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)

DWA2114R (DWA) is a new derivative of platin compounds that is currently being used in Phase II studies of solid tumors in Japan. The dose-limiting factor is myelotoxicity with mild extramedullary toxicity. This Phase I study consisted of adult patients with relapsed hematologic malignancies. Eight patients received a total of 15 treatment courses of DWA. The starting dose was 800 mg/m2 over 24 hours by continuous infusion. The dose was first increased to 1200 mg/m2 and then to 1600 mg/m2. Clinical toxicity and urinary excretion studies of DWA suggested that 1200 mg/m2/d for successive days would be the best type of administration. When 1200 mg/m2/d was given for 5 days, Grade 2 to 3 diarrhea and nausea and vomiting were encountered requiring parenteral fluids and nutritional support. This suggested that the dose-limiting factor with this schedule was gastrointestinal toxicity. Myelotoxicity was severe, as expected, but tolerable. One of the five patients with acute nonlymphocytic leukemia (ANLL) entered into complete remission and one patient with chronic myelogenous leukemia (CML) in crisis returned to the chronic phase. A Phase II trial of DWA is warranted for hematologic malignancies, especially in myeloid diseases.
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PMID:A phase I study of a new cisplatin derivative for hematologic malignancies. 222 59

We studied the activity of serum adenosine deaminase (ADA) and its isozyme in 36 leukemic patients (16 ANLL, 11 ALL, and 9 CML) and 8 MDS. Isozyme was measured by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibitory assay. This assay was simple and reliable. The appearance rate of abnormally high ADA value were 81.24% for ANLL, 100% for ALL, 77.8% for CML and 37.5% for MDS. The ADA level became high when MDS turned into overt leukemia. In isozyme pattern, there was a clear difference between ANLL and ALL. The isozyme I/II ratio was significantly higher (p less than 0.001) in ALL than ANLL. Lymphoblastic crisis of CML also had a high isozyme I/II ratio. There was a correlation between isozyme I and absolute number of peripheral blasts in ALL (r = 0.768). When observed time sequentially, ADA and isozyme changed correlatively with the number of blasts counts. Serum ADA and its isozyme are useful parameters both for leukemic diagnosis and treatment.
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PMID:[Serum adenosine deaminase and its isozyme activity in leukemia and MDS]. 223 54

We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, -B, and -D antigens of the haplotype not shared; 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurrence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus" (A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of "one-locus"-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients.
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PMID:Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. 224 52

We present two cases in which translocations involving 21q22 were found at presentation in acute nonlymphocytic leukemia (ANLL). The first of these translocations, t(3;21)(q26-q27;q22), is previously unknown in ANLL, but appears indistinguishable from that reportedly associated with Philadelphia-positive chronic myelogenous leukemia. The second case involves t(15;21)(q21-q22;q22), a translocation previously undescribed in ANLL. Both of these exchanges involve 21q22 plus another chromosome region associated with leukemogenesis. We attempted to interrelate these cytogenetic data with the oncogenic significance of 21q22.
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PMID:Novel translocations in acute nonlymphocytic leukemia. Two cases involving chromosome 21, band q22. 229 84

The human multidrug-resistance gene (MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy.
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PMID:Expression of the multidrug resistance gene in myeloid leukemias. 230 54

The success of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) in complete remission (CR) is limited by the high relapse rate. It is generally accepted that minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute leukemia and in chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with mafosfamide (an in vitro derivative of cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of mafosfamide (80% DFS in 18 AL patients vs. 44% in 33 ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens, busulfan-cyclophosphamide is more effective in ANLL, and cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using mafosfamide marrow purging in CML demonstrate that the drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results.
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PMID:Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group. 230 82

Six-hour cultures of unstimulated peripheral blood cells from patients with various types of childhood leukemias were examined for chromosome karyotypes. It was found that this method was suitable for the detection of characteristic chromosomal abnormalities in two cases of acute nonlymphoblastic leukemias (ANLL; FAB types M3 and M6) and in a case of chronic myelogenous leukemia (CML), but not in acute lymphoblastic leukemias (ALL). The results suggest the usefulness of this simple method (possibly in combination with the thymidine boost technique of Yunis) in the cytogenetic diagnosis of some types of leukemias.
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PMID:Chromosome examinations on six-hour cultures of unstimulated peripheral blood from some patients with childhood leukemia. 231 88

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

We report on eight patients who were 35 to 77 years old with an isochromosome 17q as the sole structural chromosomal anomaly. Additional numerical chromosomal changes were a trisomy 8 or 17 in two cases each and a trisomy 19 in one case. Five patients had myelodysplastic syndrome (MDS) diagnosed according to the FAB nomenclature as chronic myelomonocytic leukemia (CMML) in two cases, refractory anemia with excess of blasts in transformation (RAEBt) in two cases, and refractory anemia with excess of blasts (RAEB) in one case. One patient suffered from a myeloproliferative disorder (MPS). All cases progressed to acute nonlymphocytic leukemia (ANLL) type M1, M2, or M4 in a period of 2 to 30 months after initial diagnosis, except one patient with RAEBt who died within 2 months. Two patients presented with ANLL-M2 at time of diagnosis. Treatment during the chronic phase of disease consisted of mild cytoreduction and/or substitution of platelets or red blood cells. One patient with CMML received an allogeneic bone marrow graft and relapsed after 33 months with ANLL-M1. Treatment results for overt leukemia were poor, and survival was short, lasting from 1 to 4 months. Overall survival was 1 to 37 months (median duration, 6.5 months). Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene, as observed in Ph1-positive chronic myeloid leukemia (CML). Thus, an i(17q) anomaly seems to identify a distinct subgroup of mostly myelodysplastic and, less frequently, myeloproliferative disorders that progress rapidly to ANLL, respond poorly to chemotherapy, and are associated with short survival after transformation.
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PMID:Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. 222 38

Mitoxantrone is a substituted anthraquinone with considerable activity against human acute leukemia. The authors' goal was to treat patients with continuous infusion mitoxantrone in order to maintain cytotoxic steady state levels with acceptable toxicity and to assess the results. Daily mitoxantrone levels showed a mean steady state plasma level of 16.8 +/- 1.4 ng/ml (range, 9.1-25.1) with a systemic clearance of 519 +/- 47 ml/minute/m2. No drug accumulation occurred. Mitoxantrone was undetectable 24 hours postinfusion. All patients, including two patients with chronic myelogenous leukemia in blast phase, had greater than 90% reduction in leukemia cell mass (marrow cellularity X percent leukemia cells) by day 6. However, six patients received 3 days of etoposide at that point because of residual acute nonlymphocytic leukemia (ANLL). Overall four patients (36%) had a complete remission; one additional patient had a bone marrow remission but also had a persistent granulocytic sarcoma. Toxicities included severe but tolerable myelosuppression, mucositis, and hepatic dysfunction. There was no correlation between mitoxantrone levels, toxicity, or clinical response. Continuous infusion produces cytotoxic plasma mitoxantrone levels and rapid clearing of ANLL from bone marrow. Further dose escalation may be possible.
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PMID:Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia. 234 Apr 63


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