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

Idarubicin is a new derivative of Daunorubicin which was found to be more potent and more active than Daunorubicin and Doxorubicin in several experimental leukemias. Its antileukemic activity in preclinical models prompted the introduction of Idarubicin into clinical studies. As a single agent, Idarubicin produced complete remission in 20% and 30% of patients with heavily pretreated pediatric and adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. Idarubicin combined with Cytarabine and/or other antileukemic agents produced complete remissions in 46% of patients with refractory or relapsed AML and in 58% of patients with refractory or relapsed ALL (adult and pediatric). Subsequently, Idarubicin has been employed in untreated AML patients in combination with Cytarabine and/or Etoposide, producing complete remissions in more than 80% of patients. In ALL patients the drug has been used in combination with Vincristine, Cytarabine and Prednisone, producing complete remissions in 82% of patients. Recently, Idarubicin has been utilized in combination with intermediate doses of Cytarabine in refractory or relapsed ALL and AML, and 70% of patients achieved complete remission. Preliminary results of ongoing prospective randomized studies in untreated adult AML seem indicate that Idarubicin is at least equivalent, if not superior to Daunorubicin. The antileukemic activity of Idarubicin given orally as single agent, or in combination with other drugs, has been shown in AML and myelodysplastic syndromes. The toxicity of Idarubicin includes mild nausea and vomiting, alopecia and liver dysfunction. Ongoing randomized trials comparing Idarubicin to Daunorubicin should provide more information about the potential cardiotoxicity of this drug.
 ...
PMID:Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies. 219 43

Peripheral blood stem cells (PBSC) were collected from 24 patients who were treated with high dose etoposide. Studied patients included one with acute lymphoblastic leukemia, 4 with acute myeloid leukemia (AML), 1 with myelodysplastic syndrome, 13 with lymphoma, 1 with malignant histiocytosis, 2 with myeloma, and 4 with testicular tumor. Etoposide was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant human granulocyte-colony stimulating factor from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all patients, the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the patients (73%). All leukemia patients treated along with our protocols have remained in complete remission, but one patient with AML relapsed within 1 month after the treatment. Ten lymphoma patients were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one patient. Two patients with myeloma were classified to be NC. Three of the 4 patients with testicular tumor were PR, and the other one was NC. Eleven patients subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.
 ...
PMID:[Peripheral blood stem cell collection with high dose etoposide]. 754 Feb 21

The therapy for myelodysplastic syndromes (MDS) and acute leukemia (AL) transformed from MDS is not well established. Etoposide (VP 16-213) at low concentrations shows differentiation-inducing activity against leukemic cells in vitro. A prior study showed that oral low-dose etoposide therapy was effective in patients with chronic myelomonocytic leukemia. We used low-dose etoposide to treat six patients with refractory anemia with excess blasts in transformation (RAEB-t) and seven patients with AL transformed from MDS. The etoposide (50 mg, 2-7 times/week) was usually administered intravenously to ensure reliable bioavailability. Of 12 assessable patients, four RAEB-t patients achieved a partial response and one AL patient achieved complete remission. The responders became transfusion-independent, and this continued for 2-9 months while etoposide therapy was continued. Three of five responders had been resistant to prior repeated low-dose cytarabine therapy. The side effects were mild and well tolerated. Heterogeneous mechanisms were surmised to explain the clinical effects of low-dose etoposide. Several aspects, including the optimal schedule of low-dose etoposide therapy, the effect of this therapy on the patients' survival, the usefulness of combination therapy with other chemotherapeutic drug(s) and/or cytokine(s), should be investigated in the future.
 ...
PMID:Application of low-dose etoposide therapy for myelodysplastic syndromes. 816 35

80-year-old female was admitted to our hospital because of pancytopenia. Her peripheral and bone marrow examinations were performed. According to the criteria of FAB classification, the diagnosis was myelodysplastic syndrome (refractory anemia with excess of blasts in transformation). Etoposide was administered to decrease leukemic blasts. However, she still had high fever and increasing of CRP. Hematological data also showed the increasing of WBC count, blast cells, and LDH enzyme. Antibiotics and anti fungal drugs were also not effective. She died of respiratory failure, although the cautions and extensive treatment was tried. Autopsy findings revealed proliferation of mucor in the mucosa of stomach. So, we reported here a very rare case of gastric mucormycosis, localizing exclusively in the stomach which was difficult to diagnose while she was alive.
 ...
PMID:[Myelodysplastic syndrome developing acute myelocytic leukemia with gastric mucormycosis]. 825 69

Five cases of myelodysplastic syndrome were treated with cytarabine ocfosfate. Ocfosfate (100-200 mg) was orally administered for 14 days with 14 days' interval. Etoposide was combined in one case, and nartograstim was added in two cases. Two of the five cases achieved remission, one case having complete remission, and another case showing a good response. Their remission durations were 141 and 112 days, respectively. Further improvement of therapy is needed to achieve a higher remission rate and a longer remission duration.
 ...
PMID:[Five cases of myelodysplastic syndrome treated with cytarabine ocfosfate]. 883 48

We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.
 ...
PMID:Therapy-related leukemia and myelodysplasia following oral administration of etoposide for recurrent breast cancer. 962 8

P39/Tsugane is a myelomonocytoid cell line derived from a patient with myelodysplastic syndrome (MDS). The cells readily undergo apoptosis in response to various agents, and the cell line has been suggested as a useful model to study apoptosis in MDS. The aims of the present study were to assess differentiation and apoptosis induced with all-trans retinoic acid (ATRA) and etoposide, to characterize the mode of apoptosis in these two model systems, and to assess the influence of granulocyte colony-stimulating factor (G-CSF), which in combination with erythropoietin has been shown to inhibit apoptosis in MDS. ATRA induced differentiation and apoptosis in a concentration- and time-dependent manner. Differentiated cells were partially rescued (by 50%) from apoptosis with G-CSF. Etoposide induced apoptosis in a concentration- and time-dependent manner, but no signs of preceding maturation or G-CSF rescue were detected. ATRA- and etoposide-induced apoptosis were both mediated through the caspase pathway and were partially blocked with the general caspase inhibitor zVAD-fmk. Simultaneous treatment with G-CSF and zVAD-fmk additively blocked ATRA-induced apoptosis. However, the two pathways differed in terms of substrate cleavage during apoptosis. ATRA-induced apoptosis caused actin cleavage, which was not affected by G-CSF, and Bcl-2 downregulation. Etoposide induced a caspase-dependent cleavage of Bcl-2, while actin remained intact. The Fas system did not seem to play a major role in any of these apoptotic pathways. Our results may provide new tools to study the mechanisms of apoptosis in MDS.
 ...
PMID:Two pathways of apoptosis induced with all-trans retinoic acid and etoposide in the myeloid cell line P39. 1042 9

Testicular cancer is the most common solid tumour among young males aged 15-35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud's phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud's phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud's phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2-5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.
 ...
PMID:Long-term complications of chemotherapy for germ cell tumours. 1288 63

We report a patient with a refractory testicular non-seminomatous germ cell tumor (NSGCT) who developed therapy-related leukemia (TRL) after undergoing salvage chemotherapy and multiple operations for repeat recurrences. Fifty months after the initial therapy, pancytopenia and myeloblasts were observed in the patient's peripheral blood while the patient was undergoing salvage chemotherapy for a fifth recurrence. A bone marrow examination showed evidence of myelodysplastic syndrome (MDS) and refractory anemia with excess of blasts in transformation (RAEB in T) under French-America-British (FAB) classification. Cytogenetic 5q-/7q- abnormalities were also observed. The patient had received a total dose of 189g/m2 of Ifosfamide, 8,250mg/m2 of Etoposide and 1,450 mg/m2 of Cisplatin; therefore, he was diagnosed as having TRL/MDS. The patient has received induction chemotherapy for TRL with Cytarabine, Daunorubicin and Fludarabine while a bone marrow transplantation has been scheduled. Recently, TRL associated with chemotherapy are being reported with increasing frequency in the literature. Since early detection and treatment are necessary for the management of TRL, peripheral blood examinations should be performed after a diagnosis of refractory germ cell tumor has been made. If pancytopenia is detected, bone marrow and cytogenetic examinations should be immediately performed to rule out TRL.
 ...
PMID:[A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor]. 1636 57

We prospectively observed a child exposed to intensive multimodality therapy for metastatic neuroblastoma from emergence of a MLL translocation to disease diagnosis. The t(4;11)(p12;q23) was detected in the marrow 17 months after starting treatment following topoisomerase II poisons, alkylating agents, local radiation, hematopoietic stem cell transplantation, anti-GD2 monoclonal antibody with granulocyte macrophage-colony-stimulating factor, and a high cumulative dose of oral etoposide. Reciprocal genomic breakpoint junctions and fusion transcripts joined MLL with FRYL, the Drosophila melanogaster protein homologue of which regulates cell fate. Etoposide metabolites induced topoisomerase II cleavage complexes that could form both breakpoint junctions. Cells harboring the translocation replaced the marrow without clinical evidence of leukemia and differentiation appeared unaffected for 37 months. Subsequent bilineage dysplasia and increased blasts in addition to the translocation fulfilled criteria for MDS. The MEIS1 target gene of typical MLL fusion oncoproteins was underexpressed before and at MDS diagnosis. These results are consistent with repair of topoisomerase II cleavage from etoposide metabolites as the translocation mechanism, whereas other agents in the regimen may have contributed to progression of the clone with the translocation to MDS. MLL-FRYL did not increase MEIS1 expression, conferred a proliferative advantage without altering differentiation, and had protracted latency to disease.
 ...
PMID:Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome. 1819 96


1 2 Next >>