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)

We carried out an in vitro study on the combined effects of three CSF (G-CSF, GM-CSF and IL-3) plus the cycle-specific chemotherapeutic drugs [cytosine arabinoside (Ara-C) and daunorubicin (DNR)] on the proliferation and cytotoxicity of blasts and clonogenic cells (CFU-AML) in the AML-193 cell line, in AML patients and in normal bone marrow CFU-GM. The number of surviving blasts and/or DNA synthesis in blasts treated with CSF plus Ara-C or DNR was greater than those treated without CSF in the AML-193 cell line, and in some AML patients. On the other hand, the Ara-C- and DNR-mediated cytotoxicity of CFU-AML was not abrogated by CSF in any instance, but rather, it was significantly enhanced by all the CSF in the majority of instances. Although the enhancement was clearer when Ara-C was used, compared with DNR, there were no significant differences among the enhancing effects of the CSF. Under the same culture conditions as those for CFU-AML, all of the CSF significantly enhanced the Ara-C-mediated cytotoxicity of day 7 normal CFU-GM, although to a lesser extent than in CFU-AML. However, none of the CSF significantly affected the Ara-C-mediated cytotoxicity of day 14 normal CFU-GM or the DNR-mediated cytotoxicity of day 7 or day 14 normal CFU-GM. These results suggest that in the selection of a strategy entailing combined use of cycle-specific drugs plus CSF to increase the antileukemic effectiveness of chemotherapy in AML, G-CSF is preferable to GM-CSF or IL-3, since it has fewer potential clinical side effects, and that, furthermore, DNR may be as useful as Ara-C.
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PMID:Comparative effects of G-CSF, GM-CSF and IL-3 on cytosine arabinoside- and daunorubicin-mediated cytotoxicity of acute myeloid leukemia cells and normal myeloid progenitors. 139 3

To determine whether the biological characteristics of leukemic cells change after repeated chemotherapy, we compared the proliferative activity and drug sensitivity of leukemic blast progenitors in 7 patients with acute myeloblastic leukemia at diagnosis and in relapse. The proliferative activity of leukemic blast progenitors was assessed based on primary (PE1) and secondary (PE2) colony formation in methylcellulose culture and on the recovery of clonogenic cells in suspension culture. The effect of cytosine arabinoside (Ara-C) on leukemic blast progenitors was studied both in methylcellulose and in suspension cultures. PE1 and PE2 values varied among the patients. PE2 of 4 patients out of 7 patients became significantly higher in relapse than at diagnosis. The sensitivity to Ara-C of leukemic blast progenitors deteriorated in 5 patients in relapse. The results suggest that the biological nature in terms of proliferative activity and Ara-C sensitivity of leukemic blast progenitors may change in the clinical course after chemotherapy.
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PMID:Comparison of the proliferative activity and sensitivity to cytosine arabinoside of leukemic blast progenitors in acute myeloblastic leukemia at diagnosis and in relapse. 141 57

This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2-3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions.
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PMID:The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study. 141 16

Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells.
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PMID:Relationship of [3H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study. 142 99

Aggressive chemotherapy of myelodysplastic syndromes is rarely feasible because these disorders predominantly occur in elderly patients who often have concurrent illnesses. Alternative treatment modalities must therefore be evaluated. This review summarizes the results that have been obtained with low-dose chemotherapy, especially with low-dose cytosine arabinoside (Ara-C). Overall response rates to treatment with low-dose Ara-C are about 40%, with some 20% of patients achieving a complete remission. Transition of MDS to AML does not reduce the probability of response. The therapeutic outcome cannot be reliably predicted by clinical or experimental parameters. Hematological toxicity is substantial, with approximately 10-25% treatment-related deaths. Duration of response is short and rarely exceeds one year. In terms of overall survival, low dose Ara-C does not appear to be superior to supportive care only. Other cytotoxic agents have not been studied in detail, but data available do not suggest an appreciable advantage over Ara-C. Before denying low-dose chemotherapy a helpful role in MDS, randomized studies should concentrate on those patients who can be expected to derive the greatest benefit. Because of their short survival, patients with RAEBt or those transformed to overt leukemia are such candidates.
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PMID:The role of low-dose chemotherapy in myelodysplastic syndromes. 156 Jun 70

Prognosis of second marrow transplantation after leukemia relapse is usually gloomy. We report a patient with AML who was successfully treated by the second marrow transplant following high dose busulfan, etoposide, and Ara-C for the testicular relapse after the first marrow transplantation. A 24-year-old man was diagnosed as having acute myeloid leukemia (AML) in September, 1988. In December of 1989 when he was in early relapse after his 2nd remission, he received the first allogeneic BMT from his HLA identical brother after high dose busulfan and cyclophosphamide conditioning. His posttransplant course was uneventful and graft versus host disease was not observed. Three months after BMT, he noticed swelling on right testicle. Leukemic cell infiltration was confirmed by aspiration cytology. The testicular relapse was followed by marrow relapse. After successful remission induction chemotherapy, he received 17.5 Gy testicular irradiation and second marrow transplantation using high dose busulfan, etoposide, and Ara-C conditioning. Although his posttransplant period was complicated by severe mucositis, high fever and bronchopneumonia, hematologic recovery was obtained by 3 weeks after the second transplant. He is now continuing in complete remission 18 months after the second BMT. This case report suggests that the combination of high dose busulfan, etoposide, and Ara-C could be a choice as a conditioning regimen for resistant AML relapsing after BMT.
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PMID:[Second marrow transplantation following high dose busulfan, etoposide, and Ara-C after testicular relapse in a patient with AML]. 157 38

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.
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PMID:Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872). 157 44

One hundred and nine consecutive patients with de novo acute nonlymphocytic leukemia aged over 56 years were admitted with the intention of administering high-dose cytosine arabinoside (HD Ara-C) intensification. After remission induction, the patients were consolidated with a course of daunorubicin (30 mg/m2/day, days 1-3) and Ara-C (100 mg/m2/day, days 1-7), followed by the intensification (Ara-C, 2 g/m2/12 h, days 1-4). The planned induction course was not started in 13 patients because of cardiac failure or unsatisfactory general status. Remission was achieved in 55% (53/96) of the patients. Twenty-seven patients (28%) had refractory disease, seven died early during induction therapy, five died of hemorrhage and three of infection during the hypoplasia that followed induction treatment. Thirty-nine patients started consolidation and 32 had the planned intensification. In these last patients the 3-year leukemia-free survival (LFS) probability was 29% (SE, 8%). No patient died as a consequence of intensification. The relapse rate of the intensified patients did not differ from the relapse rate of those patients who did not receive the planned intensification (p = 0.12). The only pretreatment variables significantly associated with a better LFS were younger age (p = 0.02) and a low WBC at diagnosis (p = 0.04). For the whole patient group, the 3-year survival probability was 15% (SE, 4%). This study shows that elderly patients can tolerate HD Ara-C. The patients completing consolidation-intensification have a currently acceptable LFS. To what extent HD Ara-C contributed to the length of the remissions remains unclear.
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PMID:High-dose cytosine arabinoside intensification for acute nonlymphocytic leukemia in patients over 56 years of age. 158 6

Since the differentiating effect of high-dose methylprednisolone (HDMP) on myeloid leukemic cells has been shown in one of our patients with acute myeloblastic leukemia (AML-M4), 27 previously untreated children with AML were given HDMP (20-30 mg/kg per day) combined with cytosine arabinoside (Ara-C; 3 mg/kg) for the first 2 weeks of induction therapy. Marked clinical improvement was observed in all patients with the exception of one who died within 24 hours of the treatment. Enlarged liver and spleen (greater than 5 cm) became nonpalpable in 3 (37%) out of 8 and 5 (100%) out of 5 patients, respectively, and bone marrow blasts decreased below 5% in 7 patients (27%) within 2 wk of HDMP and Ara-C treatment. Adriamycin (1 mg/kg) was added 2 wk after initiation of induction therapy. Twenty-two (84.6%) of the 26 patients achieved complete remission, 3 (11.5%) had partial remission and no response was obtained in one. Treatment was well tolerated. The addition of HDMP as a differentiating and/or cytolytic agent to conventional anti-leukemic chemotherapy increased the complete remission rate and prolonged the duration of remission of our AML patients.
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PMID:High remission rate in acute myeloblastic leukemia in children treated with high-dose methylprednisolone. 159 2

The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology.
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PMID:The in vitro growth patterns and drug sensitivities of leukemic blast progenitors among the subtypes of acute myelocytic leukemia. 162 9


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