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)

This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Stanford experience with combined procarbazine, Alkeran and vinblastine (PAVe) and radiotherapy for locally extensive and advanced stage Hodgkin's disease. 145 64

The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.
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PMID:Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients. 1457 60

Hodgkin's disease has been treated mainly with two chemotherapy schedules, MOPP (nitrogen mustard, Oncovin, procarbazine and prednisone), which includes alkylating agents, and ABVD (adriamycin, bleomycin, vinblastine and dacarbazine), which includes topoisomerase II inhibitors, either with or without radiation therapy. Due to the types of agents used, patients with Hodgkin's disease often develop secondary leukemias. The alkylating agents included in the MOPP scheme were the first drugs associated with the development of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML); both entities are the result of the clonal selection of cells with accumulated genomic lesions induced by antineoplastic therapy. In patients who developed t-MDS and t-AML, eight alternative routes with specific cytogenetic and molecular changes have been identified, and the routes are related to the type of therapy, alkylating agents or DNA topoisomerase II inhibitors. At the cytogenetic level, patients treated with alkylating agents show deletion 5q/monosomy 5 and deletion 7q/monosomy 7; in contrast, those who were treated with topoisomerase II inhibitors show 11q23 translocations involving the MLL gene. At the molecular level, there are two types of mutations: Class I, which alter the RAS-BRAF signal transduction pathways and increase cell proliferation; Class II, which disrupt genes that encode transcription factors and NPM1 that are involved in cell differentiation, and the inactivation of p53 tumor suppressor gene. Knowledge of the genetic alterations in these conditions is important for the classification, treatment and prognosis of patients as well as essential for increasing the knowledge of the biology of these diseases, which leads to identifying potential therapeutic targets.
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PMID:Genetic abnormalities in leukemia secondary to treatment in patients with Hodgkin's disease. 2157 43