Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy consecutive adult patients with acute myelogenous leukemia (AML), median age 44 years, received high-dose cytarabine (3 g/m2 every 12 hours for 12 doses) followed by daunorubicin (45 mg/m2 daily for three doses) for remission induction. A single, identical course was planned for postremission therapy. Complete remission (CR) was achieved in 63 patients (90%, 95% confidence interval [CI] 83% to 97%), 60 after a single course. Eight patients were selected to undergo elective bone marrow transplantation (BMT) during first CR. Of the remaining 55 patients, 40 (73%) underwent planned post-CR therapy; 15 patients did not, owing to early relapse, excessive toxicity from the induction chemotherapy, or refusal. Nineteen patients, including 13 who received planned post-CR therapy, remain in continuous CR at a median follow-up of 5.2 years (range 3.0 to 7.1 years). The 5-year actuarial leukemia-free survival was 30% (95% Cl, 19% to 42%) for all patients achieving CR and 32% (95% Cl, 19% to 47%) for the 40 patients who received the planned post-CR chemotherapy. Analysis of various putative prognostic factors for CR and overall and leukemia-free survival showed significance for a previous history of myelodysplasia, higher initial leukocyte counts, certain French-American-British (FAB) types, and certain abnormal karyotypes. None of these factors was consistently significant regarding the above parameters, although small patient numbers in certain analyses may have obscured significant associations. Myelosuppression was occasionally prolonged after remission induction and especially post-CR therapy. Severe cerebellar toxicity was observed in 13 patients; in 11 cases, this toxicity was fully reversible. Other serious complications were infrequent. Intensive chemotherapy with high-dose cytarabine and daunorubicin has substantial antileukemic activity in adult AML, and may represent an improvement over conventional therapy. Relapses were common, however, even in patients who received planned therapy, and substantial toxicity was observed. The optimum use of this regimen in AML remains to be determined.
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PMID:High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults. 200 67

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

377 untreated acute leukaemia patients were categorized according to FAB and cytochemical criterials and simultaneously phenotyped with the use of 6-21 monoclonal antibodies (MoAb) of VI series (W. Knapp, Vienna). The leukaemia phenotype was compared with the patients outcome after treatment. In adult ANLL patients a positive relationships was proved statistically between the expression of the CD 15 cell differentiation antigen on leukaemic blasts and the CR rate (p less than 0.01, chi 2 test). Also a comparison of the Kaplan-Meier survival curves revealed that the CD 15 positive group of ANLL patients has a better outcome than the CD 15 negative one (p less than 0.01, by Wilcoxon and Log-rank tests). Thus, examination of cell differentiation antigens could be a useful addition to existing risk assignment in acute leukaemia.
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PMID:The expression of CD 15 antigen on myeloid leukaemia cells--a new prognostic index for complete remission and for survival. 247 10

The concept of lineage fidelity in acute leukemia has recently been challenged by the finding of rearrangements of the immunoglobulin heavy chain genes in a leukemic cell line and in a small number of sporadic cases of acute nonlymphocytic leukemia with a monocytic phenotype. We therefore screened leukemic blood or bone marrow samples of 33 adult patients with acute nonlymphocytic leukemia of FAB types M4 (23 patients) and M5 (10 patients); 28 were obtained at diagnosis and 5 at relapse. All cases were well characterized pathologically and histochemically. Cytogenetic analysis performed in each case demonstrated karyotypes that were representative of those generally seen in these types of leukemia, with a clonal abnormality present in all except 9 of 32 patients who were successfully studied. DNA prepared from each sample was digested with the restriction enzyme BamH1 and analyzed by Southern blot hybridization to probes for the JH region of the immunoglobulin heavy chain. All 33 cases had DNA retained in the germline configuration with no evidence of rearrangement. This finding supports the concept of lineage fidelity, and suggests that true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in adult acute nonlymphocytic leukemia.
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PMID:Evidence favoring lineage fidelity in acute nonlymphocytic leukemia: absence of immunoglobulin gene rearrangements in FAB types M4 and M5. 309 29

Intraventricular chemotherapy was administered to adult AML patients via an Ommaya reservoir. Twenty-eight patients received central nervous system (CNS) prophylaxis and seven patients were treated for meningeal leukemia (ML). A treatment course lasted at least 6 months. Asymptomatic ML developed in two patients (7%) of the prophylaxis group concomitantly with bone marrow relapse. One of these patients had not completed the standard course. CNS remission could be obtained in all evaluable patients with ML. The easy entrance to the cerebrospinal fluid (CSF) offers the advantage of frequent investigations of the CSF, early diagnosis and treatment of CNS relapses without radiotherapy, and caused little patient discomfort. CNS prophylaxis in this small study seemed to prolong first remission duration slightly. In M4 and M5 subtypes CNS prophylaxis can be valuable.
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PMID:Experiences with the Ommaya reservoir for prophylaxis and treatment of the central nervous system in adult acute myelocytic leukemia. 320 92

Cytogenetic data from 30 children with acute non-lymphocytic leukemia (ANLL) are evaluated in connection with patient's age, morphological type of leukemia and prognosis. In 20 out of 30 patients clonal chromosome aberrations were found. The frequency of chromosome aberrations and the prognostic parameters in the various morphological and age groups proved to be different and no direct relationship could be found in a given group between the frequency of aberrations and the prognosis. A more detailed analysis of data, however, provided some evidence that chromosome aberrations observed at diagnosis had a prognostic value independent of age and the morphological properties of blast cells: the normal karyotype and the pseudodiploidy proved to be of a favorable value but the hyperdiploidy and polyploidy an unfavorable prognostic parameter. Besides the known cytogenetic differences between childhood and adult ANLL, some similarities are also emphasized.
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PMID:Cytogenetic investigations on children with acute non-lymphocytic leukemia. 338 59

Cigarette smoking has not been consistently associated with the subsequent development of leukemia. However, many of the earlier epidemiologic studies of leukemia have not considered specific histologic subtypes separately. The association between cigarette smoking and adult acute nonlymphocytic leukemia was examined in a case-control study of 114 patients and 133 controls. Cigarette smoking was associated with a significantly increased risk of acute myelocytic leukemia (relative risk estimate = 1.78, 95% confidence interval = 1.01 to 3.15) along with a significant (P less than 0.001) dose-response based on the total number of years of cigarette smoking. Since this is a preliminary study, more analyses of other epidemiologic studies are needed before it can be concluded that there is a causal association.
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PMID:Cigarette smoking and leukemia. 347 51

Ten cases of adult acute myeloid leukemia (AML) displaying lymphoid-associated markers CD7 and/or terminal deoxynucleotidyl transferase (TdT) have been investigated for rearrangement of immunoglobulin and T cell antigen receptor beta and gamma genes. Two of six TdT+ cases had clonally rearranged Ig genes, whereas six of eight CD7+ AMLs, including three that were TdT+, had a germ line configuration of both immunoglobulin and T cell receptor beta and gamma genes. A single case of CD7+ TdT- AML had clonal rearrangement of all three genes. These results indicate that expression of TdT and/or CD7 is not accompanied by gene rearrangement in most cases of adult AML. A minority of cases, displaying lymphoid-associated phenotypic markers and accompanying gene rearrangement, may represent a distinct subgroup of AML that arises from a rare, primitive stem cell, possessing extensive multilineage potential.
Leukemia 1987 Nov
PMID:Rearrangement of immunoglobulin and T cell antigen receptor genes in acute myeloid leukemia with lymphoid-associated markers. 350 Mar 72

High-dose cytosine arobinoside (HDAra-C) was originally introduced in clinical hematology for the treatment of refractory or relapsed acute leukemia. Recently, however, this treatment has been tried for remission induction and/or consolidation in early leukemia cases, and resulted in a fairly percentage of long-term survival cases. HDAra-C in combination with anthracyclines is now considered to be a treatment which may afford some hope of a cure in a certain percentage of cases of adult acute non-lymphocytic leukemia. This treatment also has the advantage of being an effective treatment for meningeal leukemia, since a high concentration of Ara-C effective enough to kill leukemic cells is maintained in the cerebrospinal fluid after intravenous infusion of high-dose Ara-C. In this paper, the HDAra-C treatment of acute leukemia is reviewed and the results of our group study on the treatment of 30 cases of refractory acute leukemia with HDAra-C are discussed.
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PMID:[High-dose Ara-C treatment of acute leukemia]. 370 45

Every adult acute nonlymphocytic leukemia patient in Rochester, New York seen from January 1975 to January 1982 was studied. Fifty percent of the patients did not receive combination chemotherapy. Among those who did, there was a significant selection bias toward placing patients with better prognostic features on protocol. Protocol patients were also treated with higher doses of chemotherapy than nonprotocol patients. However, these factors did not completely explain the significantly better complete response (CR) rate and survival among protocol patients. Eastern Cooperative Oncology Group (ECOG) participation remained an independent variable associated with a better outcome. An improvement in CR rate was seen during the 7-year period studied as compared to that seen between 1965 and 1974. The study provided evidence that the availability and use of ECOG protocols was a positive factor in the improvement of leukemia treatment in Rochester.
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PMID:Leukemia in Rochester (NY). A 17-year experience with an analysis of the role of cooperative group (ECOG) participation. 390 4


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