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)

The activation of autologous cytotoxic cells by interleukin-2 (IL-2) may be a promising tool for elimination of minimal residual blast populations in patients with acute myelocytic leukemia (AML) to prolong disease-free survival. Here, we report the results of a phase II study using IL-2 for consolidation therapy in patients with second remission of de novo AML. All patients in 1st relapse of AML received a uniform induction therapy consisting of intermediate high-dose AraC (iHDAraC) 2 x 600 mg/m2 d1-4 and VP-16 100 mg/m2 d1-7. Patients achieving 2nd remission were treated with 4 cycles recombinant IL-2 (rIL-2) 9 x 10(6) IU/m2 administered on d1-5 and 8-12/cycle as 1h infusion every six weeks. In 37/66 (56%) evaluable patients, complete remission (CR) was achieved. So far, 21/37 patients (4 after additional autologous bone marrow transplantation (ABMT) received rIL-2 consolidation. Three patients are too early for evaluation, 4 received allogeneic BMT, 6 relapsed before IL-2 was scheduled and 4 refused treatment with rIL-2. The median disease-free survival (DFS) was 11 (4-49+) months. Up to now, in 5/21 (24%) patients the duration of 2nd remission exceeded that of 1st remission 7/21 (33%) are in ongoing 2nd remission (7+ to 49+ months). The side effects of rIL-2 were generally moderate and manageable. Only in two patients, previously treated with ABMT, severe side effects occurred; septicaemia and pneumonia in one patient and desquamative erythrodermia in the second one. In accordance with other studies rebound lymphocytosis with a marked increase of CD56(+)-cells and release of secondary cytokines such as TNF-alpha, IFN-gamma and IL-6 was observed. The schedule is feasible and the data suggest a possible benefit for DFS, which, however has to be confirmed by randomized trials.
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PMID:Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia. 771 35

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21 (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.
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PMID:[Hemostasis in patients with acute leukemia treated with high doses of cytosine-arabinoside: the effect of chemotherapy and infectious complications on hemostasis]. 781 98

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.
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PMID:Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors. 792 68

The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.
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PMID:Interactions between cladribine (2-chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia. 793 68

We describe a case with acute myelogenous leukemia (AML; M2) who developed prolonged marrow hypoplasia with residual leukemic blasts and recurrent infections after induction chemotherapy. He was treated successfully with a sequential treatment of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine arabinoside (LD AraC). To the best of our knowledge this is the first reported case of a successful treatment of a patient with AML, who showed prolonged markedly hypocellular bone marrow with significant residual leukemic cells after induction chemotherapy, with a sequential treatment of GM-CSF and LD AraC.
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PMID:GM-CSF and low-dose araC treatment of AML in prolonged hypoplasia with residual leukemic cells after induction chemotherapy. 800 2

We treated a 16-month-old girl with myelodysplastic syndrome (MDS; refractory anemia with excess of blasts subtype, RAEB by FAB classification) that developed into acute megakaryoblastic leukemia (ANLL-M7). The blast cells were positive for CD41 shown by flow cytometry and for platelet peroxidase by electron microscopy. Cytogenetically, five kinds of abnormal karyotypes were apparent at the initial visit and karyotypic progression (clonal evolution) was also evident. These karyotypes were considered to be derived from the putative original clone, 48,XX, +6, +21. The observed karyotypes were considered 50,XX, +4,add(4)(q31), +6,add(7)(p22),add(10)(q24),add(12)(q11), +20, +21, + mar[karyotype A];48,XX,add(4)(q31), +6,add(10)(q24),add(12)(q11), +21 [karyotype B];48,XX, +6,t(6;13)(p23;q14), +21 [karyotype C];51,XX, +X, t(6;13)(p23;q14), + der(6)t(6;13)(p23;q14), +21, +21, + mar [karyotype D]; and 49,XX, +X, -3,t(6;13)(p23;q14), +der(6)t(6;13)(p23;q14), -12, +21, +21, + mar [karyotype E]. It seems karyotypes B and C were derived from the putative clone; karyotype B developed into karyotype A; and karyotype C developed into karyotype E through karyotype D. After development of ANLL-M7, the cytogenetic study showed a karyotype with further karyotypic progression. The patient was treated with high-dose cytosine arabinoside (HD AraC) followed by allogeneic bone marrow transplantation. Despite intensive care, she died 3 months after the transplantation.
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PMID:Childhood myelodysplastic syndrome with clonal evolution progressing to acute megakaryoblastic leukemia (ANLL-M7). 822 7

193 patients with relapsed or refractory acute myeloid leukemia (AML) were entered into a prospective randomized comparison of high-dose versus intermediate dose cytosine arabinoside (AraC) both combined with mitoxantrone (mitox) according to the previously established sequential HD-AraC/mitox regimen (S-HAM). AraC was administered by 3 hr inf. q 12 hrs on days 1, 2, and 8, 9 at randomly assigned doses of either 3.0 versus 1.0 g/m2 in pts. < 60 years of age or 1.0 versus 0.5 g/m2 in older pts. Mitox was given to all cases at a dose of 10 mg/m2/d on days 3, 4, and 10, 11. Randomization was stratified for primary refractoriness against induction therapy and the length of first remission in relapsed cases (< 6 mths., 6-18 mths., > 18 mths.). From 151 presently evaluable cases 72 pts (48%) achieved a complete remission (CR), 38 cases (25%) were non-responders (NR) and 41 pts. (27%) died within the first 6 weeks after the start of treatment (early death = ED). No significant differences were found in CR rates being 52% and 44% for the 3.0 versus 1.0 g/m2 AraC regimens in pts. < 60 years and 48% and 45% after 1.0 versus 0.5 g/m2 AraC in older pts. No differences between the respective regimens emerged either for the time to CR (median 46 days) nor remission duration (median 4.5 mths). Analysis of treatment failures, however, demonstrated a significantly higher rate of NR after the lower dose regimens in both age groups of 41% and 32% versus 11% and 14% in pts. receiving AraC at higher doses (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison. 848 62

A new flow cytometric method is described to detect DNA strand breaks associated with apoptosis, by labeling the 3'-OH termini in the breaks with biotinylated dUTP in a reaction employing exogenous terminal deoxynucleotidyl transferase. The method has been applied in studies on leukemic HL-60 and MOLT-4 cell lines to reveal whether it is specific to apoptotic cells, and whether it can be used in the clinic to detect DNA breakage in leukemic cells during chemotherapy. There was labeling of mononuclear cells in peripheral blood of all 11 patients studied during chemotherapy for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia (ALL, AML, or CML) in blastic crisis, indicating induced DNA damage; the number of labeled cells increased from 1-8% before treatment up to 80% during the course of treatment. The DNA topoisomerase inhibitors mitoxantrone, VP-16 (etoposide), and m-AMSA (amsacrine) were more effective in inducing DNA breaks than was hydroxyurea or cytosine arabinoside (AraC). Cells with DNA breaks were identified in peripheral blood for up to 5 days following administration of Mitoxantrone and VP-16. In the case of DNA aneuploid leukemias, the DNA breaks were predominant in the aneuploid cell subpopulations, whereas presumably non-neoplastic diploid cells were unlabeled. In one case of ALL there were two distinct subpopulations of aneuploid cells: one responded to the treatment (by DNA breakage) and the other was non-responding. Thus, cells undergoing apoptosis can be detected by this method of labeling DNA strand breaks and the technique is applicable for analysis of response of leukemic cells to chemotherapy. With this method it may be possible to identify tumor cell sensitivity or resistance to particular drugs early in the course of treatment.
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PMID:Induction of DNA strand breaks associated with apoptosis during treatment of leukemias. 848 18

Acute leukemia (AL) is a relatively uncommon, but dreaded, complication occurring with increased frequency in individuals with Down syndrome (DS). This selective update includes aspects of AL in DS in which a change or advancement in our understanding of this disease has occurred. Despite previous reports describing a worse outcome for these individuals, more recent studies have suggested an improved response to current treatment strategies (including high-dose AraC) equaling, or even surpassing, the survival of non-DS individuals with AL. An increased toxicity to methotrexate in DS patients has also been recognized. While the leukemia of DS infants has been described as megakaryoblastic, the spectrum of in vitro differentiation is much broader including (in addition to megakaryocytic colonies) various myeloid, macrophage, and even erythroid colonies. Although the cause(s) of DS-AL remains unknown, potential candidate genes include those encoded on chromosome 21 that play a role in other defined leukemias in non-DS individuals. The AML1/PEBP2alpha gene maps to the DS critical region and is characteristically associated with two leukemia-associated chromosomal translocations: 1) the 8;21 translocation involving an AML1/ETO fusion transcript commonly seen in acute myelogenous leukemia (AML) and; 2) a 3;21 translocation identified in certain chemotherapy-related myelodysplasias/leukemias and occasionally in the blast crisis of chronic myelogenous leukemia cells. Similarly, the ETS-related gene, ERG, involved in the AML 16;21 maps to the q22 region of chromosome 21. Lastly, a familial platelet disorder with a propensity to develop myeloid leukemia has been linked to 21q22.1-22.2 and conceivably might involve AML1, ERG or yet another gene.
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PMID:Down syndrome and leukemia, an update. 854 49

We report a case of AML with diabetes insipidus (DI). A 68-year-old female was admitted to our hospital because of fever and leukocytosis. The WBC was 197,000/microliter with 98% blasts positive for myeloperoxidase, CD33, CD34 and HLA-DR. While, on admission, urine volume was more than 6 liters daily. Blood vasopressin level was 0.3 microgram/ml. The patient was diagnosed as having AML with DI. By chemotherapy consisting of BHAC, DNR, 6-MP and PSL and intrathecal administration of AraC, MTX and PSL, and nasal drip of DDAVP, complete remission was attained and the urine volume was reduced to normal. Finally DDAVP became unnecessary. Although the exact cause of DI cannot be ascertained, rapid increase of leukemic blasts and leukostasis in small vessels might be associated with hypothalamus-pituitary system damage. Reportedly, DI is a rare complication of leukemia and administration of DDAVP could be halted in only two patients with leukemia and DI.
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PMID:[Acute myelogenous leukemia with diabetes insipidus without desmopression administration by anti-leukemic chemotherapy]. 858 72


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