Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.
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PMID:Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine. 689 90

Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
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PMID:Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia. 693 51

AMSA was evaluated in the treatment of 109 adults with previously treated acute leukemia. Of the 102 evaluable patients, 82 had AML, 17 ALL, and 3 CML in blastic phase. A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days. Complete remissions were observed in 23 (28%) patients with AML and in 1 patient with ALL. Patients who achieved complete remission were maintained on AMSA using a dose of 30-40 mg/sq m/day for 5 days repeated at 4-wk intervals. The median duration of complete remission was 12 wk (3-59 wk), and the responders survived significantly longer than the failures (27 wk versus 8 wk, p = 0.002). The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections. Our results indicate that AMSA is a useful new antileukemic agent for the treatment of relapsed acute leukemia and appears to have activity comparable to that of the currently available drugs, such as cytarabine and the anthracycline antibiotics.
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PMID:Evaluation of AMSA in previously treated patients with acute leukemia: results of therapy in 109 adults. 695 87

Ten patients with AML refractory to anthracyclines and cytosine arabinoside were treated with vincristine 1.4 mg/m2 and methotrexate (MTX) 2.5 gm/m2 by intravenous (IV) bolus on day 1 [citrovorum factor (CF) rescue began 24 h later], BCNU 80 mg/m2, and cyclophosphamide 900 mg/m2 IV 36 h after MTX and MGBG 300 mg/m2 IV over 1-2 h on days 3, 4, and 5. Bone marrow aplasia was achieved in all patients by day 12. Five patients (50%) achieved complete remission (CR). Two patients died of sepsis during induction. The median duration of remission was 24 weeks (range 8-38). Maintenance therapy was employed in three patients (high-dose MTX-CF in 2 and MGBG plus BCNU in 1), but did not appear to significantly increase the duration of remission. Nausea and vomiting occurred in eight patients. Five patients developed moderate stomatitis and one developed a moderately severe cutaneous reaction. This pilot experience demonstrates that patients with refractory AML can achieve CR after aggressive treatment with so-called second-line drugs. and may indicate that collateral sensitivity to MTX exists in cells which have become resistant to anthracyclines, a situation we previously described in an experimental cell line.
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PMID:Treatment of patients with refractory myelogenous leukemia with BCOMM[1,3-bis-chloro(2-chloroethyl)-1-nitrosourea (BCNU), oncovin (vincristine), cyclophosphamide, high-dose methotrexate and methyl-glyoxal bis-guanylhydrazone (MGBG)]. 695 16

Cyclic administration of methotrexate (MTX) and L-Asparaginase (L-Asp) was utilized either as induction and maintenance chemotherapy or as maintenance chemotherapy alone following induction with other medications in treating 36 children with multiple relapses of acute leukemia. A complete remission rate (CR) of 67% was obtained in children with null-cell acute lymphocytic leukemia (ALL). The average length of remission was greater than four months. One of three patients with T-cell ALL and one of two patients with B-cell ALL achieved CR. In six cases of acute nonlymphocytic leukemia (ANLL), two patients achieved CR. One of two patients with terminal deoxynucleotidyl transferase (TdT) negative myeloblastic transformation of Ph'-positive chronic myelogenous leukemia (CML) obtained a CR lasting 20 weeks. Toxicity secondary to the chemotherapy included bone marrow suppression, hepatic injury, nausea, diarrhea, stomatitis, and allergic reactions to L-Asp. One case of subacute necrotizing leukoencephalopathy was seen.
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PMID:Methotrexate/L-asparaginase combination chemotherapy for patients with acute leukemia in relapse: a study of 36 children. 696 21

The treatment of refractory acute nonlymphocytic leukemia remains a major clinical problem in leukemia therapy. VP 16-213 is an investigational agent that may have specificity for monocytic blasts, and the combination of VP 16-213 and cyclophosphamide is synergistic in experimental leukemia. Seven patients with highly refractory acute nonlymphocytic leukemia, which demonstrated monocytic features, were treated with a combination of VP 16-213 and cyclophosphamide after they had failed to respond to multiple courses of intensive induction regimens. Three complete remissions and one partial remission were achieved. The times to complete remission were 21, 23, and 34 days. The durations of complete remission were 5, 9, and 12+ months. Myelosuppression was the most common side effect; one patient experienced nausea and stomatitis. There were no documented infections or hemorrhage, and no one died as a result of therapy. This combination is both well tolerated and effective in the treatment of refractory leukemia with monocytic features.
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PMID:VP 16-213 and cyclophosphamide in the treatment of refractory acute nonlymphocytic leukemia with monocytic features. 701 68

Forty-five patients with various forms of acute leukemia refractory to usual methods of treatment were treated with AMSA at doses of 100-200 mg/m2 iv daily for 5-7 days, for total doses of 500-1000 mg/m2/course. Among 41 evaluable patients, six (15%) achieved complete remissions, including two of 19 patients with typical acute nonlymphocytic leukemia, none of four with atypical acute nonlymphocytic leukemia, two of nine with chronic granulocytic leukemia in blast crisis, two of eight with acute lymphoblastic leukemia, and none of one with acute undifferentiated leukemia. Durations of complete remissions were 6, 7, 8, 12, 13, and 14 weeks. Four of the patients who died with infection during marrow hypoplasia 2-5 weeks after receiving AMSA had no evidence of leukemia on premortem bone marrow aspirates or postmortem examination. The primary toxic effects of AMSA were severe myelosuppression, stomatitis, and alopecia. One incident of life-threatening liver failure occurred. AMSA appears to be a promising agent for use in heavily pretreated patients with acute leukemia and chronic granulocytic leukemia in blast crisis.
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PMID:AMSA--a promising new agent in refractory acute leukemia. 704 28

Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in second relapse or refractory were treated with menogaril, 100 mg/m2/day as a 90-min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47), and there was one partial response. Seven of eight responders were in first relapse with a 26% response rate among first relapse patients (7/27). The median duration of survival was 3 months for all first relapse patients and 4.3 months for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100% of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3 arrhythmias and one heart block). All had previously received anthracyclines. Remission duration was 1.6-48+ months; two patients underwent bone marrow transplantation and continue in CR at 36+ and 48+ months. The nontransplanted patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity of menogaril in this study were comparable to that of other clinically useful anthracyclines in AML. Further investigation of this agent in AML is warranted.
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PMID:A phase II study of menogaril (7R-O-methylnogarol) in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group. 756 2

To confirm the reported correlation of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) serum concentrations with nonhematologic toxicity after cytotoxic chemotherapy and to examine their possible effects on hematopoiesis, we evaluated serum TNF-alpha and IL-6 concentrations every 3 days during 21 chemotherapy cycles in 11 patients with acute myelogenous leukemia (AML) and one patient with chronic myelogenous leukemia in blast crisis (CML-BC). All patients developed grade IV hematologic toxicity. In 13 patient cycles, grade III-IV nonhematologic toxicity developed: hepatic (nine), pulmonary (six), and stomatitis (five). In these patient cycles, IL-6 concentrations increased from 10.1 pg/mL (4.6-15.6, 95% CI) before nonhematologic toxicity to 64.8 (5.3-124.2, 95% CI) at the onset of toxicity (p = 0.02). TNF-alpha concentrations were not detectable before nonhematologic toxicity but increased to 20.4 pg/mL (not detectable [ND]-45.5, 95% CI) at the onset of grade III-IV toxicity. In six patient cycles, grade II nonhematologic toxicity developed: hepatic (five), pulmonary (one), and stomatitis (two). In these six, IL-6 concentrations increased from 12.1 pg/mL (6.8-17.4, 95% CI) before toxicity to 21.4 (11-31.8, 95% CI) at the onset of toxicity (p = 0.03). TNF-alpha concentrations were detectable in one patient cycle before toxicity and detectable in only two patient cycles at the onset of toxicity. The peak IL-6 and TNF-alpha concentrations did not correlate with the onset of nonhematologic toxicity in 87% of patient cycles. In patient cycles with a cumulative IL-6 area-under-the-serum concentration vs. time curve (AUC) > 1000 pg/mL.d, platelet recovery (> 30 x 10(9)/L and platelet transfusion-independent) occurred earlier at 21.9 days (18.7-25.1, 95% CI) compared to the 30.6 days (23.6-37.5, 95% CI, p = 0.02) in patient cycles with an IL-6 AUC < 1000 pg/mL.d. Patient cycles with a cumulative TNF-alpha AUC > 150 pg/mL.d required a mean of 17.5 units of red blood cells (RBCs) (9.3-25.7, 95% CI) compared to patient cycles with an AUC < 150 pg/mL.d, which required only 8.9 units of RBCs (6.2-11.7, 95% CI, p = 0.03). The peak concentration and AUC for IL-6 and TNF-alpha were not significantly different between those receiving growth factors (G-CSF, six; GM-CSF, one) and those not receiving growth factors (14). Endogenous IL-6 and TNF-alpha serum concentrations increase in patients who experience nonhematologic toxicity and correlate with hematologic recovery after chemotherapy.
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PMID:The influence of serum tumor necrosis factor-alpha and interleukin-6 concentrations on nonhematologic toxicity and hematologic recovery in patients with acute myelogenous leukemia. 758 79

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.
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PMID:Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia. 768 79


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