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)

Acute myelogenous leukemia (AML) of the inbred Wistar/Furth (W/Fu) rat is pathophysiologically similar to human AML. Subcutaneous transplantation of 1.0 X 10(6) cells of a clonal tissue culture line of W/Fu AML into 6- to 8-week-old rats produced local myeloblastomas in 8--10 days which progressed to infiltration of regional nodes, replacement of greater than 90% of the bone marrow, ascites, and fatal peripheral blood leukemia with concomitant hyperlysozymemia. Single doses of adriamycin, daunomycin, actinomycin, cytosine arabinoside, or Cytoxan in rats with 1.0 cm myeloblastomas produced complete tumor regression while bu-sulfan, vinblastine, vincristine, dexamethasone, and Methotrexate was relatively ineffective. Responses were associated with delay in progression to peripheral blood leukemia and prolonged survival. Similar results were obtained following treatment of rats with already disseminated leukemia. The demonstration of response to drugs known active against human AML indicates that the W/Fu AML should be a valuable model for rapid evaluation of new chemotherapeutic agents for clinical use.
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PMID:Chemotherapeutic remissions in Wistar Furth rat acute myelogenous leukemia: a model for human AML. 6 30

The treatment of central nervous system (CNS) involvement in human acute myelogenous leukemia (AML) presents a serious therapeutic dilemma. In an attempt to study the pathophysiology of this diseases in an animal model, the incidence and sites of detection of CNS leukemia were evaluated in inbred rats receiving chemotherapy for the transplantable WF AML. Eight of 100 rats with untreated WF AML demonstrated CNS leukemia at death with concomitant widespread visceral infiltrates, ascites, bone marrow involvement, and peripheral blood leukemia. Similarly, 6 of 120 rats (5%) failing to attain a complete remission following adriamycin. Cytoxan, or cytosine arabinoside chemotherapy demonstrated CNS leukemia in addition to systemic disease at death. In contrast, 70 of 75 rats (93.3%) achieving a complete remission subsequently relapsed in the CNS, either in combination with widespread systemic disease in 48 (64.0%) or with minimal evidence of systemic relapse in 22 (29.3%). There was a greater frequency of detectable cerebral compared to spinal cord infiltrates in relapsing rats. The WF AML appears to be a valuable model for study of the mechanism and ultimately the prevention of CNS relapse following chemotherapy in human AML.
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PMID:Central nervous system (CNS) relapse following chemotherapy of WF rat acute myelogenous leukemia: a model for human CNS leukemia. 26 15

Remission induction was assessed by clinical and cell-culture criteria for 65 patients with acute myelogenous leukemia (AML), 11 patients with chronic myelogenous leukemia (CML) in blast crisis and 19 patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide, cytosine arabinoside and vincristine (CAV) therapy resulted in complete remission in 23 of 50 previously untreated patients with AML and in 3 of the 11 patients with CML. Fourteen patients with ALL responded to vincristine-prednisone induction therapy and two to induction therapy with CAV. The median duration of survival of the responding patients was 2.2 years, compared with 4 months for the patients who did not respond to treatment. Granulopoietic colony formation, assessed by assay of colony-forming units dependent on colony-stimulating activity in culture (CFU-C), was abnormal in 37 of 42 bone marrow aspirates from patients with AML before treatement. CFU-C concentration increased when leukocyte-conditioned medium (LCM) was added to the cultures; 13 cultures had normal or elevated CFU-C concentration with LCM. Marrow cells of patients with ALL or CML in blast crisis demonstrated a similar pattern. Serial studies of marrow CFU-C concentration of 31 patients with AML demonstrated a change to a normal pattern with successful remission induction. Results of this study suggest that administration of purified LCM to leukemic patients might increase granulocyte production from potential but unstimulated granulopoietic precursors. This therapy would lessen the probability of death from infection during remission induction.
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PMID:Acute leukemia in adults: assessment of remission induction with combination chemotherapy by clinical and cell-culture criteria. 105 7

Results of the treatment of 102 acute leukemia patients are presented. The diagnosis in 61 patients was acute myeloid leukemia (AML) and in 41 patients acute lymphoid leukemia (ALL). In the treatment of AML were used Daunorubicyne (DNR), Cytosine arabinoside (ARA-C) or combination of both drugs, some elder patients being treated with 6-mercapropurine. Number of patients were made aplastic and died during the initial phase of therapy. Nine of 24 patients treated with DNR, ARA-C or combined developed complete remission, 6 patients lived for one year and 4 patients two years. ALL patients were treated with Prednisone-Vincristine, Prednisone-Vincristine-DNR and some of them with Prednisone-Vincristine-DNR-Cyclophosphamide-L-Asparaginase combinations of drugs. Complete remission was obtained in 22 out of 32 patients (69%) and 6 patients lived for 2 years.
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PMID:[Results in the treatment of acute leukemias at the Internal Clinic B in the period 1970-1975]. 106 23

Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).
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PMID:Murine and human leukemias. 110 47

A 32-year-old woman was admitted to our hospital with pyrexia and general lymphadenopathy in July 1984. She was diagnosed as having malignant lymphoma (follicular, small cleaved cell), stage IV based on the histological findings of lymph nodes in the neck and bone marrow specimen. She was treated with melphalan orally for 3 years, followed by MACOP-B. She attained partial remission with MACOP-B. Thereafter, she received melphalan or Endoxan orally as maintenance therapy. She developed fever and swelling in the gingivae in October 1989. Peripheral blood showed WBC 80,200/microliters with 7.5% myeloblasts and 85.5% monocytes. Bone marrow aspirate revealed hypercellularity with 47.9% myeloblasts, 46.5% monoblasts and monocytes, which were positive for peroxidase and NSE stains. The karyotype of bone marrow cells showed a 46,XX,t(9;11). The lysozyme in serum was elevated. She was diagnosed having AML (M4). DCMP regimen was initiated but failed to achieve CR. Consequently she received MEC regimen and obtained complete remission, lasting for 6 months. Patients with second leukemia have a low probability of achieving complete remission using conventional chemotherapy. The MEC regimen is thought to be one of the most promising treatments for secondary leukemia.
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PMID:[Complete remission with MEC regimen of acute myeloid leukemia (M4) secondary to 5-year treatment of non-Hodgkin lymphoma]. 128 92

10 patients between the ages of 5 and 40 yrs with myeloid leukemia (4 acute, 6 chronic) in early (5 cases) or intermediate stage of the disease were given Cyclophosphamide and Busulfan (6 cases) or Cyclophosphamide, Busulfan and VP-16 (4 cases with CML) and bone marrow transplants from HLA-matched donors (in 9 cases from siblings and in one case from HLA phenotypically matched father). There was one transplant related death and 3 relapses in CML cases. In cases which relapsed GvHD was not observed. Altogether acute GvH and chronic GvHD was seen in 2 and 4 cases, respectively. All grafted cases with AML survive in continuous remission lasting more than 2 years (median 30.5 month).
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PMID:[Allogeneic bone marrow transplantation in myeloid leukemia: chemical conditioning, clinical course and results]. 148 72

Autologous bone marrow transplantation is widely used as late intensification therapy for patients with AML in remission without an HLA identical donor or who are older than 40-45 years. We report our experience in 21 AML patients in 1st or 2nd CR transplanted with a regimen including HD-ARA-C in addition to Cyclophosphamide (CY) and TBI. The median age was 32 years (3-50). Fourteen patients were transplanted in 1st CR and 7 in 2nd CR. In all but one patient BM harvesting and ABMT were done in the same remission status and after at least 3 courses of consolidation therapy. Two patients (9.5%) died from treatment related toxicity on Day +15 and Day +31. The median time to reach 1000 WBC and 50,000 platelets per cmm was 23 (13-55) and 55 (22-790) days respectively. Only 4 (21%) of the 19 evaluable patients (median observation time of 32 months) relapsed, at 3, 8, 18 and 26 months from ABMT. The projected event free survival curve shows survival of 67% at 96 months with a relapse rate of 26%.
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PMID:Use of high-dose cytarabine in autologous bone marrow transplantation in acute myeloid leukemia. 149 59

Complete remission (CR) rates of 80% are achieved with the AML-BFM protocols but one third of patients relapse within the first three years. There are few reports of treatment of relapsed childhood AML, and these deal with the evaluation of new drugs for frontline therapy. We performed a retrospective analysis to investigate how patients previously treated with the AML-BFM-83 protocol were treated after relapse and how many long term remissions were achieved. 48 of 139 patients relapsed after having achieved complete remission with the AML-BFM-83 protocol which consists of continous infusion of ARA-C 100 mg/m2 day 1-2, ARA-C 200 mg/m2 day 3-8, Daunorubicin 60 mg/m2 day 3, 4, and 5, and VP-16 150 mg/m2 day 6, 7, and 8, and an 8 week consolidation therapy consisting of Prednisolone, Thioguanine, Vincristine, ADR, ARA-C, Cyclophosphamide, intrathecal ARA-C and cranial irradiation followed by maintenance therapy. Duration of first remission ranged from 1.5 months to 66.3 months. Excluding 5 children with either isolated or combined extramedullary relapses and another 4 patients for missing data, 39 children were evaluable. 20 children received no therapy or palliative therapy while 16 patients received chemotherapy and another 3 children were transplanted in relapse. Although 9 different intensive chemotherapy regimens were used for reinduction, a high number (12 of 16 = 75%) of second complete remissions was achieved. Several therapeutic options were used to maintain a second remission: regular maintenance therapy (7 patients), allogeneous bone marrow transplantation (BMT) (2 patients), autologous BMT (3 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of recurrence of acute myeloid leukemia in childhood. A retrospective analysis of recurrence in the AML-BFM-83 study]. 151 61

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).
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PMID:Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse. 1139 26


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