in accelerated phase with high- or intermediate-dose cytosine arabinoside and amsacrine. 822 Jan 18

The CML 88 study was designed to evaluate the efficacy of maintenance therapy in a multicentric randomised protocol using IFN combined with low-dose Ara-C versus IFN alone, following an induction with IFN + HU. Between April 1988 and February 1991, 237 patients from 36 French Hematology Centres were entered in the study. Preliminary cytogenetic results show a slightly higher, although not statistically significant, proportion of major chromosomal responses, including complete cytogenetic remissions, in the IFN + Ara C arm.
 ...
PMID:A multicentric randomised study of alpha 2b interferon (IFN) and hydroxyurea (HU) with or without cytosine-arabinoside (Ara-c) in previously untreated patients with Ph+ chronic myelocytic leukemia (CML): preliminary cytogenetic results. 825 93

Thirty patients with chronic myeloid leukemia in chronic phase and less than 1 year from diagnosis were treated with a combination of interferon alfa-2a (IFN) 9 million units daily continuously and intermittent low-dose cytosine arabinoside (Ara-C) 20 mg/m2 daily for 21 days every 42 days. The leukemia was controlled initially with hydroxyurea prior to commencing IFN and Ara-C. The treatment was continued for at least 12 months after which time nonresponders were withdrawn from the trial and responders continued on IFN alone. The median duration of follow-up is 14 months (range 10-53 months). Hematological response was assessed by clinical and laboratory parameters and cytogenetic response was assessed by regular bone marrow chromosome analysis. A complete hematological response occurred in 28/30 patients (93%). A complete cytogenetic response (no detectable Philadelphia chromosome-positive metaphases) was present on at least one occasion in 9/30 (30%), a partial cytogenetic response (between 1 and 34% Philadelphia chromosome-positive metaphases) in 7/30 (23%) and a minor response in 4/30 (13%), giving an overall cytogenetic response rate of 67%. Significant side effects included mucositis, nausea, cytopenia and depression. Side effects could be managed by dose reduction or temporary cessation and were tolerable in most patients, but in 1 patient this led to withdrawal from the trial due to severe depression. Two patients have transformed, 1 to acute lymphoblastic leukemia and 1 to accelerated phase. Two patients have died after exiting the study, both from complications of allogeneic bone marrow transplantation. In conclusion, these results are superior to the results using IFN alone and indicate the need for a randomized study.
 ...
PMID:Combined interferon alfa-2a and cytosine arabinoside as first-line treatment for chronic myeloid leukemia. 847 67

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.
 ...
PMID:Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients. 854 29

Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108 investigations on 68 patients containing all three parameters: 12 on untreated patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after allogeneic BMT, five before and three after stem cell mobilization, and three after autologous stem cell transplantation (ASCT). In 53 cases (49%), cytogenetics and PCR gave identical results. In 40 cases (37%), PCR from single colonies gave additional information compared to cytogenetics (e.g., mosaic in colonies when all metaphases were positive or negative). Most interesting were the results of one patient after IFN, one patient after ASCT, and 10 patients after BMT (14 investigations = 13%), showing only Ph'-negative mitoses accompanied by a negative nested primer PCR from fresh blood/bone marrow but single bcr-abl-positive progenitor colonies. False-positive results could be widely excluded by repeated insertion of negative controls into the experiments. One explanation for these results could be that CML, progenitors survive in the patient's body by being inactive and not proliferating. These cells express no or very little RNA and bcr-abl is not detectable by reverse PCR. When stimulated ex vivo in a colony assay by external growth factors, cells proliferate and produce detectable amounts of hybrid mRNA. The value of these observations is not clear. A follow-up of the patients will show if such sleeping progenitors can be activated in vivo. Concluding our observations, we can say that in special cases (therapy follow-up, detection of minimal residual disease) it could be useful to perform a PCR analysis of single progenitors in parallel with the routine investigations.
 ...
PMID:Detection of bcr-abl mRNA in single progenitor colonies from patients with chronic myeloid leukemia by PCR: comparison with cytogenetics and PCR from uncultured cells. 854 60

Most cytostatic drugs exert their effect on cells in active cell cycle. To improve the effect of cytostatic drugs we have tried, prior to treatment in vitro, to recruit tumor cells from G0 with growth factors. Leukemic cells from the bone marrows of 26 patients with AML and CML in blast crisis were incubated with G-CSF, GM-CSF and IL-3 for 24 h prior to incubation with cytostatic drugs. The cells were incubated with mitoxantrone, etoposide or daunorubicin for 1 h, or with Ara-C continuously. Prior to treatment, 4 patients with AML received GM-CSF for 24 h, after which blast cells from bone marrow were incubated with cytostatic drugs. After incubation with the cytostatic drugs, cells were cultured in a suspension culture for 4 d. The drug effect was determined with a bioluminescence ATP method. Leukemic cells were significantly stimulated by all three cytokines compared to an untreated control. GM-CSF and IL-3 increased the amount of cells 3- to 4-fold and G-CSF increased the amount 3 times compared to untreated cells. G-CSF significantly enhanced the cytotoxic effect of daunorubicin, mitoxantrone, etoposide and Ara-C by 20-40%, which GM-CSF and IL-3 showed a significantly increased toxicity for Ara-C only. Although the cytokines induced a higher percentage of cells killed with the cytostatic drugs, proliferation of the remaining cells resulted in an increased total number of cells from 1.5 to 3 times compared to the unstimulated incubations. We conclude that cytokines induce a higher level of toxicity of cytostatic drugs on leukemic cells, but the increased proliferation of the remaining cells may offset the clinical benefit.
 ...
PMID:Effect of cytokines on the toxicity of cytostatic drugs on leukemic cells in vitro and in vivo. 859 80

A new sensitive method for the measurement of 1-beta-D-arabinofuranosyl-CTP (ara-CTP), an intracellular active metabolite of 1-beta-D-arabinofuranosylcytosine (ara-C), in human materials in vivo has been established. An acid-soluble fraction containing ara-CTP was extracted from blastic cells by ara-C treatment with trichloroacetic acid (final concentration, 0.3 M) neutralized with an equal volume of cold freon containing 0.5 M tri-n-octylamine. The ara-CTP fraction was separated from the acid -soluble fraction by high-performance liquid chromatography (TSK gel diethylaminoethyl-2 SW column) eluted with 0.05 M phosphate buffer (pH 6.9) and 20% acetonitrile. ara-CTP was lyophilized, dephosphorylated to ara-C by incubation with 10 units alkaline phosphatase for 12 h at 55 degrees C, and measured by RIA using anti-ara-C serum. Recovery through the whole procedure was 92%. In the human chronic myelogenous leukemia cell line K562, the intracellular ara-CTP levels produced when the cells were incubated with ara-c were assayed as above, and they showed a linear increase depending on Ara-C concentrations from 0.01 to 10 microns, demonstrating a very close correlation with the labeled ara CTP levels yielded by cells on incubation with radiolabeled ara-C (r2 = 0.99). The detection limit was 0.1 pmol/5 x 10(6) cells, and a sample amount of only 5 x 10(6) cells was enough for each assay. In the clinical applications, our method proved capable of detecting a wide concentration range of ara-CTP produced when patients were treated with ara-C or its derivatives from very low to intermediate doses. No radiolabeled drug was necessary. The method was very useful for in vivo pharmacodynamic studies of ara-C therapy.
 ...
PMID:A new sensitive method for determination of intracellular 1-beta-D-arabinofuranosylcytosine 5'-triphosphate content in human materials in vivo. 862 Apr 96

Thirty-one patients with either advanced AML (18) or blastic CML (13) were treated with an intensive timed sequential combination of VP-16 (100 mg/m2/day i.v., days 1-3 and 8-10), intermediate-dose Ara-C (500 mg/m2 i.v. over 1 h q 12 h, days 1-3 and 8-10) and carboplatin (150 mg/m2/day i.v. continuous infusion, days 1-3 and 8-10). CR rates were 9/18 (50%) for patients with AML and 9/13 (69%) for those with blastic CML, for an overall CR rate of 58%. Among patients with AML, CR rates for specific subgroups were: primary resistant disease 2/6; resistant relapse 1/5; second relapse 6/7. Ten patients were refractory to VAC and three (10%) died of complications during marrow hypoplasia. Median overall survival was 7 months, and median DFS of the 18 responders 4 months. The major toxicity was myelosuppression and infection. The VAC regimen has significant activity and acceptable toxicity in myelogenous leukemias. The very high response rate observed in blastic CML warrants further testing of carboplatin-based regimens in this poor-risk form of leukemia.
 ...
PMID:A phase II study of VP-16, intermediate-dose Ara-C and carboplatin (VAC) in advanced acute myelogenous leukemia and blastic chronic myelogenous leukemia. 865 69

Myeloablative treatment followed by lymphohaematopoietic reconstitution with stem cells from umbilical cord blood (UCB) can cure children with leukaemia. The clinical experience of UCB transplantation with HLA 2- and 3-antigen mismatched siblings is rather limited and there are no reports of such patient being given UCB significantly contaminated with maternal T lymphocytes. In this study, we report our experience in treating a child with chronic myeloid leukaemia in blast crisis who was transplanted using UCB cells from mismatched sibling donor containing a significant number of maternal T cells. The patient received 1.17 x 10(8) nucleated cells/kg after conditioning with Ara-C, busulphan, TBI and cyclophosphamide. GVHD prophylaxis was with cyclosporine and an anti-CD25 monoclonal antibody. Although engraftment was somewhat slow it was complete as documented by cytogenetic analysis and DNA studies. Results of minimal residual disease monitoring by RT-PCR for the hybrid BCR/ABL gene showed no evidence of leukaemic mRNA post-transplant. Acute GVHD, skin only, developed on day +14 but promptly responded to low-dose steroids. The technique used for UCB collection may have cell contamination found. In spite of these potential disadvantages: advanced disease, HLA antigen disparate donor and significant maternal T cell contamination, the transplant was successful and at a follow-up of 14 months the child is well with no evidence of chronic GVHD. Immune naivety of cord blood and lack of immunological reactivity of maternal T cells in this context may have played a significant role in the outcome of this case.
 ...
PMID:Haploidentical cord blood transplant contaminated with maternal T cells in a patient with advanced leukaemia. 873 18

A 44-year-old woman with Ph-positive CML was treated with TBI, splenic irradiation, Ara-C, and CY. She then received unmanipulated marrow cells from her HLA-identical brother. GVHD prophylaxis was FK506 and MTX. WBC counts reached 1000/microliter on day 28 when all metaphases of marrow cells showed 46XY. However, on day 42, 46XX was detected in two of 20 metaphases, and the percentage of cells with female karyotype subsequently increased. On day 519, all metaphases showed female karyotype. BCR-ABL mRNA and Philadelphia chromosome were never detected throughout her post-transplant course. Fluorescence in situ hybridization (FISH) revealed complete recovery of host-derived hematopoiesis in the bone marrow, however, mixed T cell chimerism in the peripheral blood. This suggests that the persistence of donor-derived T cells may prevent disease recurrence through graft-versus-leukemia effect. The patient remains in a molecular complete remission with host-derived hematopoiesis 749 days post-transplant.
 ...
PMID:Durable molecular remission in a patient with chronic myelogenous leukemia and host-derived hematopoiesis after allogeneic bone marrow transplantation. 889 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>