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)

One hundred ninety six previously untreated patients of adult acute nonlymphocytic leukemia (ANLL) were treated with B-DOMP therapy. 102 patients were treated in the conventional rooms and 94 patients were in the laminar airflow rooms. The complete remission (CR) rates were 78.4%, and 84.0% respectively. The CR rate of the groups whose age was 60 years or older was higher for the patients treated in the laminar airflow room than those is conventional rooms (75.8% versus 60.0%), and the fatality from fungal infection was substantially lower for the laminar air-flow room patients. Non cross resistant chemotherapy based on alternate administration of Daunorubicin (DNR) and Aclarubicin (ACR) was given to 54 patients with ANLL in remission. The median duration of remission was 48.0 months, with 38.4%, patients in remission at 8 years. A plateau phase indicating freedom from the risk of leukemic recurrence is not clearly apparent yet. The most serious toxicity was drug induced cardiotoxicity from increased total dose by long term maintenance therapy. Newly planned post remission chemotherapy that incorporated Etoposide and Mitoxantrone with ACR and DNR was given to 35 patients with ANLL in remission. Seventy nine percent (79%) of patients were remaining in remission at 2 years. Because many patients experienced significant side effects after each course of therapy, intensive post remission chemotherapy should be used in a setting where the physician is always attending and ready to serve the patients.
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PMID:[Chemotherapy of adult ANLL]. 260 Oct 24

21 patients with hematological neoplasias (8 ALL, 4 AML, 4 NHL, 5 HD) were treated with high dose therapy and autologous bone marrow rescue (ABMT). At the time of ABMT 12 patients were in CR, 6 in PR and 3 in relapse. 66% of the patients were at high risk at the time of diagnosis. Before ABMT patients received an ablative regimen such as cyclophosphamide or ARA-C, VP-16, DNR and 12 Gy TBI in 6 fractions. In 9 patients the bone marrow was treated in vitro with monoclonal antibodies and complement. The hospital stay was a median 33 (24-57) days and isolation 19 (9-49) days. Complications were septicemia (7), herpes stomatitis (7), infections (6), fungal sepsis (1) and hemorrhagic cystitis (2). Late complications (up to 6 months after ABMT) were pneumococcal sepsis (1), cerebral toxoplasmosis (1) and herpes zoster (3). 10 of 19 evaluable patients are alive and relapse-free 1-33 months (median 10) after ABTM, and 3 of 10 more than 2 years later: 4 of 5 were transplanted in 1. CR, 4 of 6 in greater than or equal to 2. CR and 2 of 8 in PR. 4 patients are living in therapy sensitive relapse 2, 11, 11 and 39 months after ABMT in 2. CR or PR. 5 patients died 1-13 (median 3.5) months on relapse, 2 of 21 from septicemia. The morbidity of ABMT is comparable with conventional high dose chemotherapy. Relapse-free survival was significantly influenced by the remission status at ABMT. Long-term survivors can be expected even in patients with high risk hematological malignancies. However, only wider trials will serve to establish the efficacy of ABMT.
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PMID:[Autologous bone marrow transfusion in the treatment of adults with hematologic neoplasms. Experiences from Bern]. 266 30

Etoposide, an epipodophyllotoxin structurally related to vincristine, is active in solid tumors. Trials of etoposide in hematologic malignancies, particularly leukemia and lymphoma, were initiated in 1973. Subsequent studies indicate that etoposide, either as a single agent or in combination with other drugs, is active in acute myelogenous leukemia, non-Hodgkin and Hodgkin lymphoma. Etoposide may be effective in acute lymphoblastic leukemia, but it is inactive in chronic myelogenous leukemia. The major toxicity of etoposide is myelosuppression. Non-hematologic toxicity is relatively mild at doses up to 2000 mg/m2. This feature favors its use in high dose regimens such as those employed before bone marrow transplantation. Preliminary studies of etoposide in autologous bone marrow transplantation in lymphoma and Hodgkin disease are promising. Studies of high dose etoposide in combination with other chemotherapeutic agents or in the context of bone marrow transplantation are in progress.
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PMID:Etoposide in leukemia, lymphoma and bone marrow transplantation. 267 26

Nineteen children (median age, 13 years; range 4 to 18 years) with acute lymphoblastic leukemia/lymphoma (ALL) (10 patients) or acute nonlymphoblastic leukemia (ANNL) (9 patients) received allogeneic bone marrow transplants (BMT). Marrow was taken from HLA-identical sibling donors (16 patients) (pts), HLA-identical unrelated donor (1 pt), or one-antigen-missmatched sibling donor (1 pt). Preparatory regimen consisted of fractionated total body irradiation and high-dose VP-16 (50-70 mg/kg body weight). At the time of BMT nine of the pts were not in complete remission (CR): seven pts were refractory to aggressive multiagent chemotherapy and two pts were in first relapse. Six pts were in second CR, one pt in third CR; three pts grafted in first CR carried additional risk factors; e.g. induction failure. Ten out of the nineteen pts are alive and free of disease between one and 53 months (median, 28 months) after BMT. The actuarial disease-free survival rate is 37% for pts with ANLL and 54% for pts with ALL. Six pts have died from BMT-related complications. Only three pts (1 pt with ALL, 2 pts with ANLL) have relapsed between day +106 and day +134 after BMT and subsequently died. The four-year actuarial relapse rates of 29% for ANLL and 14% for ALL, respectively, demonstrate that the combination of fractionated total body irradiation and high-dose VP-16 is an effective antileucemic regimen for children with advanced leukemias.
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PMID:Fractionated total body irradiation plus high-dose VP-16 prior to allogeneic bone marrow transplantation in children with poor risk acute leukaemias. 269 28

Twenty patients with refractory AML were treated with mAMSA and VP 16-213 in combination to assess the toxicity and anti-leukemic activity of the two-drug regimen. Refractoriness was defined according to the response to induction therapy consisting of 6-thioguanine, cytosine arabinoside and daunorubicin (TAD9) and the duration of the preceding remission. Patients were eligible for AMSA/VP 16-213 if they were primary non-responders against two TAD9 induction courses, had early relapses within the first six months, were nonresponders to one additional TAD9 course at later relapses or were at second or subsequent relapses. Therapy consisted of a five-day course of mAMSA 210 mg/m2/d on days 2, 3 and 4. VP 16-213 was applied on days 1 and 5 by a 1-h infusion of 100 mg/m2 followed by a 23 h infusion, the dosage of which was escalated in three steps from 110 mg/m2 over 200 mg/m2 to 230 mg/m2 in subsequent patients. Even at the highest dose of VP 16-213, toxicity was mild to moderate except for mucositis of grade III after two cycles and severe intrahepatic cholestasis in one case. Four of the 20 patients died within the first three weeks after the onset of treatment and were not evaluable for the assessment of antileukemic efficacy. From the remaining 16 patients five achieved partial remissions while no complete remission was obtained. Four of the five PR occurred in the eight patients with primary TAD9 resistance. These data indicate that AMSA/VP 16-213 reveals a moderate toxicity only, and that the combination may not be completely cross-resistant with TAD9. The overall anti-leukemic activity is limited however, and seems inferior compared to other presently available salvage regimens in refractory AML.
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PMID:Treatment of refractory acute myeloid leukemia with mAMSA and VP 16-213 in combination: results of a clinical phase I/II study. 273 7

The presumptive intracellular target of the anti-leukemia agents 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 4-(4,6-O-ethylidene-beta-D-glucopyranoside) (VP-16) is the enzyme topoisomerase II. We found that 350 mM NaCl extracts of nuclei from HL-60 and HL-60/AMSA, an m-AMSA resistant HL-60 subline, contained equivalent topoisomerase II activity. However, the ability of m-AMSA to stimulate cleavage of exogenous DNA and to stimulate crosslinking of exogenous DNA with protein, processes which are topoisomerase II-mediated, was greatly reduced in the HL-60/AMSA extracts compared to the HL-60 extracts. HL-60 and HL-60/AMSA were almost equally sensitive to the cytotoxic effects of VP-16 and differences in VP-16-stimulated, topoisomerase II-mediated exogenous DNA cleavage and protein crosslinking between HL-60 and HL-60/AMSA extracts were much less than the differences in m-AMSA-stimulated exogenous DNA cleavage and protein crosslinking. Thus, the interaction between topoisomerase II activity, exogenous DNA, and m-AMSA or VP-16 indicated the susceptibility HL-60 and HL-60/ AMSA to the cytotoxic effects of the drugs. A similar correlation may exist in explanted leukemia cells from patients with acute myelogenous leukemia.
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PMID:The interaction between nuclear topoisomerase II activity from human leukemia cells, exogenous DNA, and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) or 4-(4,6-O-ethylidene-beta-D-glucopyranoside) (VP-16) indicates the sensitivity of the cells to the drugs. 303 64

All clinical studies in the English literature from 1976 to mid-1987 that address drug management of refractory or relapsed ANLL are reviewed and summarized. We conclude that, although many regimens may induce a CR, none is clearly superior. New drugs and or drug combinations must be sought if treatment outcomes are to be substantially improved. At present it appears that combination chemotherapy with VP-16 has not been extensively studied and may be active in non-cross-resistant regimens.
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PMID:Impact of reinduction regimens on the clinical course of adult acute nonlymphocytic leukemia. 305 48

Thirty-five patients with acute myelogenous leukemia were treated with aclacinomycin A (60 mg/m2/day for 5 days) and VP-16-213 (100 mg/m2/day for 5 days). All were previously treated and had relapsed or were refractory to primary treatment. Most patients (28) had received prior DAT (daunorubicin, cytosine arabinoside, and 6-thioguanine) induction therapy followed by one or more courses of high-dose cytosine arabinoside (HD-Ara C) as consolidation therapy or as treatment for relapse. One patient was in her fourth relapse, one had relapsed acute megakaryoblastic leukemia (following remission with DAT and HD-Ara-C), one had a treatment-induced leukemia, and four patients were treated for primary treatment failures following two induction courses with DAT or a similar regimen. Fourteen patients had infections at start of therapy. Ten patients died within 14 days of treatment, all from sepsis or bleeding, before their marrow could be evaluated for leukemic response. Fourteen patients (40%) responded; 12 (34%) entered complete remission and two (6%) a partial remission (PR). Two of the four patients who were treated for primary treatment failures went into CR. The median CR duration was 99 days (range 30 to 455 days). Side effects from this treatment were similar to the conventional DAT regimen, although the gastrointestinal toxicity and mucositis appeared to be more severe. In addition, two of the patients had severe but reversible ventricular arrhythmias. The overall response (40%) and CR rate (34%) in this group of previously treated AML patients is encouraging, and further studies are needed to evaluate these preliminary findings.
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PMID:Aclacinomycin A and etoposide (VP-16-213): an effective regimen in previously treated patients with refractory acute myelogenous leukemia. 316 95

In a prospective multicenter study the efficacy and toxicity of an induction therapy with daunorubicin, cytosine-arabinoside and VP 16-213, followed by an intensified consolidation with high-dose cytosine-arabinoside and daunorubicin, is evaluated in adult patients with acute myelogenous leukemia. The upper age limit for inclusion in the study was 50 years. Within the first two years of this study 91 patients were enrolled. In 84 patients who have finished the remission induction therapy the rate of complete remissions is 67%. The median survival time of all patients is 22 months and the probability of survival is 46% after 24 months. So far 34 patients in complete remission have been given one or two courses of the intensified consolidation therapy with high-dose cytosine-arabinoside and daunorubicin. The probability of relapse-free survival in these patients is 46% after 22 months and the median remission duration is 20 months.
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PMID:[Induction and intensive combined therapy of acute myeloid leukemia in adults]. 328 26

We tested the value of early intensification of chemotherapy in 68 consecutive children with acute nonlymphocytic leukemia (ANLL) who were admitted to St. Jude Children's Research Hospital from November 1983 through March 1987. Fifty-eight patients (85%) entered complete remission after treatment with etoposide (VP-16)/cytarabine (ara-C) (A), followed by daunorubicin (Dauno)/ara-C/thioguanine (6-TG) (B) and then VP-16/azacytidine (5-AZ) (C). Thirty percent of the complete responders, mainly those with an M4 or M5 leukemia subtype, attained M1 marrow status after component A, 60% after A + B, and 10% after A + B + C. Induction failures resulted primarily from absolute or relative drug resistance; there was only one death during this phase of therapy. Postremission treatment consisted of three pairs of drugs (vincristine [VCR]/amsacrine [m-AMSA], or doxorubicin [Doxo]/6-TG/ara-C, and VP-16/cyclophosphamide [CTX]) administered sequentially in 6-week cycles for 22 months. Despite the high rate of remission induction, only 33% +/- 7% SE of the patients are expected to be failure-free survivors at 2 years. Remission durations were not significantly affected by the majority of factors examined in this study, with the exception of marrow cellularity after VP-16/ara-C induction therapy. Patients with less than or equal to 5% leukemic cells survived relapse-free for a median of 36.1 months, compared with 11.3 months for the group with a larger infiltrate (P = .01). Although postremission therapy did not improve the percentage of long-term failure-free survivors, the induction regimen we used appears highly effective, and its components should be considered for inclusion in other treatment programs.
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PMID:Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five-drug regimen including etoposide. 329 13


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