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)

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goitre. One to three doses of 300-550 MBq of 131I were administered at 1-week intervals. Lymphocyte counts were found to be significantly reduced at both 1 and 6 weeks after treatment. This decrease was accompanied by a changed composition of the lymphocyte subpopulations. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming cells) was significantly reduced at 1 and 6 weeks following 131I administration. At 6 weeks there was a small but statistically significant increase of the frequency of T cells as identified by Leu 1 monoclonal antibodies. This was essentially due to an increased proportion of helper/inducer T cells as identified by Leu 3 monoclonals. 131I treatment also decreased the capacity of lymphocytes to secrete immunoglobulins (Ig) when stimulated with pokeweed mitogen (PWM). The greatest effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with phytohemagglutinin (PHA) and concanavalin A were not significantly changed. It is concluded that these findings, with the exception of mitogen reactivity, are largely similar to those occurring following external radiation therapy for cancer. It is suggested that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by beta-rays. The effect of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythemia vera. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as identified by monoclonal antibodies against total T cells (Leu 1 and 4), helper/inducer (Leu 3) and suppressor/cytotoxic T cells (Leu 2), were slightly decreased. Moreover, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were impaired. Following a single oral dose of 32P (150-305 MBq), which normalized the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40 per cent 12 weeks after treatment. Examination of subsets demonstrated that the proportion of B-cells, as identified by B1 monoclonal antibodies, was decreased by the highest relative extent. On the other hand, lymphocytes expressing the above-mentioned T cell markers were somewhat increased. 32P treatment markedly increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in agreement with the finding that serum concentrations of Ig were reduced after treatment.
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PMID:Changes of the blood lymphocyte subpopulations and their functions following 131I treatment for nodular goitre and 32P treatment for polycythemia vera. 325 74

The analysis of 288 cases of polycythemia vera (PV) with a minimal follow-up of 10 years enabled us to study the characteristics of acute leukemia as observed in 33 patients (11.4%). In 50% of the patients (16 of 33), the malignant transformation is of the refractory anemia with excess of blasts (RAEB) type. Half of these further transform to acute nonlymphocytic leukemia (ANLL). Their life expectancy is not better than patients who abruptly develop ANLL. Leukemic transformation shows a frequency peak in the eighth year after initial evaluation in PV treated with chemotherapy and in the 11th year in patients treated with radiotherapy. In 30% of the patients myelofibrosis, or the spent phase of PV, is present before the transformation to acute leukemia (AL). This complication is, however, part of the natural history of PV and is observed in 20% of PV patients at 10 years when leukemic transformation is absent. Marrow fibrosis can therefore not be considered as a preleukemic phase. It was also noted that the occurrence of myeloid metaplasia/myelofibrosis is more frequent and begins earlier in patients treated by phlebotomy alone, and who do not transform to leukemia. The clinical characteristics of these AL, including high frequency of partial marrow invasion, difficulties in cytologic classification, a peak incidence similar to that in patients treated by chemotherapy or radiotherapy for a prior malignancy, multiple chromosome abnormalities, and poor response to therapy are all highly suggestive of secondary leukemias.
Cancer 1988 Jan 01
PMID:Acute leukemia and myelodysplasia in polycythemia vera. A clinical study with long-term follow-up. 333 54

The case of a patient with a history of polycythemia vera and 46,XX karyotype who transformed into acute nonlymphocytic leukemia with 46,XX,t(1;3)(p36;q21) rearrangement is reported. Significant percentages of the circulating blasts in the peripheral blood were positive on immunocytochemical stains for megakaryocyte markers, anti-Factor VIII, and antiglycoprotein IIb/IIIa. On the basis of our studies and published reports, trilineage hematopoietic abnormalities and a poor response to therapy may represent typical features of patients with t(1;3).
Cancer Genet Cytogenet 1988 Jul 15
PMID:Transformation of polycythemia vera to acute nonlymphocytic leukemia accompanied by t(1;3)(p36;q21) karyotype. 338 67

In recent years, radiolabelled monoclonal antibodies have been evaluated for their use in the diagnosis and treatment of neoplastic disease. One isotope which has not been assessed for antibody targeting is 32P, even though it has many favourable radiobiological characteristics and has been used clinically for the treatment of certain neoplastic disorders such as polycythaemia rubra vera. The main drawback so far in using 32P has been the absence of a general method for phosphorylating antibodies. We have now developed a novel process for the phosphorylation of immunoglobulins which is rapid, efficient and allows high specific activities to be achieved (greater than 10 muCi micrograms-1). The technique involves the chemical conjugation of Kemptide, a synthetic heptapeptide substrate for kinases, to immunoglobulins. The antibody-Kemptide conjugate can then be phosphorylated using protein kinases and [32P]-gamma-ATP. The procedure does not compromise the binding activity of the antibody. The 32P-labelled monoclonal antibodies were stable in human, mouse and rat plasmas in vitro, although they cleared from the bloodstream of mice with a beta-phase half life of 2 days which is approximately two times faster than that of native antibody. The application of this phosphorylation technique should allow the therapeutic potential of targeted 32P to be assessed.
Br J Cancer 1988 May
PMID:Conjugation of monoclonal antibodies to a synthetic peptide substrate for protein kinase: a method for labelling antibodies with 32P. 339 53

The antigenic phenotype of myelomonocytic progenitors [colony-forming unit granulocyte-macrophage (CFU-GM)] from 33 patients with chronic myeloproliferative disorders was investigated using four cytotoxic monoclonal antibodies. Monoclonal antibodies S3-13, S8-6, and S16-144 which recognize normal hemopoietic progenitors of different lineages reacted with almost all CFU-GM. R1B-19 monoclonal antibody identified two subpopulations of myelomonocytic progenitors (type 1 and 2 CFU-GM), as reported previously in normal subjects. In 3 of 11 patients with chronic myelogenous leukemia, in 1 of 2 patients with chronic myelomonocytic leukemia, and in 2 of 4 patients with polycythemia vera, a higher proportion of the more immature CFU-GM (type 1) was detected in bone marrow cells. The more differentiated CFU-GM (type 2) is not detectable in normal peripheral blood. By contrast, in 14 of 15 chronic myelogenous leukemia patients, in 1 of 2 chronic myelomonocytic leukemia patients and in 3 of 8 patients with idiopathic myelofibrosis, it was present in high to very high proportions. It is clear from these findings that the antigens present on normal CFU-GM are expressed in chronic myeloproliferative disorders. The proportion and distribution of type 1 and 2 CFU-GM, on the other hand, are very different from those observed in the normal subjects.
Cancer Res 1986 Feb
PMID:Antigenic phenotype of myelomonocytic progenitors (CFU-GM) in chronic myeloproliferative disorders. 345 79

The incidence of characteristic nonrandom chromosome aberrations in malignant cells of unselected, consecutively studied, and previously untreated patients from various geographic regions has been surveyed. The results demonstrate significant geographic heterogeneity in the distribution of the specific aberrations considered among the four malignant disorders studied in a sufficient number to permit conclusions, viz., acute nonlymphocytic leukemia, chronic myeloid leukemia, polycythemia vera, and myelodysplastic syndrome.
Cancer Genet Cytogenet 1986 Feb 15
PMID:Geographic heterogeneity of chromosome aberrations in hematologic disorders. 345 65

A 52-year-old man with polycythemia vera of 20 years duration with progression to myelofibrosis developed a mass arising from the sternum. The mass consisted of large poorly differentiated cells infiltrating skeletal muscle, with cytochemical and ultrastructural features of malignant histiocytosis. At autopsy 6 weeks later, his bone marrow and spleen were involved by acute myelogenous leukemia. This is the first reported case of malignant histiocytosis occurring in a patient with polycythemia vera, and the second report of its association with acute myelogenous leukemia. There is suggestive evidence in this case that the malignant histiocytosis may possibly have arisen from the polycythemia vera clone.
Cancer 1987 Feb 01
PMID:Malignant histiocytosis occurring with acute myelogenous leukemia in a patient with longstanding polycythemia vera. 346 64

Eight patients with myeloproliferative disorders, five with polycythaemia rubra vera (PRV) and three with essential thrombocythaemia (ET), have been treated with the anti-folate drug Pyrimethamine for periods ranging from 1 to 24 years. In PRV this treatment was comparable in efficacy to that achieved with Busulphan or radioactive phosphorus, but required more frequent supervision. One patient was controlled on Pyrimethamine, having failed on conventional treatment. The major side effect was thrombocytopenia which was rapidly reversible on stopping the drug. In ET, Pyrimethamine produced satisfactory control of the platelet count and thrombocytopenia did not arise. No neurological sequelae were encountered. One patient developed a non-Hodgkin's lymphoma of the gut, but there were no other cases of secondary malignancy. Pyrimethamine may still have a role in the treatment of selected cases of myeloproliferative disorders.
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PMID:Pyrimethamine in the myeloproliferative disorders: a forgotten treatment? 362 57

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.
Cancer Immunol Immunother 1987
PMID:Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders. 367 27

The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.
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PMID:Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. 370 65


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