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)

Quality of life (QL) was evaluated in 101 patients with AML undergoing intensive and prolonged treatment at 12 sequential time points by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 questionnaire and the profile of mood states scale (POMS). For those patients having completed the course of inpatient treatment (n=37), QL improved from the beginning of chemotherapy to the end of inpatient treatment. Patients who subsequently went off protocol did not differ significantly in their self-assessed QL when compared with patients who completed therapy. Fatigue was more closely related to QL than nausea/emesis or appetite loss, but did not correlate with hemoglobin levels.
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PMID:Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia. 1183 78

Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells that express CD33 by means of a humanized anti-CD33 monoclonal antibody conjugated to a modified antitumor antibiotic, calicheamicin. The effects of gemtuzumab ozogamicin (given intravenously at a dose of 9 mg/m2 for 2 doses separated by 2 weeks) have been evaluated in 3 phase II studies involving patients (n = 188) with acute myeloid leukemia (AML) in first relapse. Interim analysis has revealed that 30% of patients achieved remission, characterized by < or = 5% blasts in the marrow, neutrophil count > or = 1500/microL, hemoglobin > or = 9 g/dL, and independence from red blood cell and platelet transfusion. Grade 3/4 acute toxicities included nausea or vomiting (11%); elevated serum aminotransferase enzyme (16%) and bilirubin (26%) levels; and infusion-related chills (9%), fever (6%), and hypotension (5%). As predicted with CD33-targeted therapy, most patients had neutropenia (98%) and thrombocytopenia (99%). However, the incidence of grade 3/4 bleeding events (14%) and infection rates (pneumonia, 7%; sepsis, 15%) was low. No patients were reported to have treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Veno-occlusive disease (VOD) after gemtuzumab ozogamicin treatment (but prior to other therapies) occurred in 2% of patients (4/188), and the VOD-related death rate was < 1% (1/188). Prior hematopoietic stem cell transplant may be a risk factor for VOD (P = 0.002, univariate analysis). Gemtuzumab ozogamicin is a safe and effective treatment in carefully selected patients with AML in first relapse.
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PMID:Acute and long-term toxicities associated with gemtuzumab ozogamicin (Mylotarg) therapy of acute myeloid leukemia. 1197 Jul 68

Overexpression of Bcl-2 is a potential mechanism for chemoresistance in acute leukemia and has been associated with unfavorable clinical outcome. We hypothesized that down-regulation of Bcl-2 would restore chemosensitivity in leukemic cells. To test this hypothesis, we performed a phase 1 study of G3139 (Genasense, Genta, Berkeley Heights, NJ), an 18-mer phosphorothioate Bcl-2 antisense, with fludarabine (FL), cytarabine (ARA-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) salvage chemotherapy in patients with refractory or relapsed acute leukemia. Twenty patients with refractory or relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. G3139 was delivered by continuous infusion on days 1 to 10. FLAG chemotherapy was administered on days 5 to 10. Common side effects of this combination included fever, nausea, emesis, electrolyte imbalance, and fluid retention that were not dose limiting. Plasma pharmacokinetics of G3139 demonstrated steady-state concentration (Css) within 24 hours. Of the 20 patients, 9 (45%) had disease response, 6 (5 AML, 1 ALL) with complete remission (CR) and 3 (2 AML and 1 ALL) with no evidence of disease but failure to recover normal neutrophil and/or platelet counts or to remain in remission for at least 30 days (incomplete remission). Bcl-2 mRNA levels were down-regulated in 9 of the 12 (75%) evaluable patients. This study demonstrates that G3139 can be administered safely with FLAG chemotherapy and down-regulate its target, Bcl-2. The encouraging clinical and laboratory results justify the current plans for a phase 3 study in previously untreated high-risk AML (ie, age at least 60 years).
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PMID:Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia. 1239 93

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

HuM195 is a humanized, unconjugated, anti-CD33 monoclonal antibody. Fifty adult patients with relapsed or refractory AML were randomized to receive HuM195 at a dose of 12 or 36 mg/m(2) by intravenous infusion over 4 h on days 1-4 and 15-18. Patients with stable or responding disease received two additional cycles on days 29-32 and 43-46. HuM195 was given as first salvage therapy in 24 patients and as second or subsequent salvage therapy in 26 patients. Pretreatment blast percentage in the marrow was between 5 and 30% in 20 patients with the others having blast counts greater than 30%. The median age of patients was 62 years (range 26-86) and CD33 was detected in 95% of patients for whom immunophenotyping was available. Of 49 evaluable patients, two complete and one partial remission were observed. All three responses were in patients treated at the 12 mg/m(2) dose level and all had baseline blast percentages less than 30%. Decreases in blast counts ranging from 30 to 74% were seen in nine additional patients. Infusion-related events of fever and chills occurred in the majority of patients and were generally mild and primarily related to the first dose of antibody. No hepatic, renal or cardiac toxicities were observed and other adverse events such as nausea, vomiting, mucositis and diarrhea were uncommon or felt to be unrelated to HuM195. In addition, anti-HuM195 responses were not detected. HuM195 as a single agent has minimal, but observable, anti-leukemic activity in patients with relapsed or refractory AML and activity is confined to patients with low burden disease. No significant differences in clinical efficacy or toxicity were seen between the two dose levels of antibody. HuM195 was well tolerated with infusion-related fevers and chills the predominant toxicities seen. Meaningful clinical efficacy of this unconjugated monoclonal antibody may be realized only in patients with minimal residual disease, or in combination with chemotherapy.
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PMID:Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. 1259 28

The compound CMB-401 is an immunoconjugate consisting of the monoclonal antibody (MAb) hCTM01 directed against polymorphic epithelial mucin covalently bound to the cytotoxic antibiotic calicheamicin by an amide linker. We evaluated CMB-401 as monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian carcinoma (EOC). Twenty-one 21 women aged 38 to 80 years with recurrent EOC (recurrence >6 months after initial platinum-containing chemotherapy) were enrolled. Tumor response and serum cancer antigen 125 (CA125) levels were assessed before and after active treatment. After an initial intravenous (i.v.) dose of hCTM01 (without calicheamicin), the calicheamicin-linked CMB-401 (16 mg/m(2 ) i.v.) was administered over 60 min for up to 7 cycles, with 4 weeks between cycles. Nineteen patients were evaluable. Measurable changes observed following administration of CMB-401 did not meet the criteria for partial remission (PR). CMB-401 was not effective as monotherapy for this type of EOC. Adverse events experienced by patients in the study included nausea (95%), asthenia (90%), abdominal pain (62%), headache (57%), anorexia (57%), and diarrhea (57%), mostly at a toxicity grade level of 1 or 2. Based on published efficacy of conjugates that deliver calicheamicin via hybrid (bifunctional) linkers [e.g. gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia], we hypothesize that the amide linker used in CMB-401 may have contributed to its failure to induce PR in patients in this study. Use of hybrid linkers to target hCTM01 or other antibodies to EOC may warrant further investigation.
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PMID:A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma. 1266 49

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

Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of leukemic blasts. This concept represented the rationale for the initiation of a multicenter phase 2 trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor, and fms-like tyrosine kinase-3 (FLT3) in patients with advanced AML. Entered into the study were 43 patients with refractory AML or elderly patients not judged medically fit for intensive induction chemotherapy; 42 patients received at least one dose of study drug. Treatment was generally well tolerated, with nausea, headache, and bone pain the most frequent treatment-related side effects. One patient had a morphologic remission (French-American-British [FAB] criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. There were 7 patients who achieved a partial response (reduction of blasts by at least 50% in bone marrow and peripheral blood) lasting 1 to 5 months. Patients with AML blasts expressing high levels of VEGF mRNA by quantitative polymerase chain reaction (PCR) had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the antiangiogenic effects of SU5416.
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PMID:A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. 1284 1

We describe a case of Acanthamoeba encephalitis in a 45-year-old Caucasian male with acute myelogenous leukemia, who was 140 days status post partially mismatched related donor peripheral blood stem cell transplant. The patient had been transplanted with a highly T-cell-depleted graft, and was not taking any immunosuppressive drugs, and had no history of graft-versus-host disease. He complained of nausea, vomiting, and occasional episodes of confusion; he also had a chronic cough since transplantation. Physical examination was unremarkable except for orthostatic hypotension. Neurologic examination was within normal limits. Laboratory values including electrolytes, white blood cells and platelet counts were normal. Computed tomographic scan of the brain showed a pansinusitis and a hyperdense lesion along the corona radiata suggestive of a fungal abscess. Magnetic resonance imaging showed multifocal areas with mass effect in the posterior fossa and parietal and occipital lobes. The patient had worsening respiratory failure and died three days after admission. At autopsy, specific immunofluorescent staining identified Acanthamoeba castellani in the brain and lungs.
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PMID:Acanthamoeba castellani encephalitis following partially mismatched related donor peripheral stem cell transplantation. 1498 4

From 1998 to 2001, 5 consecutive cases of AML/TMDS entered our hospital and achieved complete remission (CR) with continuous drip infusion of low-dose etoposide and low-dose Ara-C combined with mitoxantrone (MEtA regimen). The ages of the 5 patients (4 males and 1 female) ranged 32 to 50 years-old, respectively. WBCs were 1,560-45,150/microl, blasts were 12-62%. Bone marrow aspirates revealed trilineage myelodysplasia with various number of blasts. These patients had an acute onset and no preceding hematologic disorders. They were diagnosed M2/TMDS or M4/TMDS. Continuous drip infusion of etoposide (50 mg/body/day) and Ara-C (30 mg/body/day) were given for 11-14 days and a bolus injection of mitoxantrone (8 mg/m2) was added for 2-3 days. Patient 5 was given additional MIT (6.7 mg/m2 on day 6). All cases achieved CR in 21-24 days after the end of the therapy. Toxicities were nausea, vomiting, stomatitis, alopecia and fever due to infection. All were well tolerable, however. Two patients are alive more than 4 years without relapse. MEtA regimen is available for AML/TMDS.
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PMID:[Five cases of de novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) achieved CR with the continuous drip infusion of low-dose etoposide and low-dose cytosine arabinoside combined with mitoxantrone (MEtA)]. 1527 98


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