Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-three patients with acute myelocytic leukemia (aml) were treated with daunomycin and the results contrasted to those obtained in a subsequent group of 18 patients treated with cytosine arabinoside (ara-c) and 6-thioguanine (tg). The complete remission (cr) rate with daunomycin was 17 percent (mean duration 10.6 months) and the partial remission (pr) rate 26 percent (mean duration 44 days). Corresponding figures in the ara-c and tg group were: cr rate 44 percent (mean duration 5.8 months) and pr rate 17 percent (mean duration 48 days). There were 12 deaths resulting from daunomycin-induced pancytopenia and in ten of the patients who died persistent leukemia infiltrate was found in antemortem marrow specimens or at autopsy. This contrasts with death of six patients from ara-c and tg-induced pancytopenia, in four of whom residual leukemic infiltrate was not evident. Daunomycin alone is deemed not suitable for induction of remission in aml. The results obtained with ara-c and tg are encouraging and may be improved if the number of infectious deaths associated with drug-induced pancytopenia can be reduced.
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PMID:Therapy of acute myelocytic leukemia. Daunomycin contrasted with a combination of cytosine arabinoside and 6-thioguanine. 450 67

We analysed the effects of three different regimens for first induction therapy with 50 cases of acute nonlymphocytic leukemia in adults and reported the results of combination therapy including aclacinomycin for reinduction therapy. Results obtained were as follows: The regimens of DCMP 2 step and Cc, P were superior to DCMP in remission rate (78%, 78% and 41%), median duration of CR (8.3 months, 5.0 months and 3.5 months) and survival time (6.5 months, 11.5 months and 2 months). Cc, P regimens obtained favorable CR rate in elderly patients over 50 years of age. (Cc, P: 100%, others: 40-50%) No significant difference in survival time was observed in patients who attained CR by three different regimens. In patients treated with combination therapy including aclacinomycin, the CR rate was 89% in the 9 previously treated patients (5 relapse cases and 4 refractory leukemias): All of these patients had previously been treated with DCMP 2 step or BHAC-DMP. Daunomycin (D), Cytosine Arabinoside (C), 6-Mercaptopurine (M) and Prednisolone (P) (DCMP), DCMP 2 step and Cyclocytidine (Cc) P.
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PMID:[Comparative evaluation of combined chemotherapeutic regimens in acute non-lymphocytic leukemia]. 619 91

To better define the frequency and clinical characteristics of herpes simplex virus (HSV) infection in adult patients with acute myelogenous leukemia (AML), the authors prospectively studied 29 patients undergoing remission induction chemotherapy with twice weekly throat wash cultures for an average of 25.3 days. Ten seropositive patients (34.5%) shed HSV at least once. Eight patients were asymptomatic. Two episodes of herpes labialis were severe and persistent, but no visceral dissemination was observed. Reactivation of HSV infections in AML patients presumably with marked immunosuppression occurs, but less frequently and more benignly than has been suggested. Daunomycin and cytosine arabinoside, which can inhibit HSV replication, may have accounted for this lower frequency of reactivation.
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PMID:Herpes simplex infection in acute myelogenous leukemia and other hematologic malignancies: a prospective study. 627 82

A 28-year-old man developed AML 18 months after a diagnosis of non-Hodgkin's lymphoma, diffuse small cell type, clinical stage IIA. Induction therapy for the lymphoma consisted 60Co 4000 rads bilaterally to the cervical areas and 2000 rads to the right cervical area. Complete remission was attained. Nineteen courses of combination chemotherapy with Vincristine (VCR), 6-meraptopurine (6 MP), cyclophosphamide (CY) and predonisolone (pred) was added (Total dose: VCR; 26.5 mg, 6 MP; 3320 mg, CY; 3350 mg, pred; 4310 mg). Seven days after the final chemotherapeutic treatment he developed AML with DIC. Leukemic cells were peroxidase and specific esterase (naphthol AS-D chloroacetate) positive. Induction therapy for the AML consisting of DCMP (Daunomycin, Cytosine arabinosid, 6 MP and pred) and VCR (vindesine, CY and pred) was unsuccessful. The patient died of cranial hemorrhage 3 month after the diagnosis of acute leukemia. Autopsy revealed no recurrence of non-Hodgkin's lymphoma in the lymph nodes, bone marrow, spleen and liver. Seven other cases reported in the Japanese literature are reviewed.
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PMID:[Post therapeutic myeloblastic leukemia in non-Hodgkin's lymphoma]. 659 32

The results of treatment of acute myeloblastic leukemia in patients over 60 years of age are evaluated in a retrospective study of 29 previously untreated patients. These results were very similar to those observed for younger patients, with 18 complete remissions (62, 1%), 6 early deaths, and 5 treatment failures. The median survival time was seven and one half months for all patients and 22 for the 18 patients achieving complete remissions. Nineteen patients received chemotherapy identical to that of younger patients (daunorubicin and cytarabine). The initial presence of poor prognostic factors (hyperleukocytosis, and infection) may explain the relativity high number of early deaths (21%). Elderly patients are apparently not exposed to a higher risk of death than younger patients. Daunorubicin toxicity does not appear to increase with age and this agent may therefore be used in the treatment of older patients.
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PMID:Acute myeloblastic leukemia in elderly patients: treatment and prognostic factors. 692 22

A human acute myelogenous leukemia cell line that forms colonies in soft-gel culture (KG-1) was used to test the effect of various schedules and combinations of chemotherapeutic agents. For comparison, the drug sensitivity of normal human marrow myeloid clonogenic cells was tested. Cytosine arabinoside inhibited both the KG-1 and normal human colony-forming cells (CFC) approximately 25% after a 2-hour exposure, 50% after a 5-hour exposure, and 90% after a 24-hour exposure. Daunorubicin had nearly an equal cytotoxic effect on KG-1 and normal marrow CFC after a 2- to 72-hour exposure to the drug. Daunorubicin at 0.15 micrograms/ml produced nearly complete inhibition of colony-forming cells. Amphotericin B also inhibited colony formation. Amphotericin B and daunorubicin, when combined in culture, produced a synergistic suppression of normal and leukemic CFC. The antileukemic agent 5-azacytidine at a concentration of 0.1 micrograms/ml produced approximately 60% inhibition of colony formation. Cytidine partially rescued CFC when the nucleoside was added in seven-fold excess to cultures containing 5-azacytidine. Leukemic and normal marrow clonogenic cells have nearly the same sensitivity to each chemotherapeutic agent and combination. Human acute myelogenous leukemia lines may provide useful models for the development of new chemotherapeutic schedules and combinations.
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PMID:An in vitro model for acute myelogenous leukemia chemotherapy. 694 1

The purpose of this study is to see if immunotherapy with C. parvum and prevention of central nervous system relapse with intrathecal methotrexate can prolong duration of complete remission and survival as well as avoid central nervous system relapse. For induction, three weekly I.V. injections of vincristine and Daunorubicin were given with daily prednisone orally, followed by 5-day courses of Cytosine Arabinoside and 6-mercaptopurine. The patients were randomized to chemotherapy or chemoimmunotherapy. Maintenance consisted of vincristine, Daunorubicin, and prednisone one week every odd month, and a 5-day course of Cytosine Arabinoside and 6-mercaptopurine every even month. Every week, the chemoimmunotherapy group also received, without chemotherapy, one injection of C. parvum 4 mg, subcutaneously. All patients received five weekly injections of intrathecal methotrexate 13 mg/m2 right after complete remission was achieved. Out of 181 evaluable cases, 80 (44%) achieved complete remission, 45 were randomized to chemotherapy, and 35 to chemoimmunotherapy. In the chemoimmunotherapy group 32/35 relapsed, and in the chemotherapy group 36/45. Median duration of complete remission and survival were: for group chemotherapy, 8 and 15 months; for group chemoimmunotherapy, 5 and 10 months. This difference is not significant. Intrathecal methotrexate was given to all patients. Six patients (7%) had central nervous system leukemia at the time of the first injection. None had central nervous system relapse after prevention with intrathecal methotrexate. This method seems useful in preventing central nervous system relapse in patients with acute myeloblastic leukemia, but does not seem to prolong complete remission.
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PMID:Chemoimmunotherapy with Corynebacterium parvum in acute myelocytic leukemia. 698 35

The effect of a synchronizing-recruiting drug schedule vs. myelotoxic therapy on remission rate and of Bacillus Calmette-Guerin on remission duration and survival of adults with acute myelogenous leukemia were studied in a prospective cooperative trial. After randomized remission induction with Arabinosyl Cytosine + vincristine + methotrexate + leucovorin (AVML), thioguanine + Ara-C + Daunorubin (TAD), or Daunorubicin + Ara-C (DA), complete remissions (CR) were consolidated with TAD or AVML. CRs were maintained with BCG vaccination (Tice strain) by the tine technique, or BCNU plus Ara-C (B/A), or no further therapy (NFT). Of 209 evaluable TAD patients, 105 (50%) achieved CR; of 187 DA, 97 (52%) achieved CR. AVML yielded only 15 CR among 59 patients (25%). The time to remission was significantly shorter with DA compared with TAD. Ninety-seven patients were randomized to maintenance therapy (35 B/A, 30 BCG, 32 NFT). There were no differences in remission duration (7, 8, 6 months) or survival (16, 22, 16 months, respectively). Manipulation of the cell cycle, as employed in this study, was not helpful. There may be a marginal effect of BCG, but our data fail to show a statistically significant benefit.
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PMID:Treatment of acute myelogenous leukemia: influence of three induction regimens and maintenance with chemotherapy or BCG immunotherapy. 703 13

In a panel of acute myeloblastic leukemia (AML) cell lines, representative of distinct differentiation stages, we investigated the possible correlation between drug-resistance and both expression and function of the multidrug resistance (MDR)-related P-glycoprotein (P-gp). The AML cell lines were KG1a, KG1, TF1, HEL, ML1, and two non drug-selected P-gp positive subclones originating from HL-60 (HL-60JD) and U937 (U937AQ). All these cells overexpressed the mdr1 gene (analyzed by RT-PCR) and displayed variable levels of P-gp expression. Flow cytometric semi-quantitative evaluation of P-gp with two P-gp specific monoclonal antibodies (MRK16 and UIC2) showed the following P-gp expression hierarchy: TF1 < KG1a < HEL < KG1 < HL-60JD < ML1 < U937AQ; the latter expressing 13 times more P-gp than TF1. When P-gp function was assessed by Rhodamine 123 (Rh123) efflux kinetics, we found that only KG1a and KG1 cells, which have an early (immature) CD34+ CD33- CD38- phenotype, and to a lesser extent TF1, with an intermediate (CD34+ CD33+ CD38+) phenotype, displayed significant P-gp activity which could be inhibited by both verapamil and SDZ PSC 833. In contrast, the other more mature CD33+ CD34- AML cell lines presented no Rh123 efflux capacity although they expressed higher P-gp levels. Daunorubicin (DNR) accumulation studies showed that inhibitors of P-gp increased DNR accumulation only in the immature AML cells whereas they had no impact on the mature AML cell lines. MTT drug cytotoxicity assay confirmed that the immature AML cells were 10-15-fold more resistant to DNR than the mature AML cells. Although P-gp inhibitors were able to increase the cytotoxicity of DNR in AML cells which displayed functional P-gp, they could not increase DNR cytotoxicity to levels comparable to that of the CD34- CD33+ cells, suggesting that DNR resistance of immature AML cells may not solely be related to P-gp. With drug-selection, AML subclones displayed higher levels of P-gp expression and higher extruding capacities, and therefore chemoresistance, and this independently of their initial differentiation phenotype. Finally, this study provides evidence for a lack of correlation between expression and function of P-gp in AML cells; this relationship being dependent upon leukemic cell differentiation in unselected myeloid leukemic cells.
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PMID:Lack of correlation between expression and function of P-glycoprotein in acute myeloid leukemia cell lines. 776 42

We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo acute myeloid leukemia (AML) at the initial diagnosis in order to further define the relationship between the presence of P-gp on leukemic cells and the efficacy of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, induction and survival. We found that 30 (60%) of the 50 patients were negative for P-gp expression (group 1) and 20 patients (40%) were positive (group 2) for P-gp expression by MRK16MoAb using a cut of 10% positive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2 (p < 0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p < 0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No significant difference has been achieved in group 1 terms of median duration of overall survival between DNR and IDR regimen; on the contrary the median duration of OS in patients of group 2 treated with IDR regimen was significantly longer than DNR regimen (p < 0.005). These results confirm the prognostic value of P-gp expression in AML at diagnosis and we suggest that Idarubicin could be a valid anthracycline drug for reversing multidrug resistance.
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PMID:Anthracycline drugs and MDR expression in human leukemia. 886 11


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