Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to examine the effect of hematopoietic stem cell transplantation (HSCT) on cardiac systolic function, we measured left ventricular ejection fraction (LVEF) by radioventriculography (RVG) before and after the transplantation procedure. One hundred and forty-eight patients were examined, 96 undergoing allogeneic grafting and 52 autologous. Fifty patients had CML, 48 AML, 21 ALL, 18 multiple myeloma and 11 breast cancer. The second RVG examination was performed 22 to 227 days (median 60 days) after HSCT. The mean LVEF value in the whole patient group was 60.2% (range 39-81%) before and 61.1% (35-86%) after transplantation. Patients with CML had significantly higher LVEF before transplantation than patients with acute leukemia (P = 0.007) and multiple myeloma (P = 0.005). No significant changes in mean LVEF between the pre- and post-transplant measurements were seen in any of the diagnostic subgroups or in allogeneic or autologous recipients. None of the 148 patients in the study has shown any signs of clinical heart failure at 2, 5 to 10 years follow-up. Patients who had received anthracyclines in the previous treatment had significantly lower LVEF before transplantation but showed no increased risk of decline in cardiac function. In conclusion, the HSCT procedure does not seem to affect myocardial function 1-7 months after transplantation.
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PMID:Cardiac systolic function before and after hematopoietic stem cell transplantation. 1091 29

The purpose of this study was to assess the feasibility and efficacy of a treatment regimen for pediatric acute myelogenous leukemia (AML) that uses four rotating drug pairs and adjusts dosages of etoposide and cytarabine to target specific plasma concentrations. Thirty-one girls and 27 boys (median age, 9.7 years) with de novo AML were treated on the protocol. Six cycles of chemotherapy were planned. Cycles 1 to 4 comprised the drug combinations cytarabine plus etoposide, cytarabine plus daunomycin, etoposide plus amsacrine, and etoposide plus azacitidine, respectively. For cycles 5 and 6, the first two combinations were repeated. Dosages were adjusted to achieve plasma concentrations of 1.0 microM +/- 0.1 microM cytarabine and 30 microM +/- 0.3 microM etoposide. Forty-four patients (76%) entered complete remission. Of those, 24 have had relapses; 23 remain alive in first or subsequent remission. The 5-year event-free survival (EFS) estimate was 31.0% +/- 5.9%; the 5-year survival estimate was 41.4% +/- 6.3%. Six patients (10%) died of the toxic effects of therapy. Severe neutropenia occurred in all cycles. Long-term complications of therapy included hepatitis C, cardiac insufficiency, and hearing loss. Adjustment of cytarabine and etoposide dosage was feasible for achieving targeted plasma drug concentrations; however, the potential clinical efficacy of this approach was offset by substantial acute and long-term toxicity.
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PMID:Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects. 1102 48

A 17-year-old male with AML FAB M4 relapsed 4 months after myeloablative conditioning and peripheral blood stem cell transplantation (PBSCT) from an HLA-identical unrelated donor. A second PBSC harvest was infused 2 days after completion of cytoreductive therapy with mitoxantrone 7 mg/m(2)/day i.v. for 3 days (total dose 21 mg/m(2)), fludarabine 30 mg/m(2)/day i.v. for 6 days (total dose 180 mg/m(2)) and Ara-C 125 mg/m(2)/day i.v. for 5 days (total dose 625 mg/m(2)). Neutrophil recovery occurred on day +10 and was associated with GVHD grade III of the skin which was treated with cyclosporin A (CsA) and prednisone. Because of fever of unknown origin and progressive fatigue combined with hypotension on day +15 after second PBSCT, echocardiography was performed which revealed a dramatic decrease in systolic function compared to the status pre-transplant. On the same day acute heart failure with consecutive ventricular fibrillation occurred. Although resuscitation was performed immediately the patient died. The autopsy revealed massive infiltration by donor CD8-positive lymphocytes with concomitant extensive damage of the heart tissue. Acute myocarditis of viral origin was excluded by in situ hybridization and nested PCR techniques. In this patient, myocardial involvement by acute GVHD seems to have triggered a fatal arrhythmia and heart failure.
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PMID:Acute heart failure after allogeneic blood stem cell transplantation due to massive myocardial infiltration by cytotoxic T cells of donor origin. 1124 47

Between 1992 and 1999, 5 patients with chronic idiopathic myelofibrosis (MF) underwent splenectomy at our hospital. The median age at the time of splenectomy was 63 years (range, 58-69 years), while the median interval from diagnosis of MF to splenectomy was 38.2 months (range, 3.7-87.2 months). Reasons for splenectomy included symptomatic splenomegaly in 5 patients, transfusion-dependent anemia in 5, and refractory thrombocytopenia in 3. Although most of the patients with transfusion-dependent anemia and thrombocytopenia showed some improvement at 1 month after splenectomy, the response was durable in only 2 patients at 6 months. Post-surgical thrombocytosis of 1020 x 10(9)/l was observed in one patient. Blast cell counts in peripheral blood increased after splenectomy in 4 patients. Leukemic transformation occurred in one patient 5 months after splenectomy. Four patients eventually died (2 of infection, 1 of acute myelocytic leukemia, and one of heart failure). Overall median survival was 54.7 months (range, 10.9-110.0 months) and 10.2 months (range, 6.0-33.6 + months) from diagnosis and time of splenectomy, respectively. We confirmed the palliative role of splenectomy in advanced-stage MF, but sufficient consideration should be given to late complications including blastic transformation.
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PMID:[Splenectomy in 5 patients with idiopathic myelofibrosis]. 1157 2

We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA. Patients belonged to the following cytogenetic groups: 15 complex abnormal karyotypes, 12 normal karyotypes, four cases with 5q- as sole anomaly and three single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients). Four patients discontinued the study after less than 5 weeks, because of fatigue (three) or skin rash (one). One patient died of heart failure after 4 weeks. In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria. Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease. Hematological improvement (HI) was observed in 19 patients. Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or =100,000/microl. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence. Six patients (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI-E+HI-N). Hematological improvement occurred after a median of 2 months of thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).
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PMID:Thalidomide for the treatment of patients with myelodysplastic syndromes. 1184 Feb 56

Daunorubicin (DNR) is one of the most important cytotoxic agents in the treatment of acute myeloid leukemia (AML). Its use is usually limited by drug-induced cardiotoxicity depending on the cumulative dose administered. Liposomal encapsulation of DNR (DaunoXome, DNX) seems to reduce the risk of this severe side effect. To investigate the toxicity of DNX in heavily pretreated patients, we conducted a phase I trial, including patients (pts) older than 60 years with relapsed or refractory AML. DNX was used at doses of 40, 60, 75 and 90 mg/m(2), biweekly. Fourteen patients with a median age of 69 years (range, 63-77) were enrolled. A total of 49 courses of DNX were administered [3 pts at 40 mg/m(2) (for a total of 13 courses), 5 at 60 mg/m(2) (20 courses), 4 at 75 mg/m(2) (12 courses), and 2 at 90 mg/m(2) (4 courses)]. The mean cumulative dose of DNX administered was 340 mg (range, 120-1200). A 20% decline in the left ventricular ejection fraction (LVEF) without clinical signs and symptoms of heart failure was noted in 2 patients after a cumulative DNX dose of 480 mg, both with pre-existing heart disease. Even at the highest cumulative doses of DNX, no further decline in LVEF was noted. Nausea, vomiting, alopecia and mucositis were absent. All patients had significant myelosuppression requiring transfusion support. During treatment, 3 patients showed a 25% reduction of leukemic blasts in the bone marrow, 3 patients had to be excluded due to AML progression after the 2nd DNX course, and 7 patients died during the first 6 weeks of treatment. We conclude from these data that DNX offers a less toxic alternative to DNR and other anthracyclines. Using DNX dosages of 40 to 90 mg/m(2) biweekly seems to have little anti-leukemic activity in a patient population heavily pretreated with anthracyclines.
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PMID:Phase I study of liposomal daunorubicin in relapsed and refractory acute myeloid leukemia. 1279 45

Acute myeloblastic leukemia, subtype M1, was diagnosed in a 39-year-old G2P1 Japanese woman at 21 weeks' gestation. Remission-induction polychemotherapy, including daunorubicin, performed for one cycle, did not lead to remission. Second-line chemotherapy, including idarubicin, performed for one cycle, was administrated during the early third trimester of pregnancy. Septic shock occurred due to severe myelosuppression. An emergent cesarean section was performed in response to a nonreassuring pattern of the fetal heart rate and a rapid decrease in fetal amniotic fluid. The neonate delivered at 32 weeks' gestation showed no signs of cardiac failure but did show signs of transient myelosuppression, hepatopathy, and elevated creatine kinase. Complete remission was established with idarubicin including chemotherapy.
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PMID:Idarubicin administered during pregnancy: its effects on the fetus. 1525 24

Mitoxantrone (MTZ) has been shown to be effective in the treatment of newly diagnosed acute myeloblastic leukemia (AML). The objective of this randomized study was to evaluate the impact of mode of administration of MTZ on the response and recurrence rates in newly diagnosed patients with AML and to compare the toxicity patterns associated with bolus and continuous infusion (CI) of MTZ. From March 1987 to March 1994, 40 newly diagnosed patients with AML were randomized to receive either bolus or CI-MTZ, administered for 3 days at 10 mg/m2/day in combination with CI-cytarabine for 7 days at 100 mg/m2/day. Patients achieving complete remission (CR) received two consolidation cycles followed by monthly maintenance cycles, aiming a total of 12 cycles of chemotherapy. Fifteen patients (75%) in the bolus arm and 16 patients (80%) in the CI arm achieved CR. There were no significant differences in rates of early death and time to myeloid recovery between the two groups. After 11 years from the initiation of the study, median disease-free survival (DFS) in bolus and CI groups were 19 and 29 months after a median follow-up of 10 and 14 months, respectively. DFS rates at 10 years were 16.7% in the bolus group and 28.6% in the CI group (p = 0.36). Overall survival (OS) rates during the same period were 10.7 and 21.3% in the bolus and CI groups, respectively (p = 0.26). No relapse was observed in either group after 4 years. In patients younger than 40 years of age, DFS and OS were found to be significantly longer in the CI arm (p = 0.02 and p = 0.03, respectively). Mild asymptomatic cardiotoxicity associated with a decrease of 10 to 20% in the ejection fraction occurred in a patient in CI-MTZ arm and in two patients in the bolus arm. None of these patients showed any evidence of cardiac failure during their subsequent follow-up. Grade III-IV alopecia (p = 0.05) and grade I-II hepatotoxicity (p = 0.01) were more frequent in the CI arm. A tendency for higher frequency of grade III-IV nausea was observed in the bolus arm (9 vs. 3%, p = 0.10). As a conclusion, bolus and CI administration of MTZ were equally effective and tolerated well. Development of new anti-leukemia agents with novel treatment approaches is still needed to improve the high relapse rates in patients with AML who do not have an HLA-matched donor.
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PMID:A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia. 1538 63

Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) receptors. Separate cohorts of patients received SU11248 for 4-week cycles followed by either a 2- or a 1-week rest period. At the starting dose level of 50 mg (n = 13), no dose-limiting toxicities were observed. The most frequent grade 2 toxicities were edema, fatigue, and oral ulcerations. Two fatal bleedings possibly related to the disease, one from a concomitant lung cancer and one cerebral bleeding, were observed. At the 75 mg dose level (n = 2), one case each of grade 4 fatigue, hypertension, and cardiac failure was observed, and this dose level was abandoned. All patients with FLT3 mutations (n = 4) had morphologic or partial responses compared with 2 of 10 evaluable patients with wild-type FLT3. Responses, although longer in patients with mutated FLT3, were of short duration. Reductions of cellularity and numbers of Ki-67(+), phospho-Kit(+), phospho-kinase domain-containing receptor-positive (phospho-KDR(+)), phospho-signal transducer and activator of transcription 5-positive (phospho-STAT5(+)), and phospho-Akt(+) cells were detected in bone marrow histology analysis. In summary, monotherapy with SU11248 induced partial remissions of short duration in acute myeloid leukemia (AML) patients. Further evaluation of this compound, for example in combination with chemotherapy, is warranted.
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PMID:A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. 1545 12

Infective endocarditis (IE) caused by microbial infection is virtually always fatal if untreated. High-dose and long-term antibiotic treatment is required to eradicate microorganisms. If increased risk of embolic events, persistent infection, and progressive cardiac failure are present, surgery is indicated. However, surgery can carry an increased risk of mortality and morbidity in critically ill children of whom other treatment options such as administering, a thrombolytic agent; recombinant tissue plasminogen activator (r-tPA) could be an alternative choice. Here, we report a 14-year-old male with Down syndrome and acute myeloblastic leukemia, diagnosed with IE characterized by two large vegetations on aortic and mitral valves, who was successfully treated with r-tPA.
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PMID:Treatment of infective endocarditis with recombinant tissue plasminogen activator. 1671 1


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