Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia, a decreased oxygen-carrying capacity of the blood, develops frequently in patients with end-stage renal disease (ESRD) or cancer. Given the wide variation in clinical response to erythropoietin in the treatment of anemia associated with these diseases, 2 meta-analyses of its effectiveness were undertaken. Databases (MEDLINE and International Pharmaceutical Abstracts) were searched to identify relevant articles. Search terms included erythropoietin, anemia, end-stage renal disease, cancer, multiple myeloma, and myelodysplastic syndrome. Searches were limited to human subjects and the English language. Reference lists of identified articles were reviewed for further articles of interest. The primary author (W.A.M.) selected the articles, and 2 researchers, working independently, extracted the necessary data. Articles had to meet the following criteria to be included in the meta-analyses: (1) Articles must have dealt with treatment of subjects with documented anemia. (2) Studies must have been original research with sample size > or =10. (3) Abstracts could be included if the full research manuscript was unavailable. (4) Patients could not be concurrently receiving other growth factors. (5) The quality of the selected articles must have been assessed by 2 independent researchers. A clinical response to erythropoietin was defined as a 0.06 increase in hematocrit or a 20 g/L increase in hemoglobin. Thirty-nine of the 76 identified articles were included in the meta-analyses. The effectiveness of erythropoietin was calculated at 87% for ESRD, 79% for multiple myeloma, 40% for solid tumor cancer, and 13% for myelodysplastic syndrome. Both subgroup and sensitivity analyses were performed.
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PMID:Meta-analyses of the effectiveness of erythropoietin for end-stage renal disease and cancer. 1050 43

Cisplatin appears to be the major cause for long-term toxicity in patients treated for testicular cancer. Long-term side effects consist mainly of nephrotoxicity, ototoxicity, and neurotoxicity as well as gonadal damage. Following standard-dose chemotherapy approximately 20% to 30% of patients will be affected by long-term side effects, although not all these side effects will cause an impaired quality of life. Several strategies have been or currently are being evaluated to reduce acute and long-term complications including the introduction of equally effective, but less toxic regimens, or the use of cytoprotective agents such as amifostine. Secondary acute myeloid leukemia and secondary myelodysplastic syndrome probably represent the worst possible long-term complications of cancer therapy in those patients who originally were cured of their primary testicular cancer. Therapy-related solid tumors are mainly associated with the use of radiation therapy and the risk for developing a therapy-related solid tumor is increased approximately two to three times compared to the general population. In contrast, therapy-related leukemias are predominantly associated with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia following treatment of germ cell cancer is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses< or = 2 g/m(2) and >2 g/m(2), respectively. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related long-term complications should encourage the search for equally effective but less toxic therapies. This review will highlight important available data about therapy-related toxicity and particularly, therapy-related malignancies following cisplatin-etoposide-based chemotherapy.
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PMID:Late toxicity following curative treatment of testicular cancer. 1058 57

Given the young age at which testicular cancer is treated and the excellent prognosis for patients suffering from this disease, therapy-related malignancies represent a significant problem. Therapy-related solid tumors are associated mainly with the use of radiation therapy. The risk for developing a therapy-related solid tumor is approximately 2- to 3-fold increased compared with the general population. Therapy-related leukemias are associated predominantly with chemotherapy, particularly with the use of topoisomerase-II inhibitors and alkylating agents. In general, the cumulative incidence of therapy-related leukemia is low. It is approximately 0.5% and 2% at 5 years of median follow-up for patients receiving etoposide at cumulative doses < or = 2 g/m2 and > 2 g/m2, respectively. High cumulative doses of etoposide given over a short period of time appear to be less leukemogenic than a similar dose of etoposide given over a longer period of time. There might, additionally, be a synergistic effect of cisplatin and etoposide on the induction of therapy-related leukemia. For patients who receive high-dose chemotherapy with autologous stem-cell support, the risk of therapy-related myelodysplastic syndrome and leukemia appears to be substantially lower compared with that reported in non-Hodgkin's lymphoma patients undergoing high-dose chemotherapy. The transplantation procedure itself does not appear to add to the therapy-related leukemia risk. The risk-benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high-dose chemotherapy. However, even the acceptably low number of therapy-related leukemias should encourage the search for equally effective but less toxic therapies.
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PMID:Therapy-related malignancies following treatment of germ cell cancer. 1059 12

Recent progress in the treatment of aplastic anemia has dramatically changed the previously grim prognosis for these patients. Improvements in bone marrow transplantation and immunosuppression have increased the number of long-term survivors so that immediate survival is no longer the sole concern. Here, we review the major clinical studies and summarize recent analyses of risk factors for developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), acute leukemia, or solid tumor after treatment for aplastic anemia. We also examine biologic clues that may shed light on the interrelationship between aplastic anemia and clonal diseases.
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PMID:Late clonal diseases of treated aplastic anemia. 1067 14

In a previous study, we evaluated efficacy of repeated antilymphocyte globulin (ALG) treatment for patients with severe aplastic anemia not responding to an initial ALG treatment or relapsing after initial response to ALG. We now searched in the same cohort of patients for differences between patients who responded to treatment and remained free of complications and those who relapsed or developed a clonal complication. From 107 patients surviving for more than 1 year after immunosuppression, 34 remained free from complications after the first course of ALG, and 73 presented an event defined as relapse of aplastic anemia, development of a clonal complication such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome or leukemia, or appearance of a solid tumor. We compared these two groups for survival, clinical performance and blood counts during follow-up. Survival probability was 93% for the event-free patients, and 55% for the patients with a complication event (p = 0.0003). Event-free patients had a higher incidence of complete remission (71%), were more often free of immunosuppressive treatment (79%) and independent of transfusions (100%), and had a higher Karnofsky score (91% with a score > or =90%) as compared to the group with events (29, 37, 67, 48%; p < or = 0.0002). At 1 and 3 years, event-free patients had significantly higher leukocyte and neutrophil counts, as compared to patients with a complication (p < 0.05). However, at 3 and 5 years, event-free patients had borderline higher platelet counts (p = 0.056, p = 0.078) and hemoglobin (p = 0. 097, p = 0.061). The coefficient of variation as an expression of the variability of the results in each group was systematically lower at 3, 5 and 10 years in the group of event-free patients. Despite some differences between the two groups, our data support the hypothesis that patients with long-lasting remissions should not be considered as definitively cured of aplastic anemia.
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PMID:Predictive factors for cure after immunosuppressive therapy of aplastic anemia. 1070 60

Fever is frequently the only clinical sign of infection in patients with chemo-induced neutropenia. In this setting, empirical administration of broad spectrum antibiotics must be rapid. The aim of this work was to compare, for the first time, cefpirome (CPO) and piperacillin-tazobactam (PT) in a large randomized trial. Two hundred-eight febrile neutropenic episodes (FNE) (> or = 38.5 degrees C and ANC < or = 0.5 giga/l) were treated by randomization, as first line therapy, using either CPO 2 g x 2/day (105 cases) or PT 4 g x 3/day (103 cases), alone (CPO: 15/PT: 15), or plus aminoglycoside (165 cases, CPO: 82/PT: 83) or quinolone (CPO: 2/PT: 2). There were 131 men and 77 women aged between 17 and 83 years (median: 49) who received chemotherapy (n = 160) or allogeneic (n = 10) or autologous (n = 38) stem cell transplantations. Underlying diseases were: acute leukemia (n = 131), lymphoma (n = 33), myeloma (n = 16), solid tumor (n = 8), myeloproliferative disorder (n = 9), chronic lymphoid leukemia (n = 5), aplastic anemia (n = 3), myelodysplasia (n = 3). Distribution of age, neutropenia duration (median: 17 days), underlying disease, and protocol therapy duration (median: 11 days) was comparable in both arms. A microbiologically documented infection (MDI) was evidenced in 57 cases (27%). Bacteria were isolated from blood cultures in 54 cases (Gram positive: 32 cases). Their in vitro susceptibility rates to CPO and PT were not different. Two days after antibiotics initiation, clinical (fever disappearance) and microbiological (culture negativation) success rates (SR) were 62% for CPO versus 61% for PT and 50% versus 55% respectively in case of MDI (p = 0.89). Two deaths and 77 failures were registered. At the end of protocol, SR (no antibiotic change/absence of superinfection) was 59% with CPO versus 50% with PT (p = 0.27) and 53% versus 40% respectively in the 151 cases with neutropenia > or = 10 days (p = 0.17). The occurrence of side effects was similar in both arms. In our hands, the efficacy of CPO and PT was comparable for treating FNE.
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PMID:A randomized prospective multicentre trial of cefpirome versus piperacillin-tazobactam in febrile neutropenia. 1169 2

Post-treatment surveillance in non-Hodgkin's lymphoma is required for an early diagnosis of a relapse and for the detection of a potential late treatment-related complication. The risk of relapse is highest during the first 2 years in aggressive lymphomas. The risk of relapse decreases then and becomes very low after the 5th year of follow-up. For low-grade lymphomas, the relapse rate remains constant for a longer period and late relapses are more common. Clinical examination and biological tests (blood cell count, lactate dehydrogenase and, in some instance, beta-2-microglobulin serum level determination) are the basis of the surveillance. Radiological and specific tests will be done according to the initial organ involvement. The frequency of the surveillance mainly depends on the histological subtype. Late chemotherapy-related complications include second cancer (solid tumor, myelodysplastic syndrome and acute leukemia), cardiac and endocrine toxicity. Detection of these events also requires close clinical and biological monitoring.
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PMID:[Post-therapy surveillance in non-Hodgkin's lymphomas]. 1206 66

Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. The etiology is diverse, and malignancy, especially hematopoietic in origin, is the most common underlying disease of BMN. In this retrospective analysis, cases with BMN were re-evaluated for etiology, histopathologic details, and clinical manifestations. In the last 8 years, 23 cases of BMN were detected among the 1,083 bone marrow (BM) biopsies, and the prevalence was found to be 2.2%. Three of these 23 cases with BMN were children, and 20 cases were in adults. Sixteen of these cases (80%) had underlying malignant disease, and four (20%) had nonmalignant disease. Among the malignant cases, three cases had acute myeloblastic leukemia (AML), four had relapsed Hodgkin's disease (R-HD), one had acute lymphoblastic leukemia (ALL), two had chronic myelocytic leukemia (CML), two had non-Hodgkin's lymphoma (NHL), three had disseminated intravascular coagulation (DIC) associated with metastatic solid tumor, and one had myelodysplastic syndrome/myeloproliferative syndrome (MDS/MPS). Among the nonmalignant cases, two had tuberculosis infection, one had anti-phospholipid syndrome (APS), and one had a history of drug ingestion. The most common symptoms were bone pain, fever, fatigue, and jaundice. The most common laboratory findings were variable and associated with underlying disease, but anemia, leukopenia, thrombocytopenia, and high LDH and alkaline phosphatase levels were detected in the majority of the cases, as was also seen in other series. BMN was graded according to the extent of necrosis in the BM biopsy, and necrosis was extensive in 12 cases, moderate in five cases, and mild in three cases. Increased reticulin was found in 16 cases; four cases had severe, eight had moderate, and four had mild fibrosis, and this was found to be an interesting accompanying finding in BMN. In conclusion malignancy is the most common cause of BMN but some nonmalignant conditions such as tuberculosis and APS may be the underlying cause of BMN.
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PMID:Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the literature. 1221 Aug 11

The Wilms tumor gene WT1 is expressed in leukemias and various kinds of solid tumors, including lung and breast cancer, and exerts an oncogenic function in these malignancies, suggesting that WT1 protein is a novel, overexpressed tumor antigen. The WT1 protein, in fact, is an attractive tumor rejection antigen in animal models. Stimulation in vitro of peripheral blood mononuclear cells with HLA-A*2402--and HLA-A*0201--restricted 9-mer WT1 peptides elicits WT1-specific cytotoxic T-lymphocytes (CTLs), and the CTLs kill endogenously WT1-expressing leukemia or solid tumor cells. Furthermore, WT1 immunoglobulin M (IgM) and IgG antibodies are detected in patients with hematopoietic malignancies such as acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndromes, indicating that WT1 protein overexpressed by leukemia cells is indeed immunogenic. Taken together, these results demonstrate that WT1 protein is a promising tumor antigen for cancer immunotherapy against leukemias and various kinds of solid tumors, including lung and breast cancer.
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PMID:Cancer immunotherapy targeting WT1 protein. 1221 10

To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P<0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P<0.001, 8.1 (2.2-20.7) P=0.002 and 1.98 (1.1-3.2) P=0.009, respectively. In multivariate analysis, age >or=35 years at the time of AHSCT (P=0.001) and an interval from diagnosis to AHSCT >or=36 months (P=0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.
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PMID:Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis. 1456 93


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