Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with myelofibrosis with myeloid metaplasia (MMM), with or without preceding polycythemia vera or essential thrombocythemia, with a primary aim to improve anemia. Thalidomide was given in escalating doses with a target dose of 800 mg daily, but the median dose of thalidomide that was actually tolerated was 400 mg daily. Fifteen patients were entered into the study and 14 were evaluable for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo because of side effects, and none of these five patients had a response at the time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of the remaining nine patients exhibited a discernible clinical response. Three patients showed progressive disease defined as > 50% increase in the need for red cell transfusions. Treatment was poorly tolerated, with all patients reporting side effects of thalidomide, the most prominent being fatigue documented in 80% of patients. Two patients died while on study, one from acute myelogenous leukemia and one from pneumonia. We conclude that thalidomide given in doses employed in the treatment of multiple myeloma gives no clinically relevant hematological effects in advanced MMM and is hampered by a very high incidence of side effects.
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PMID:Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia. 1218 Apr 84

Myelofibrosis with myeloid metaplasia (MMM) encompasses the diagnoses of agnogenic myeloid metaplasia (idiopathic myelofibrosis), as well as the advanced phases of polycythemia vera and essential thrombocythemia (post polycythemic and post thrombocythemia myeloid metaplasia, respectively). MMM is a clonal, hematopoietic stem cell disorder in which neither the pathogenesis, nor a broadly applicable effective therapy have been described. Clinically, these patients experience progressive marrow replacement by fibrotic tissue, ineffective hematopoiesis, problematic cytopenia's, significant hepato-splenomegaly, extramedullary hematopoiesis, profound constitutional symptoms, and a risk of blastic transformation. Historically, therapies have been targeted at palliating symptoms (i.e. splenectomy, transfusions, hydroxyurea, erythropoietin, androgens, localized radiotherapy). Stem cell transplantation appears promising, but is often toxic and not broadly applicable due to co-morbidities and age of MMM patients. Non-myeloablative approaches to conditioning may broaden the applicability of stem cell transplantation in MMM, yet results to date are preliminary. Although a definitive molecular abnormality responsible for the pathogenesis of MMM has not been described, much has been learned about the aberrant expression of pro-fibrotic cytokines and the presence of increased angiogenesis in MMM. These pathogenetic insights have led to a series of pilot clinical trials with therapeutic agents targeting aberrantly expressed cytokines (and possibly angiogenesis) including Thalidomide (alone or in combination), Etanercept, and STI-571. Amongst these later agents Thalidomide has demonstrated the most promise (palliating disease associated cytopenia's), whereas the TNF-alpha inhibitor Etanercept has aided with MMM associated constitutional symptoms. Although these later trials have been helpful in a subset of patients, no agent to date has led to solid complete responses in MMM across the spectrum of disease manifestations. Further insights into the pathogenetic mechanisms responsible for myeloproliferation (aberrant cell signaling pathways, apoptotic resistance, other) are necessary to guide selection and testing of the expanding number of novel anti-neoplastic agents in chronic myeloid disorders and MMM.
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PMID:The therapy of myelofibrosis: targeting pathogenesis. 1243 Sep 41