Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MOPP (mechlorethamine, vincristine, procarbazine, prednisone) was the first successful regimen for the treatment of Hodgkin's disease. It has the longest period of follow-up and is best studied as to its benefits and acute and long-term side effects. The acute toxicity of the side effects, including nausea and/or vomiting, hair loss, and myelosuppression, may have been reason to modify doses of nitrogen mustard, an agent whose dose intensity may be critical in achieving long-term benefits. The substitution of chlorambucil and vinblastine in the ChlVPP (chlorambucil, vinblastine, procarbazine, prednisone) program has relieved all of these acute toxicities, except myelosuppression. The long-term toxicity of sterility, especially in males, and myelodysplasia is most likely due to alkylating-agent toxicity and would not be influenced by the various MOPP variants, such as MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), ChlVPP, and COPP (chlorambucil-vincristine, procarbazine, prednisone). Doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and ABDIC (doxorubicin, bleomycin, dacarbazine, lomustine, prednisone), have been second-line treatments that have significant antitumor effect and, as such, have resulted in few, if any, long-term cures in most series. ABVD has been incorporated into alternating MOPP/ABVD schemes or in hybrids that attempt to offer all active agents, such as MOPP/ABV. The initial experience has been encouraging with high and durable complete remissions (CRs). MOPP/ABVD x 12(1) and MOPP-2/ABVD-2(2) have been compared with MOPP alone with a significant superiority for the alternating regimens. Other randomized trials have not shown any superiority for the alternating program. The Cancer and Leukemia Group B (CALGB) has compared MOPP with MOPP/ABVD given with a third arm of ABVD alone. The complete response and time-to-treatment failure rates for MOPP/ABVD and ABVD alone were superior to those for MOPP. Significant modifications of MOPP doses may explain the differences, since only 20% of patients were receiving full doses of nitrogen mustard by the sixth dose. ABVD has unique toxicity, and myelodysplasia and sterility are not seen. Pulmonary fibrosis with radiation and bleomycin is unique to ABVD, as shown in the ABVD experience at the NCl (Milan). Can ABVD be improved? The demonstrated single-dose activity of etoposide in Hodgkin's disease has prompted its inclusion in second-line programs, such as EVA (etoposide, vincristine or vinblastine, doxorubicin). The second-line response rates in the St Bartholomew's (London, England) series (where vincristine was used) was 11 of 19 patients (58%);3 in the ongoing CALGB trial of EVA (vinblastine combination), the response rate is 67%. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Can MOPP be replaced in the treatment of advanced Hodgkin's disease? 168 9

The introduction of modern methods of combined therapy: chemotherapy and radiotherapy, allows the cure more than 90% of children and adolescents with Hodgkin's disease. However, the intensive treatment may cause early and late complications. The late complications may include: damage of soft tissues and respiratory, cardiovascular, skeletal, and endocrine systems, and second cancers. Late complications may impair the patients' quality of life after cessation of therapy. This study presents evaluation of health status of persons who underwent therapy for pediatric Hodgkin's disease in centers of Polish Pediatric Leukemia/Lymphoma Study Group. The special questionnaire was established to collect data concerning hematopoietic system function, damage of soft tissues and skeletal system, thyroid and reproductive organs function, respiratory, cardiovascular, and nervous system function, liver and kidney function, status of dentition, occurrence of infections, immunologic system function, and psychological and social problems. The project included patients treated in 9 pediatric oncology centers. During the study the questionnaires of 288 patients [151 boys (52.4%) and 137 girls (47.6%)] in whom treatment of Hodgkins's disease started in 1994-1996 (44 questionnaires), and in 1997-2001 (244 questionnaires). In 42 patients no diagnostic procedures were performed. In this group 20 patients are currently under care of adult oncology clinics, 21 failed to come for a visit, and one patient is treated because of HD progression. The questionnaires of 246 patients treated in 1994-1996 (25 questionnaires) and 1997-2001 (221 questionnaires), were analyzed and the data on the late complications of these patients were obtained. General health status of examined patients was found satisfactory. However, 2.3% of patients had radiological evidence of pulmonary fibrosis, and 4.9% had various ECG abnormalities. Endocrine therapy is needed in 4.5% of patients because of thyroid function abnormalities. Second cancers were diagnosed in 1.7% of patients. The health status of children and adolescents cured from Hodgkin's disease and other childhood cancers should be regularly evaluated. Results of these evaluations will be the basis for introducing new treatment protocols aimed of decreasing the incidence of late complications while maintaining or improving cure rates.
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PMID:[The health state evaluation in persons after therapy of Hodgkin's disease in childhood: report of the Polish Pediatric Leukemia/Lymphoma Study Group]. 1689 95

The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.
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PMID:Pediatric leukemia susceptibility disorders: manifestations and management. 2922 62