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)

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.
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PMID:Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma. 1176 12

Conventional cytotoxic therapy of hematologic malignancies is often associated with significant morbidity. This morbidity is often due to the lack of specificity for hematopoietic cells. Therefore, the concept of targeted therapy for patients with hematologic malignancies has received attention for many years. The goal of monoclonal antibody therapy is to target specific cell surface antigens on malignant hematopoietic cells, while sparing normal cells and tissues. Currently, monoclonal antibodies are being evaluated for their cytotoxic effects as well as their ability to deliver toxic agents or radiation. Rituximab, a chimeric anti-CD20 antibody, has shown response rates of approximately 50% with minimal toxicity in patients with refractory indolent lymphoma. Campath-1H (anti-CD52) has shown encouraging results in patients previously treated for chronic lymphocytic leukemia, with response rates up to 33%, although with significant toxicity. Anti-CD33 antibodies are being used to deliver cytotoxic agents, such as calicheamicin to patients with acute myeloid leukemia with response rates up to 30%. In addition, anti-CD33 and anti-CD45 antibodies have been used to deliver radiation directly to leukemic cells. (131)I-labeled anti-CD45 antibodies are being studied in combination with conventional preparative regimens in patients receiving bone marrow transplantation. Lastly, the therapeutic agent STI571 (signal transduction inhibitor 571) has demonstrated the capability of targeting specific molecular abnormalities seen in hematologic malignancies. STI571 targets the tyrosine kinase activity of the bcr-abl fusion protein seen in chronic myeloid leukemia. STI571 has induced complete hematologic responses in up to 98% of patients evaluated in clinical trials.
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PMID:Cell surface antigen and molecular targeting in the treatment of hematologic malignancies. 1200 80

Treatment of patients with unconjugated MAb such as rituximab (Rituxan) the anti-CD20 MAb or trastuzumab (Herceptin) the anti-Her2 MAb, have shown efficacy in clinical trials and have gained approval from the Food and Drug Administration (FDA) has a result. Likewise, an anti-CD33 MAb conjugated with the antibiotic calicheamicin (Mylotarg) has proven efficacious in the treatment of patients with acute myeloid leukemia and has also been approved by the FDA. This overview presents some of the monoclonal antibody (MAb)-guided strategies with a focus on some of the experiences reported for MAb evaluated in clinical trials.
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PMID:Monoclonal antibody-based therapy strategies: providing options for the cancer patient. 1217 46

Of 12 patients with relapsed CD20(+) B-cell non-Hodgkin's lymphoma (B-NHL) enrolled in a phase I study of rituximab, 11 were eligible, and of these 2 achieved a complete response and 5 a partial response. The elimination half-life of rituximab was 445+/-361 h, and serum rituximab levels were detectable at 3 months. In a phase II study, 90 patients with relapsed indolent B-NHL or mantle cell lymphoma (MCL) were treated with infusions of rituximab 375 mg/m(2) once weekly for four doses. The overall response rate in indolent B-NHL and MCL was 61% (37/61, 95% CI 47-73%) and 46% (6/13, 95% CI 19-75%), respectively. The median progression-free survival (PFS) was shorter in MCL patients, in those with extranodal disease, and in those who had received two or more prior chemotherapy regimens ( P<0.01). Rituximab retreatment was well tolerated in 13 patients with relapsed indolent B-NHL and there were no grade 3/4 nonhematologic toxicities. Partial response was observed in five (38%, 95% CI 14-68%) patients, and the median PFS after retreatment was 5.1 months. In a single-agent phase II study of infusions of rituximab 375 mg/m(2) once weekly for eight doses against relapsed aggressive B-NHL showed, 21 (37%, 95% CI 24-51%) of the 57 eligible patients responded. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL with acceptable toxicities. Yttrium-90 provides advantages over iodine-131 because it delivers higher beta energy. In 2002, we initiated a feasibility study of yttrium-90-labeled ibritumomab tiuxetan for relapsed indolent B-NHL in Japan. Gemtuzumab ozogamicin (CMA-676) is a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody. Of 20 patients with relapsed or refractory acute myeloid leukemia enrolled in a "bridging" phase I/II study, 7 showed an objective response. It is concluded that monoclonal antibodies will have play a significant role in the treatment of hematologic malignancies in the future.
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PMID:Monoclonal antibodies for the treatment of hematologic malignancies: clinical trials in Japan. 1281 34

Monoclonal antibodies used in the treatment of cancer are discussed. Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can carry substances, such as radioactive isotopes, toxins, and antineoplastic agents, to the targeted cells. Five monoclonal antibodies--rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, and ibritumomab tiuxetan--are available for clinical use. Rituximab is active against indolent lymphomas, providing a valuable alternative for patients with relapsed or refractory disease. Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) increased survival over CHOP alone in patients with high-grade lymphomas. Trastuzumab has significant activity against HER-2-positive breast cancer, especially in combination with paclitaxel or an anthracycline and cyclophosphamide. Gemtuzumab ozogamicin is an active second-line therapy in older patients with acute myelogenous leukemia, but its role in combination regimens is unclear. Alemtuzumab is a valuable option for salvage therapy of patients with chronic lymphocytic leukemia. Ibritumomab tiuxetan delivers radioactive isotopes to tumor cells and is active against indolent lymphomas in patients who have relapsed after chemotherapy or rituximab therapy. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumor lysis syndrome, arrhythmias, and pulmonary dysfunction. Alemtuzumab causes immunosuppression, increasing the risk of infection. Gemtuzumab ozogamicin may cause hepatotoxicity, and trastuzumab may cause significant pulmonary or cardiac toxicity. Investigational monoclonal antibodies include edrecolomab and tositumomab. Monoclonal antibodies have a significant role in the management of patients with advanced refractory or relapsed lymphomas and leukemias.
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PMID:Monoclonal antibodies in the treatment of cancer, Part 1. 1295 53

Monoclonal antibodies used in the treatment of cancer are discussed. Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can carry substances, such as radioactive isotopes, toxins, and antineoplastic agents, to the targeted cells. Five monoclonal antibodies--rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, and ibritumomab tiuxetan--are available for clinical use. Rituximab is active against indolent lymphomas, providing a valuable alternative for patients with relapsed or refractory disease. Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) increased survival over CHOP alone in patients with high-grade lymphomas. Trastuzumab has significant activity against HER-2-positive breast cancer, especially in combination with paclitaxel or an anthracycline and cyclophosphamide. Gemtuzumab ozogamicin is an active second-line therapy in older patients with acute myelogenous leukemia, but its role in combination regimens is unclear. Alemtuzumab is a valuable option for salvage therapy of patients with chronic lymphocytic leukemia. Ibritumomab tiuxetan delivers radioactive isotopes to tumor cells and is active against indolent lymphomas in patients who have relapsed after chemotherapy or rituximab therapy. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumor lysis syndrome, arrhythmias, and pulmonary dysfunction. Alemtuzumab causes immunosuppression, increasing the risk of infection. Gemtuzumab ozogamicin may cause hepatotoxicity, and trastuzumab may cause significant pulmonary or cardiac toxicity. Investigational monoclonal antibodies include edrecolomab and tositumomab. Monoclonal antibodies have a significant role in the management of patients with advanced refractory or relapsed lymphomas and leukemias.
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PMID:Monoclonal antibodies in the treatment of cancer, Part 2. 1296 6

Treatment of patients with therapeutic monoclonal antibodies (mAbs) such as rituximab (Rituxan), an anti-CD20 mAb, or trastuzumab (Herceptin), an anti-HER2 mAb, have shown efficacy in clinical trials and have gained approval from the Food and Drug Administration (FDA). Mylotarg, an anti-CD33 mAb conjugated with the antibiotic calicheamicin has proven efficacious in the treatment of patients with acute myeloid leukemia and has also received FDA approval. However, the use of radionuclides to either augment inherent activity or to exploit the specific targeting properties has been a major development in mAb therapeutics. Radionuclide- bearing mAbs have recently been approved by the FDA; Zevalin, an anti-CD20 mAb armed with (90)Y and Bexxar, an anti-CD20 mAb armed with (131)I. This overview presents some background and some of the strategies pertaining to radiolabeled monoclonal antibody therapies with a focus on experiences reported for radiolabeled mAbs as evaluated in clinical trials.
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PMID:Targeting of radio-isotopes for cancer therapy. 1497 24

A regimen combining fludarabine, cyclophosphamide and mitoxantrone (FCM) was used to treat 29 patients with relapsed or refractory chronic lymphocytic leukemia (CLL, N = 24) and low-grade non-Hodgkin's lymphoma (NHL, N = 5) based on evidence suggesting synergism between the 3 drugs. Patients were treated with mitoxantrone 5mg/m2 i.v. day 1 only, fludarabine 25 mg/m2 i.v. for 3 days or 24 mg/m2 orally for 5 days, cyclophosphamide 250 mg/m2 i.v. for 3 days or 150 mg/m2 orally for 5 days inclusive. Eighteen patients had previously received fludarabine and most were heavily pretreated with 40% having >2 prior treatments. A median number of 4 FCM courses (range of 1-9) were given. The response rate was 78.5%: 32% complete remission, 25% nodular partial remission, 21.5%, partial remission. Median duration of response was 19 months and median survival was 42 months. Sixteen patients (57%) developed neutropenia to < 0.5 x 10(9)/l and 12 (43%) infectious complications. Four patients developed large cell lymphoma (Richter's syndrome) and 2 acute myeloid leukemia. FCM is a useful combination for relapsed or refractory CLL and low grade NHL with high response rates and long duration of response. The role of FCM as first line therapy deserves study as well as its combination with the monoclonal antibody Rituximab.
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PMID:Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma. 1529 53

Monoclonal antibodies (mAbs) therapies have been introduced to the many kinds of malignancies. Rituximab (Rituxan), a chimeric anti-CD20 monoclonal antibody, has improved clinical outcome in the patients with B cell non-Hodgkin's lymphoma (NHL) as a single agent as well as combination with chemotherapies including CHOP and stem cell transplantation. The efficacy has been reported in the patients with follicular lymphoma as well as aggressive NHL. The expression of CD20 should be confirmed by immunopathological staining or flow cytometry before the treatment. Gemtuzumab ozogamicin (Mylotarg), calicheamicin conjugates of anti-CD33 mAb, has been introduced in the treatment of AML. CD33 is not expressed by immature pluripotent stem cells even though expressed on myeloid progenitor cells. Mylotarg is internalized via CD33, however, detouched calicheamicin might be pumped out by multi-drug resistant related p glycoprotains (p-gp). The expression of CD33 and p-gp should be analyzed by flow cytometry before the treatment. We should give another caution to tumor-lysis syndrome and veno-occlusive disease.
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PMID:[Monoclonal antibody therapy and laboratory medicine]. 1565 71

One of the important approaches for further prolonging remission duration and eradicating minimal residual disease in acute leukemia is immunotherapy. Four kinds of immunotherapy for acute leukemia are under investigation: (1) monoclonal antibodies, among them, Mylotarg (cytotoxic antibiotic calicheamicin linked to CD33 Mab) is given for the treatment of refractory or relapsed acute myeloid leukemia and molecular relapse in acute promyelocytic leukemia with good results, Campath-1H (antiCD52 Mab) is administered in the treatment of prolymphocytic leukemia and Rituximab (anti-CD20 Mab) in B-PLL with high complete remission rates. Other Mabs under preclinical and clinical trials include anti-IL-2 receptor Mab for the treatment of acute T lymphocytic leukemia, anti-220 kD Mab-6G7 for acute leukemias, recombinant immune toxin BL22 (anti-CD22) for hairy cell leukemia and Mabs labeled with radio-isotopes for different types of acute leukemias; (2) adoptive cellular immunotherapy using cytokine-induced killer cell, alloreactive NK cells, allogeneic or autologous leukemic-specific CD8(+) cytotoxic T lymphocytes, and other immune effector cells; (3) cytokines and other immune modulators comprising IL-2, IL-12, GM-CSF, CD40L, FLT-3L and thalidomide and its derivatives; (4) leukemia vaccines of several different formulations including antigen-specific, leukemia cell-based, leukemia antigen-pulsed dendritic cell (DC) and leukemia-derived DC vaccines, the latter two formulations are more attractive. In conclusion, up to now, the most effective example of immunotherapy in acute leukemia is provided by the administration of Mabs, and the majority of other approaches in immunotherapy for acute leukemia although promising, need further studies.
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PMID:[Present status in studying immunotherapy for acute leukemia and its perspective--Editorial]. 1585 71


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