phosphorus-radioisotopes and Polycythemia-Vera

Polycythemia vera, essential thrombocythemia, and primary myleofibrosis are chronic myeloproliferative neoplasms (MPNs) associated with an increased morbidity and mortality. MPNs are also associated with progression to acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The "true" rate of transformation is not known mainly due to selection bias in clinical trials and underreporting in population-based studies. The outcome after transformation is dismal. The underlying mechanisms of transformation are incompletely understood and in part remain an area of controversy. There is an intrinsic propensity in MPNs to progress to AML/MDS, the magnitude of which is not fully known, supporting a role for nontreatment-related factors. High doses of alkylating agents, P(32) and combined cytoreductive treatments undoubtedly increase the risk of transformation. The potential leukemogenic role of hydroxyurea has been a matter of debate due to difficulties in performing large prospective randomized trials addressing this issue. The main focus of this review is to elucidate therapy-related leukemic transformation in MPNs with a special focus on the role of hydroxyurea.

Topics: Antineoplastic Agents; Cell Transformation, Neoplastic; Disease Progression; Humans; Hydroxyurea; Janus Kinase 2; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Survival Analysis; Thrombocythemia, Essential

Hydroxyurea is an old drug that is often used to control essential thrombocythemia and polycythemia vera in patients with high-risk disease. It is usually well tolerated and cheap and has been proven effective in many studies for the prevention of thrombohemorrhagic complications associated with these disorders. However, many clinicians are reluctant to use it because of the perceived risk of progression to acute leukemia. Several recent, large studies have given this drug a new lease on life. Relevant results from these studies are discussed, and the risk of leukemia is placed in perspective to demonstrate that hydroxyurea remains the drug of choice in patients with either of these disorders.

Topics: Aged; Agranulocytosis; Alkylating Agents; Clinical Trials as Topic; Combined Modality Therapy; Disease Progression; Evidence-Based Medicine; Hemorrhage; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocythemia, Essential; Thrombophilia

Since 1903 when polycythemia vera was designated by Osler as a new identity the clinical manifestations at the time of diagnosis--symptomatology, physical and hematological findings have become well known. Criteria for diagnosis have been established as well as treatment goals. However, agreement on how best to treat this disease has eluded the hematologists particularly as our understanding of the evolution of the hematological findings has become better known. The hemorrhagic and thrombotic complications and acute leukemia in patients managed with myelosuppressive regimens have come to the forefront. Criteria to be used in the comparison of treatment regimens are suggested from which in this author's opinion the use of 32P becomes the treatment of choice, but not all will agree.

Topics: Antineoplastic Agents; Hemorrhagic Disorders; Humans; Leukemia; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Remission Induction; Thrombosis

Topics: Anemia; Apoptosis; Clone Cells; Disease Progression; Erythropoiesis; Erythropoietin; Female; Growth Substances; Hematologic Tests; Hematopoietic Stem Cells; Humans; Iron; Leukemia, Myeloid; Male; Myeloproliferative Disorders; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Erythropoietin; Receptors, Growth Factor; Thrombocytosis; Thrombosis

Several options exist for treating essential thrombocythemia and polycythemia vera. One approach is to assign the patient to a risk category from which treatment recommendations follow. The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis. Risk factors for thrombosis include age and prior thrombosis. Smoking and obesity have been implicated in isolated series. High-risk patients with essential thrombocythemia can be defined as those 60 years of age or older or those who have had a thrombosis at any age. These patients should be treated with hydroxyurea. If hydroxyurea cannot be tolerated, anagrelide and interferon-alpha (IFN-alpha) are alternatives. Low-dose aspirin (40 to 325 mg) can be used for patients whose platelet counts are < 1,500 x10(9)/L. Low-risk patients are those less than 60 years old who have not had thrombosis, who have no cardiovascular risk factors, and whose platelet counts are < 1,500 x 10(9)/L. These patients can be observed or placed on low-dose aspirin. Intermediate-risk patients are those less than 60 years who have not had thromboses, but who have platelet counts > 1,500 x 10(9)/L or who have significant cardiovascular risk factors. These patients should have their risk factors treated and may be given low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. They can be observed or treated with anagrelide, hydroxyurea, or IFN-alpha. The Mayo Clinic experience suggests that no specific treatment affects outcomes of pregnancies. In high-risk pregnant women who need treatment, IFN-alpha is used. The principal risks of polycythemia vera are thrombosis, postpolycythemia myeloid metaplasia, and acute leukemia. Risk factors for thrombosis include age, the use of phlebotomies, the rate of phlebotomies, and a prior history of thrombosis. Platelet counts have not been definitively linked to an increased risk of thrombosis. High-risk polycythemia vera patients are those 60 years of age or older (some groups use 70 years) or those of any age who have had thrombosis. They should be treated with phlebotomy and hydroxyurea or IFN-alpha. Selected patients may be treated with anagrelide. A typical target range for phlebotomy is a hematocrit of < 42% for women and < 45% for men. Low-dose aspirin can be used if the platelet count is < 1,500 x 10(9)/L. Low-risk patients are those less than 60 years old who have had no thrombosis, no cardiovascular risk factors, and whos

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Aspirin; Busulfan; Fibrinolytic Agents; Humans; Hydroxyurea; Immunologic Factors; Immunosuppressive Agents; Interferon-alpha; Nucleic Acid Synthesis Inhibitors; Phosphorus Radioisotopes; Polycythemia Vera; Quinazolines; Risk Assessment; Thrombocytosis

By definition, idiopathic erythrocytosis (IE) applies to a group of patients characterised by having a measured RCM above their predicted normal range (an absolute erythrocytosis) and following investigation do not have a form of primary or secondary erythrocytosis. Patients with IE are heterogenous. The possibilities include physiological variation, 'early' polycythaemia vera (10-15% develop clear features of PV over a few years), unrecognized congenital erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis or a currently undescribed form of primary or secondary erythrocytosis. Patients are more commonly male with a median age at presentation of 55-60 years. Approximately half of the patients present with vascular occlusive complications. Retrospective evidence indicates that vascular occlusion occurs less frequently when the PCV is controlled at normal levels. Venesection is the treatment of choice to lower the PCV. As a general approach to management, all patients with a PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV should also apply to patients with lesser degrees of raised PCV who have additional other risk factors for vascular occlusion.

Topics: Aged; Arterial Occlusive Diseases; Bone Marrow; Chlorambucil; Diagnosis, Differential; Endocrine System Diseases; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Genetic Predisposition to Disease; Humans; Hypoxia; Kidney Diseases; Leukemia; Leukemia, Radiation-Induced; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Receptors, Erythropoietin; Sequence Deletion; Smoking; Stroke

The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory animals that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. After World War II when 32P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best?

Topics: Adult; Aged; Alkylating Agents; Chlorambucil; Clinical Trials as Topic; Combined Modality Therapy; Drug Utilization; Humans; Hydroxyurea; Immunologic Factors; Interferons; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Myeloproliferative Disorders; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Thrombocythemia, Essential

Topics: Aged; Antineoplastic Agents, Alkylating; Antisickling Agents; Diagnosis, Differential; Female; Humans; Hydroxyurea; Injections, Intravenous; Interferon-alpha; Male; Middle Aged; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Risk Factors; Sex Factors

The clinical course in both polycythaemia vera (PV) and essential thrombocythaemia (ET) is characterized by significant thrombohaemorrhagic complications and variable risk of disease transformation into myeloid metaplasia with myelofibrosis or acute myeloid leukaemia. Randomized studies have shown that the risk of thrombosis was significantly reduced in ET with the use of hydroxyurea (HU) and in PV with the use of chlorambucil or 32P. However, the use of chlorambucil or 32P has been associated with an increased risk of leukaemic transformation. Subsequently, other studies have suggested that both HU and pipobroman may be less leukaemogenic and as effective as chlorambucil and 32P for preventing thrombosis in PV. However, the results from these prospective studies have raised concern that even HU and pipobroman may be associated with excess leukaemic events in both ET and PV. The recent introduction of anagrelide as a specific platelet-lowering agent, the demonstration of treatment efficacy with interferon-alpha, and the revived interest in using low-dose acetylsalicylic acid provide the opportunity to initiate prospective randomized studies incorporating these treatments.

Topics: Adult; Aged; Aspirin; Chlorambucil; Disease Progression; Female; Hemorrhage; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prospective Studies; Quinazolines; Thrombocythemia, Essential; Thrombosis

Following the development of the cyclotron in 1932, radio-isotopes became available for use in medicine both as tracer substances and therapeutic agents. The father of nuclear medicine, Dr J. H. Lawrence, pioneered their use in a range of disease states and found that radio-isotopes were of enormous value in the diagnosis and treatment of haemopoetic disease, particularly the myeloproliferative disorders. Radioactive phosphorus 32P emerged as the radio-isotope of choice for the myelosuppressive treatment of myeloproliferative disorders. This article also describes the use of radio-isotopes in the treatment of other disorders: chronic myeloid leukaemia, chronic lymphocytic leukaemia and myeloma, work that is now largely forgotten. All myeloproliferative disorders may evolve without treatment into myelodysplastic syndrome or blast-cell transformation. It is accepted that life is prolonged in myeloproliferative disorders treated with 32P or alkylating agents, yet both are leukaemogenic. The ideal form of treatment for polycythaemia vera is unknown and will remain so, for patients with this disorder often outlive their physician and achieve 90% of normal life expectation. 32P remains the treatment of choice for elderly patients with polycythaemia vera.

Topics: Animals; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Acute Disease; Alkylating Agents; Busulfan; Chlorambucil; Humans; Hydroxyurea; Leukemia, Myeloid; Leukemia, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Survival Rate

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

The treatment of polycythemia vera with 32phosphorus (32P) raises two problems: 1) what is its therapeutic efficacity? 2) Does the use of 32P increase the risk of acute leukemia? The large series of treated patients have shown the remarkable efficacy of 32P. This is particularly evident when comparing the recent series of patients treated with 32P with those of Videbaek whose patients were treated by phlebotomies only. Patients are treated one time with 3.7 x 10(6) mBq (0.1 mCi) of 33P per kg of body weight. Granulocytes and platelets are rapidly affected, whereas red cells show a response 3 months later due to their longer survival. Remission lasts from a few months to three years. If the result is not satisfactory, another dose can be given 3 months after the first one. Resistance to 32P may arise but may be reversible after a course of chemotherapy. The clear therapeutic effect of 32P renders it especially valuable for patients with a high vascular risk. Some authors have claimed that polycythemia vera evolves towards acute leukemia, but Modan's study has demonstrated that 32P is indeed responsible for the occurrence of acute leukemia; this has been largely confirmed by others. The dose to the bone marrow is not negligible and the leukemic incidence following the treatment is a factor which limits its indication. Trials were conducted to search for therapies with alkylating agents, such as Chlorambucil or Busulphan, which would be less leukemogenic. The Polycythemia Vera Study Group found that Chlorambucil was at least 2.3 fold more leukemogenic than 32P. The EORTC compared the leukemogenic effect of 32P with that of Busulphan.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Cell Division; Humans; Leukemia, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera; Risk Factors

We present a patient diagnosed of polycythemia vera who developed a multiple myeloma 13 years after the initial diagnosis of polycythemia vera. Although an unusual finding, another 17 patients with polycythemia and myeloma have been described. In some patients the diagnosis of both diseases was simultaneous but in most cases myeloma developed years after polycythemia vera. Some patients received only venipuncture for treatment of polycythemia vera so the appearance of multiple myeloma could not be explained on the grounds of chemotherapy induced second neoplasm. An explanation for this association is suggested.

Topics: Aged; Bloodletting; Busulfan; Combined Modality Therapy; Humans; Male; Multiple Myeloma; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Adult; Antineoplastic Agents; Busulfan; Follow-Up Studies; Hemorrhage; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Leukemia; Middle Aged; Phosphorus Radioisotopes; Plateletpheresis; Polycythemia Vera; Risk Factors; Thrombocythemia, Essential; Thrombosis

The diagnostic and therapeutic application of radionuclides in oncology has led to an increased efficiency in the treatment of malignant tumors. Regarding diagnosis, measuring metabolic reactions in tumor tissue, especially by positron emission tomography, opened the potential for assaying tumor response to different treatment modalities and thus eventually for tailoring effective treatment of a given tumor in the individual patient. Regarding treatment, attention is given to the choice of the radionuclide for optimal deposition of the desired radiation in tumor cells avoiding exposure of normal cells; in this context microdosimetric considerations are essential with respect to beta-emitters, alpha-emitters, the Auger-effect and neutron capture therapy. Examples of therapeutic uses of radionuclides in the inorganic form are 131-I for thyroid cancer and 32-P for polycythemia vera; organically bound radionuclides are employed with precursors for tumor cell metabolism or with receptor seeking agents, such as MIBG and monoclonal antibodies which presently enjoy a particular interest and bear great promise. Stable nuclides, if properly accumulated within tumors, may be activated for therapy in situ, for example by thermal neutrons, as in neutron capture therapy using the 10-B (n, alpha)7-Li reaction. Treatment planning and execution with radionuclides have gained momentum over the past decade, yet much more needs to be done.

Topics: Antibodies, Monoclonal; Humans; Immunotherapy; Iodine Radioisotopes; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes; Radiotherapy Dosage; Thyroid Neoplasms; Tomography, Emission-Computed

Polycythemia vera, a clonal stem cell disorder, produces neurologic problems in 50-80% of patients. Some symptoms, such as headache and dizziness, are related to hyperviscosity, and respond immediately to reduction of cell counts. Others seem to result from an associated coagulopathy. Patients with polycythemia tend to develop both arterial and venous thrombosis and are prone to hemorrhages. Treatments for polycythemia include phlebotomy, chlorambucil supplemented with phlebotomy, and 32P plus phlebotomy. Whatever treatment is chosen, the aim of therapy should be to reduce the hematocrit to approximately 40-45%.

Topics: Bloodletting; Chlorambucil; Clinical Protocols; Combined Modality Therapy; Humans; Nervous System Diseases; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Acute Disease; Adult; Antineoplastic Agents; Bloodletting; Cell Transformation, Neoplastic; Chlorambucil; Female; Humans; Leukemia; Male; Phosphorus Radioisotopes; Polycythemia Vera; Pregnancy; Preleukemia; Prognosis; Pruritus; Uric Acid

Topics: Alkylating Agents; Androgens; Blood; Bloodletting; Carbon Dioxide; Cobalt; Erythropoiesis; Erythropoietin; Humans; Hydrogen-Ion Concentration; Oxygen; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Virtually every aspect concerning the occurrence of acute leukemia in polycythemia vera is controversial. However, a list of those factors believed to have importance in leukemogenesis in this disease includes: maleness, ethnic origin, the presence of myeloid metaplasia and/or early WBC precursors in the peripheral blood at the time of presentation, the influence of prolonged survival, and a possible dose-response relationship with 32P treatment. Many of the features of PV suggest that it is a malignant disease per se, with other factors (such as clones of cells, or altered host response) combining to increase the leukemogenic potential of the agents used to control the disease. It does appear that the incidence of AL in PV treated with 32P and/or x-ray is many times higher than that for PV treated with phlebotomy alone. However, overall survival for 32P-treated patients appears to be longer than that for phlebotomy treatment. Further, for both 32P and phlebotomy treatments, patients with AL do not die an an earlier age than do patients not developing this complication. Since the transformation of PV into AL has been described in more than 20 patients treated with phlebotomy alone, and in more than 30 patients treated with chemotherapy and phlebotomy, the question concerning the occurrence of AL in PV no longer appears to revolve around whether this is a function of the leukemogenicity of 32P or the effect of prolongation of survival. The occurrence of AL in multiple myeloma, lymphomas, other malignancies, and in nonmalignant diseases following treatment with myelosuppressive agents, forces one to consider the leukemogenic potential of any agent capable of suppressing the panmyelopathy of this disease, as well as the inherent tendency to AL of the "untreated" disease. Hopefully, the next decade will give us a more complete understanding of the complex interrelationships between PV, its treatment, and AL.

Topics: Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Sex Factors

Topics: Anemia; Anemia, Sideroblastic; Animals; Chromosome Aberrations; Chromosome Disorders; Female; Granulocytes; Hematologic Diseases; Humans; Japan; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Male; Mice; Middle Aged; Nuclear Warfare; Phosphorus Radioisotopes; Polycythemia Vera; Precancerous Conditions; Radiation Injuries; Thrombocytopenia

Topics: Bone Marrow; Busulfan; Diagnosis, Differential; Erythropoiesis; Granulocytes; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Osteosclerosis; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Acute Disease; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 19-20; Chromosomes, Human, 21-22 and Y; Humans; Leukemia; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis

Topics: Bloodletting; Busulfan; Chlorambucil; Cyclophosphamide; Humans; Injections, Intravenous; International Cooperation; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Allopurinol; Bloodletting; Chlorambucil; Erythropoiesis; Gout; Humans; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera; Uric Acid

Topics: Anemia, Aplastic; Animals; Bacteriological Techniques; Bone Marrow; Glomerular Filtration Rate; Histological Techniques; Humans; Hypersplenism; Immunologic Techniques; Iodine Radioisotopes; Kidney; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Phosphorus Radioisotopes; Polycythemia Vera; Rabbits

Topics: Hemorrhagic Disorders; Humans; Leukemia, Radiation-Induced; Leukopenia; Methods; Osteosclerosis; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis; Radiotherapy; Radiotherapy Dosage; Remission, Spontaneous; Thrombocytopenia; Time Factors

Topics: Bone Neoplasms; Contrast Media; Germany; Humans; Iodine Radioisotopes; Leukemia, Radiation-Induced; Liver Neoplasms; Lung Neoplasms; Mining; Neoplasms, Radiation-Induced; Pacific Islands; Paranasal Sinus Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioactive Fallout; Radiotherapy; Radium; Radon; Spondylitis, Ankylosing; Thorium; Thorium Dioxide; Thyroid Neoplasms; United States; Uranium

To compare by a prospective study in high risk polycythemia vera (PV) patients 33P alone and 32P followed by low-dose hydroxyurea (HU) maintenance therapy. Toxicity, efficiency, and leukemogenic potential were studied.. 483 patients with a documented PV, aged more than 65 years at diagnosis, were included between 1980 and 1996 in a prospective study comparing 32P alone and 32P followed by low-dose HU maintenance therapy. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months.. Treatments were well tolerated, but chronic leg ulcers were observed in the maintenance therapy arm. The risk of leukemia was about 15% at the 15th year in the group of patients treated by 32P alone, but reached 30% in the group receiving maintenance therapy. In both arms, there was no significant correlation between occurrence of leukemia and the total dose of 32P. There was a correlation between the leukemic risk and disease severity, estimated on the frequency of relapse. Cancer occurrence was slightly higher than expected in the maintenance arm. HU treatment did not protect against progression to myelofibrosis, probably due to the lack of maintenance of an efficient myeloid or megakaryocytic suppression. Median life-span was slightly shorter in the group receiving HU maintenance. In all cases, life-span was only one year lower than that observed in the reference population.. For all these reasons, we suggest the us of 32P alone in elderly patients; complementary chemotherapy should only be prescribed in the cases with short-term relapse, and late resistance to 32P.

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Female; Humans; Hydroxyurea; Leukemia; Male; Phosphorus Radioisotopes; Polycythemia Vera; Prospective Studies; Risk Factors; Survival Rate

Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting <2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.

Topics: Actuarial Analysis; Aged; Alkylating Agents; Combined Modality Therapy; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Risk; Survival Analysis; Vascular Diseases

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

The present report is based on an analysis of the evolution of 720 cases of Polycythaemia vera treated with pipobroman and 624 cases treated with hydroxyurea. General modes of treatment are identical for the two drugs, consisting of initial therapy at relatively high dose aimed at obtaining complete remission and maintenance therapy essential to conserve the improved clinical status. Both types of treatment must be adapted to suit the patient. Complete remission is achieved in 95 to 100% of cases with pipobroman and in 80 to 90% of cases with hydroxyurea. Incidents which may occur during initial therapy include cytopenia, more frequent and severe under treatment with hydroxyurea, rare transitory digestive troubles and cutaneous and mucous eruptions. Subject to control of the blood cell count every three to four months, maintenance therapy may be continued for many years and while the time lapse is as yet insufficient for hydroxyurea, resistance to pipobroman does not appear to develop even after more than 20 years of treatment. Although neither of these two drugs entirely avoids the occurrence of acute leukaemia which appears in 5 to 8% of subjects irrespective of the duration of therapy, on the contrary to observations in patients treated by bleeding alone, myeloid splenomegaly with myelofibrosis is rare and develops in no more than 2% of cases. The frequency of visceral cancers is not increased by either drug. Provided Polycythaemia vera is maintained in complete remission, thrombotic accidents occur no more often than in a normal population of the same age bracket.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Bloodletting; Combined Modality Therapy; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Splenomegaly; Vascular Diseases

The current results of prospective protocols initiated by the Polycythaemia Vera Study Group are presented. These results help to define the best choice of treatment in accordance with the risk factors.

Topics: Bloodletting; Chlorambucil; Clinical Trials as Topic; Humans; Hydroxyurea; Phosphorus Radioisotopes; Polycythemia Vera; Random Allocation

In 293 patients with previously untreated polycythaemia vera, two different treatment modalities were randomized: 32P (0.5-1 mCi/10 kg at diagnosis and for each overt relapse) versus busulfan (4-6 mg/day during 4-8 weeks, with re-administration at relapse). Duration of remission was significantly longer after busulfan (median not equal to 4 years) than after 32P (median not equal to 2 years). Moreover, overall survival was slightly but significantly longer in patients treated with busulfan, with a trend towards increased mortality related to vascular complications or secondary cancers in the 32P group.

Topics: Aged; Busulfan; Clinical Trials as Topic; Humans; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Random Allocation

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.

Topics: Acute Disease; Age Factors; Bloodletting; Chlorambucil; Combined Modality Therapy; False Positive Reactions; Follow-Up Studies; Gastrointestinal Neoplasms; Gout; Hematocrit; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Count; Polycythemia Vera; Prospective Studies; Pruritus; Skin Neoplasms; Thrombosis

The PVSG study is unique in that it is prospective and composed of 432 patients randomized to three treatment arms. This study also provides the opportunity for serial studies of numerous sequential biopsies. Large numbers of cases with sequential biopsies covering the entire long course are essential to appreciate the full spectrum of tissue changes in this disease. The PVSG was initiated in 1967 and in mid-1985 approximately one third of the patients are alive and on protocol. For these reasons, the results must still be considered preliminary. Pretreatment biopsies from patients randomized in the PVSG have been analyzed for total cellularity, megakaryocyte concentration, and reticulin content. Considerable variation in these elements was found in these biopsies. Sequential posttreatment biopsies from these patients have also been studied and correlated with the clinical course of the disease. None of the morphologic parameters analyzed was shown to be of prognostic significance. Early in the course of PV the marrow reticulin content is almost always normal. The length of the developmental stage is unknown and the precise timing of the clinical onset may be difficult. Therefore, the 11% of patients that showed a significant increase in reticulin on initial evaluation may have had PV longer than was indicated clinically. If large numbers of sequential biopsies are studied, an increase in reticulin content can frequently be demonstrated during the active phase of the disease and before the onset of the spent phase. Currently 39 patients (9%) have developed the spent phase, or PPMM. PPMM occurred in about the same incidence in the patients treated with myelosuppressive therapy as by phlebotomy alone, the spent phase occurring in 16 patients treated by phlebotomy alone, 11 with chlorambucil, and 12 with 32P. The course of the reticulin fibrosis is slowly progressive. There is some evidence for regression in a few patients in the erythrocytotic phase, but sampling variation cannot be completely ruled out. At this time in the study, AL has developed in 37 patients (8.6%). The incidence of AL is quite low in the phlebotomy group (three cases). Presumably this represents the natural incidence in PV unmodified by therapeutic agents. The frequency is approximately equal and quite high in the chlorambucil and 32P groups. There are 19 cases in the chlorambucil-treated group and 15 in the 32P-treated group. The leukemias that developed in the PV patients occurred ei

Topics: Acute Disease; Aged; Bloodletting; Bone Marrow; Bone Marrow Cells; Chlorambucil; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Leukemia; Lymphoma; Megakaryocytes; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Reticulin; Retrospective Studies

Thirty-one patients with essential thrombocythemia were randomized to receive either melphalan or radioactive phosphorus as myelosuppressive therapy. Twenty-seven patients were evaluable for response. Of 13 patients treated with melphalan, 11 had a complete response (platelet count less than 450,000/mm3) at 3 and 6 months. This response rate was significantly better than the response to radioactive phosphorus. The response rates were similar at 12 months. No significant toxicity was observed with either regimen.

Topics: Aged; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocythemia, Essential

In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.

Topics: Acute Disease; Chlorambucil; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Leukemia; Phlebotomus; Phosphorus Radioisotopes; Polycythemia Vera; Prospective Studies; Random Allocation; Time Factors

Between 1967 and 1978 a Phase III cooperative study was performed in polycythaemia vera (PCV) patients who had not been treated previously with any specific therapy other than phlebotomy. 293 patients were included and allocated at random for either radiophosphorus therapy (146) or busulphan treatment (147). Additional phlebotomies were indicated in both groups, to keep the haematocrit at 42-47%. 285 patients were evaluable after the study was completed, of whom 50% have an 8-year follow-up. Both groups were comparable with respect to age, clinical symptoms and haematological parameters immediately before randomization. The duration of the first remission and the overall survival were significantly better in the busulphan group. This difference remains significant after correction for differences between the two groups with respect to sex-ratio and phlebotomy before and the start of therapy. Busulphan induced a longer first remission (P less than 0.001) and a longer overall survival (P less than 0.02).

Topics: Aged; Bloodletting; Busulfan; Clinical Trials as Topic; Female; Humans; Male; Phosphorus Radioisotopes; Polycythemia Vera; Random Allocation

Topics: Adult; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

In 109 patients with polycythemia vera, previously treated by 32P without maintenance therapy, a trial was carried out to determine the best way to reduce the number of injections needed. Chlorambucil and hydroxy-urea have been used to lengthnen the remission. Both of them are well tolerated and compatible with follow-up at reasonable time intervals. Chlorambucil maintenance increases the mean duration of remission by 12 months, the best results being observed when the drug was used continuously, instead of an intermittent (3 consecutive days every fortnight) schedule. Hydroxy-urea does not produce statistically demonstrable advantage whatever it is given, continuously or intermittently. Our study shows that, if a long-term cooperative study of the possible advantage of maintenance therapy in P.V. was undertaken in the future, low-dosage maintenance by chlorambucil could be the treatment of choice.

Topics: Chlorambucil; Drug Tolerance; Humans; Hydroxyurea; Long-Term Care; Phosphorus Radioisotopes; Polycythemia Vera; Time Factors

Topics: Busulfan; Clinical Trials as Topic; Female; Humans; Leukemia; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Remission, Spontaneous; Sex Factors

Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU).. On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk.. Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P(32)), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P(32) greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation.. The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P(32) and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Case-Control Studies; Female; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Logistic Models; Male; Middle Aged; Myelodysplastic Syndromes; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Risk Factors; Thrombocythemia, Essential

Topics: Bone Neoplasms; Clinical Trials as Topic; Humans; Medical Oncology; Neoplasm Metastasis; Nuclear Medicine; Phosphorus Radioisotopes; Polycythemia Vera; Radiopharmaceuticals; United Kingdom

The prevailing attitudes regarding diagnostic and therapeutic procedures in patients with polycythaemia vera (PV) among Swedish haematologists were surveyed by way of a mailed questionnaire in August 2002. Among diagnostic procedures frequent use is reported for arterial O(2) saturation, spleen size determination, bone marrow histology, serum erythropoietin, serum cobalamins and leukocyte alkaline phosphatase score, while direct determination of the red blood cell mass is used infrequently (seldom or never by 82%). Among therapeutic modalities hydroxyurea and phlebotomy alone were most frequently used. The (32)P therapy was used at least sometimes by 57% of the physicians, and more widely in the university clinics. Anagrelide and alfa-interferon was used in a minority of patients only. The use of prophylactic acetylsalicylic acid was very variable. The majority of the physicians had an aim for their phlebotomy treatment at a level of 0.45 or less, but 21% used a level of 0.46-0.49 and 8% a level of 0.55-0.60 (in younger patients). The platelet level, at which myelosuppressive therapy was initiated, also varied, from 400 x 10(9)/L to >1500 x 10(9)/L. It can be concluded that in practical clinical work in Sweden the diagnosis of PV is established by frequent use of serum erythropoietin, bone marrow examination and spleen size determination. The use of different therapeutic modalities is very variable. Many physicians carry out their phlebotomy treatment with less intensity compared with national and international recommendations.

Topics: Antineoplastic Agents; Attitude of Health Personnel; Erythrocyte Volume; Erythropoietin; Health Care Surveys; Humans; Interferon-alpha; Phlebotomy; Phosphorus Radioisotopes; Physicians; Polycythemia Vera; Surveys and Questionnaires; Sweden

Topics: Europe; Humans; Myeloproliferative Disorders; Nuclear Medicine; Patient Selection; Phosphorus Radioisotopes; Polycythemia Vera; Radiopharmaceuticals; Radiotherapy; Societies, Medical; Thrombocythemia, Essential; Treatment Failure; Treatment Outcome

The risk of development of cancer, and more specifically acute leukaemia, after use of phosphorus-32 in patients with polycythaemia vera has been recognised for approximately 40 years. As a consequence of this risk, the indications for, and contraindications to, 32P are unclear in the physician's mind. This paper aims to clarify the problem. The relation between polycythaemia vera and leukaemia is explored and the question of whether chemotherapy represents an alternative to 32P is discussed. From the results obtained to date, two clear conclusions can be drawn: First, whatever the age of the patient, phlebotomy must be used to avoid the menace of vascular complications before the institution of basic treatment, but it cannot be used as the sole form of treatment. Second, 32P treatment retains an important role at least when chemotherapy fails and in elderly patients (>70 years).

Topics: Age Distribution; Aged; Comorbidity; Female; Humans; Incidence; Leukemia; Male; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Sex Distribution; Survival Rate

The frequent side effects of Hydroxy-Urea and the non-exceptional risk of leukemia and cancer in Polycythemia Vera treated for a long time by Hydroxy-Urea allow to conclude that Hydroxy-Urea is not an innocent drug. In a prospective trial of 150 patients with a median follow up of nine years, Hydroxy-Urea given alone induced side effects in 29% of patients necessitating to stop treatment in half of cases. The percentage of leukemia or myelodysplasia is 6.7% with an actuarial risk of leukemic transformation of 10% at 13 years. In an other prospective trial in 181 aged patients Hydroxy-Urea was given as maintenance therapy after 32P treatment. The median follow-up in that study is also of nine years. Side effects are observed in 13% of cases. A two fold increase of the leukemic risk was observed in the maintenance arm of the trial: 11 versus 19% at ten years, 14 vs 30% at 12 years, 16 vs 35% at 15 years because of the leukemogenic effect of Hydroxy-Urea in maintenance therapy we stopped including new patients in this arm of the trial.

Topics: Aged; Alopecia; Combined Modality Therapy; Cystitis; Erectile Dysfunction; Female; Fever; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leg Ulcer; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neural Tube Defects; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prospective Studies; Risk; Safety; Stomatitis, Aphthous

Polycythemia vera (PV) and essential thrombocytosis (ET) are clonal chronic myeloproliferative disorders originating from a multipotent stem cell. Bone marrow examinations reveal chromosomal abnormalities in 15-43% of PV patients and 5% of ET patients, but no specific recurring abnormality has been found to date. We aimed to find cytogenetic aberrations in PV and ET by comparative genomic hybridization (CGH), a relatively new molecular cytogenetic technique. In this study, CGH analysis was performed on peripheral blood leukocytes of 12 PV patients and 8 ET patients. One patient (8.3%) with PV had an abnormal karyotype with a deletion in 7q11.2 and one patient with ET (12.5%) had a gain in 18p. Peripheral blood analysis by CGH revealed a low frequency of cytogenetic abnormalities in PV and ET patients. However, using CGH we were able to detect two cytogenetic aberrations that were not reported previously in these disorders.

Topics: Aged; Aged, 80 and over; Chromosome Aberrations; Female; Humans; Hydroxyurea; Male; Middle Aged; Nucleic Acid Hybridization; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocytosis

In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.

Topics: Adult; Aged; Busulfan; Erythropoietin; Female; Humans; Hydroxyurea; Immunosuppressive Agents; Interferon-alpha; Male; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera

Modern treatment has dramatically improved the prognosis for patients with polycythaemia vera (PV). Here a patient is described who has been followed and treated for PV for over 30 years, demonstrating that very long term survival can be achieved in PV. However, effective treatment modalities such as radioactive phosphorus, alkylating agents and, most recently, hydroxyurea, have all been shown to increase the risk to develop acute leukaemia when used in the treatment of myeloproliferative disorders. Hopefully, the prolonged survival of this patient may help to emphasize the need to use non-leukaemogenic agents when treating younger PV patients.

Topics: Adult; Busulfan; Female; Humans; Hydroxyurea; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Survivors; Treatment Outcome

Topics: Bloodletting; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy Dosage

This article, by two of the late John H. Lawrence's fellows of the 1940s, traces the development of the knowledge of polycythemia vera from Vaquez, who wrote the first description of this disease, and Osler, who recognized it as "a new clinical entity," through John H. Lawrence and the use of 32P as a treatment for polycythemia vera, to the formation of French and Italian polycythemia study groups. In particular, the history of polycythemia vera after the Second World War, and its more recent history, can be traced through the development of an algorithm for evaluating an elevated hematocrit and the development of the first (O1) protocol of the Polycythemia Vera Study Group (PVSG), a randomized trial of the efficacy of 32P, chlorambucil, and phlebotomy for treating polycythemia vera. It was in 1948, only 9 years after the first use of 32P for treating polycythemia vera, that Byron Hall reported the occurrence of acute leukemia following this use of the isotope. This led to the formation of the PVSG. After completing enrollment of patients in the first protocol of the PVSG, an attempt to find a replacement for 32P as a myelosuppressive agent led to the testing of hydroxyurea as a putative non-leukemogenic drug for this purpose. However, the use of hydroxyurea for treating polycythemia vera is coming into question, as is the ability to maintain patients with phlebotomy alone. The PVSG as such no longer exists as an operational group; its files are maintained at the Mount Sinai School of Medicine in New York City. However, the French group created for the study of polycythemia vera has had a consensus conference, and the Italian group has developed a low-dose aspirin protocol for treating the disease.

Topics: Aspirin; Blood Volume; Controlled Clinical Trials as Topic; Female; Hematocrit; History, 19th Century; History, 20th Century; Humans; Hydroxyurea; Male; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera

259 patients with primary proliferative polycythaemia (PPP) and idiopathic thrombocythaemia (IT) have been treated with 32P over the last 15 years. Complete follow-up data were obtained in 238 patients. PPP was the diagnosis in 183 patients and 76 patients had IT. The sex ratio in PPP was male/female 1.1:1 and in IT 1:1.4. Patients' ages ranged from 28 to 95 years (median 72 years). The number of 32P administrations per patient ranged from 1 to 13 (median 2) and the total administered activity per patient ranged from 81.4 to 4162 MBq (median 496 MBq). The outcome showed a normalization of the full blood count in 50% of patients after a single administration of 32P and in 73% after two treatments. 13 patients (5.5%) developed myelofibrosis; 18 (7.6%) developed leukaemia while other cancers arose in 19 patients (8%). 32P therapy proved to be of particular value in the elderly. 32P is easy to administer and is cost effective, compared with the alternative of chemotherapy where good compliance and frequent hospital visits are required.

Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera; Retrospective Studies; Thrombocythemia, Essential; Treatment Outcome

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Topics: Acute Disease; Anemia, Refractory, with Excess of Blasts; Busulfan; Cell Transformation, Neoplastic; Chlorambucil; Cohort Studies; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Hydroxyurea; Incidence; Interferon-alpha; Leukemia; Leukemia, Radiation-Induced; Male; Melphalan; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Preleukemia; Primary Myelofibrosis; Retrospective Studies; Ribonucleotide Reductases; Risk; Thrombocythemia, Essential

Myeloproliferative disorders (MPD) are prone to modification and evolution during the progression of the disease. While post-polycythemia myeloid metaplasia and chronic myelogenous leukemia following polycythemia vera have been frequently described, no report is available about the evolution of polycythemia vera into essential thrombocythemia. Our case is probably the first report on this occurrence. In the course of a fortuitous observation of electrocardiographic alterations, a diagnosis of polycythemia vera was ruled out in accordance with polycythemia vera study group criteria. At the time of diagnosis, RBC was 6 x 10(12)/L, WBC 15 x 10(9)/L, Ht 59% and platelets 1000 x 10(9)/L. The patient was treated with phlebotomies and radioactive phosphorus achieving a good remission or the disease. Five years later, platelets rose to over 3300 x 10(9)/L without significant modification or RBC, WBC and Ht. The restaging or the disease was consistent for an essential thrombocythemia. In particular, RBC mass was within normal levels. During the last ten years, the patient has been followed recurrently and the blood picture remained stationary, without an increase in the hematocrit but with a platelet count between 658 and 800 x 10(9)/L. We conclude that this report may complete data concerning the evolution of MPD in others.

Topics: Aged; Aged, 80 and over; Alkylating Agents; Busulfan; Hematocrit; Humans; Leukocyte Count; Male; Phosphorus Radioisotopes; Platelet Count; Polycythemia Vera; Thrombocythemia, Essential; Time Factors

Topics: Administration, Oral; Aged; Female; Humans; Leukemia, Myeloid, Acute; Male; Phosphorus Radioisotopes; Polycythemia Vera; Risk Factors

For 366 patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) diagnosed 1971-1990, oral administration of 32-P was used as myelosuppressive treatment. Retreatment was not restricted to any defined interval and the number of treatments or the total dose were not limited. For 107 patients, follow-up was > 10 years. 15 of these presented with life-threatening occlusive vascular symptoms and their survival was short. For the remaining 92 patients 5-yr survival was not significantly worse than for a Swedish population matched for age and sex. Survival at 10 yr was lower, 51% versus 66% expected. Acute myeloid leukaemia (AML) was diagnosed in 11 of the 107 patients (10.3%). In the whole material of 366 patients, 17 have developed AML with a median time of 8.5 yr from start of treatment. There was a maximum incidence of 4% per yr after 8-12 yr. Later, the incidence decreased. The median annual dose of 32-P for the AML patients was 100 MBq and was not significantly larger than for a matched control group surviving without AML, 96 MBq. The results are compared with reports on PV or ET patients treated with busulphan (Bu) or hydroxyurea (HU). With comparable periods of follow-up there are no indications that an adequate myelosuppression with oral 32-P will be associated with shorter survival or higher incidence of AML than treatment with Bu or HU. It is concluded that, for the time being, oral administration of 32-P is an acceptable standard treatment in PV and ET.

Topics: Administration, Oral; Aged; Busulfan; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoplasms, Second Primary; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocytosis; Time Factors

The follow-up of a 93-year-old-patient with polycythaemia vera (PV) diagnosed in 1977 is presented. The patient accidentally received a ten-fold overdose of radioactive P32 due to an incorrectly labelled vial. 14 days after the administration of the overdose of P32, the patient was admitted to the University Hospital of Zurich with bone marrow aplasia. She recovered from the aplasia within 6 weeks. During the following 15 years she has suffered no relapse nor developed leukemia as a secondary complication.

Topics: Aged; Aged, 80 and over; Bone Marrow Diseases; Drug Overdose; Female; Follow-Up Studies; Humans; Leukopenia; Medication Errors; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocytopenia

The very-long-term follow-up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotomy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly. In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.

Topics: Aged; Bloodletting; Chlorambucil; Follow-Up Studies; Humans; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Treatment Outcome; Vascular Diseases

With the very long life expectancy of Polycythaemia Vera late complications are often observed: progressive resistance to treatment, bad tolerance to maintenance by phlebotomy, progression towards myelofibrosis. Resistance to phosphorus 32 is reflected by a progressive reduction in the duration of remission and by a gradually decreasing remission rate. A complete resistance appears after a mean duration of disease of 7 years. In the maintenance treatment by hydroxyurea, there is a secondary resistance in one third of cases with a poor control of the excess platelets. Resistance to Pipobroman is less frequent (10%). The phosphorus resistance could be delayed by addition of maintenance treatment by Hydroxyurea. In the presence of resistance to 32 P, Hydroxyurea and Pipobroman often remain effective. In the case of resistance to Hydroxyurea or Pipobroman, we have several possibilities: inversion of chemotherapy, other chemotherapy as Busulfan, 32 phosphorus. Intolerance of phlebotomy as baseline treatment is almost constant. Three complications lead to discontinuation of phlebotomy: development of cardiovascular complications, raised platelet count to above 800,000 and often more than 1 million, progressive increase in the size of the spleen with appearance of signs of myeloid splenomegaly. Exclusive phlebotomies are not indicated as baseline treatment of Polycythaemia Vera. The progression towards myelofibrosis (spent phase, post polycythaemia myeloid splenomegaly) increases with the duration of the disease and the frequency of transformation differs according to the type of treatment. The time to transformation is much shorter in the patients treated by phlebotomy. The transformation towards myelofibrosis is demonstrated by bone marrow biopsy and isotope investigations (bone marrow scintigraphy and kinetic by iron 59 and chromium 51).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bloodletting; Cardiovascular Diseases; Chronic Disease; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis

The treatment of primary proliferative polycythaemia (polycythaemia rubra vera) may include radioactive phosphorus (P32) in conjunction with venesection. Acute leukaemia or carcinoma can be associated with the use of P32. We present a case of primary proliferative polycythaemia treated by repeat venesection together with P32 whose follow-up was complicated by the development of malignant neuroblastoma.

Topics: Bloodletting; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neuroblastoma; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Hematologic Diseases; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocytosis

We have evaluated 230 patients with myeloproliferative disorders treated in the last 15 years with 32P. None of the patients affected by essential thrombocythaemia developed haematological complications. In the larger group of polycythaemia patients (214 subjects) only 38 patients (17 males and 21 females) developed complications. 60.5% of these subjects had a minor complications: 1.8% showed a thrombocytopenia lower than 100.10e9/lt, 2.3% anaemia with Hb lower than 10 g%, 2.6% leukopenia lower than 40.10e9/lt and 2.3% a pancytopenia. All these complications were transient and eventually treated with limited blood transfusions. We could not identify a correlation between the dose used and the development of such complications. We noted only that the occurrence of anaemia, given a similar dose, was more frequent in females. Only 7% of all patients presented a major complication after 32P administration. In this case too, there was no correlation with the dose administered. Myelofibrosis and chronic myeloid leukaemia resulted to be the more frequent complication (9 out of 15) but we could not clarify if they represented a natural evolution of polycythaemia vera or were due to the treatment with 32P. Acute leukaemia developed only in 5 patients and again we could not recognized a correlation with the dose administered. Moreover, the time from the diagnosis of polycythaemia vera the onset of acute leukaemia ranged widely. 32P has a definite effect on the prevention of thrombotic and haemorrhagic complications in polycythaemia patients since it prolongs their life but it also increases the incidence of acute leukaemia.

Topics: Anemia; Female; Follow-Up Studies; Hematologic Diseases; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukopenia; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Thrombocytopenia

Natural killer (NK) cell number and activity were measured in 26 patients with myeloproliferative disorders and the results were compared with 16 age-matched control patients. The percent of Leu-11b-positive cells was 11% +/- 3% in the patients, compared with 12% +/- 4% in the control patients. Ten of 26 patients, however, had NK activity lower than all of the control values at three different effector to target cell ratios (E:T) (P less than 0.005). The values of those patients with low unstimulated NK activity remained low despite stimulation with interleukin-2 (IL-2) or alpha-interferon (alpha-IFN), whereas the values of those patients with normal unstimulated activity responded to IL-2 and alpha-IFN like the control patients. Three of the ten patients with low NK activity had a history of malignant neoplasms. None of the 16 patients with normal NK activity had a history of malignant neoplasms (P less than 0.05). We conclude that patients with myeloproliferative disorders frequently have low endogenous NK cell activity in vitro. The dysfunction of the NK system appears to be intrinsic because the relative number of NK cells was similar to control values and the response to stimulation with IL-2 and alpha-IFN was suboptimal. There may be a relationship between low NK activity and the development of malignant disease in such patients.

Topics: Bloodletting; Humans; Hydroxyurea; Interferon Type I; Interleukin-2; Killer Cells, Natural; Myeloproliferative Disorders; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Thrombocytosis

Between March 1970 and February 1987, radiophosphorus (32P) was used to treat bone marrow disorders in 6 dogs; 4 had polycythemia vera and 2 had essential thrombocythemia. Activities of 32P given initially ranged from 2.4 to 3.3 mCi/m2. Four dogs responded well to 32P treatment, with gradual resolution of high RBC or platelet counts. Two of these dogs died of intercurrent disease unrelated to their bone marrow disorder, before blood counts could be stabilized. Two dogs did not respond to the initial 32P treatment nor to additional treatments with 32P, and had clinical signs and blood counts stabilized by use of phlebotomy or chemotherapeutic agents. We reviewed and analyzed 5 other cases of bone marrow disorders in dogs treated with 32P and included the findings from their records with the records of our 6 dogs in this retrospective analysis. Of the 8 dogs with polycythemia vera treated with 32P, 5 were given a single treatment that controlled clinical signs and blood counts for the remainder of the follow-up period. Of the 3 dogs treated for thrombocytosis with 32P, 2 had blood counts that responded to a single treatment.

Topics: Animals; Dog Diseases; Dogs; Female; Male; Phosphorus Radioisotopes; Polycythemia Vera; Retrospective Studies; Thrombocythemia, Essential

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 I

Topics: Aged; Aged, 80 and over; Antibody Formation; Female; Goiter, Nodular; Humans; Iodine Radioisotopes; Lectins; Leukocyte Count; Leukopenia; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

The fate of the polycythaemic patient depends on the treatment employed which may determine the nature of the transformation commonly occurring late in the course of the disease. Treatment is, on the other hand, aimed at prevention of the most frequent complications, that is of thromboembolic processes. In the last 30 years the authors treated a total of 118 PV patients, of whom 60 have died. Initially 32P treatment was applied, which was modified later, because of acute leukaemia that had occurred in 9% of the treated cases, to a single 5 mC 32P+Myelobromol (DBM) treatment. Still later only DBM was administered in the form of stosstherapy (2500 mg per day over a period of 4 days). In the latter two groups, acute leukaemia occurred as few as two cases. The course of untreated polycythaemia vera is characterized by transformation into another myeloproliferative disease. This phenomenon occurs in 50% of the cases on drastic treatment and in patients treated with 32P. Of the patients who were alive when the report was finished 35% had been free of complications, while 5.2% were suffering from chronic granulocytic leukaemia (CGL), 34.5% from sclerotic osteo-myelofibrosis (OMF-SC) and 3.4% from chronic megakaryocytic granulocytiv leukaemia (CMGL). Of the 60 patients having died, 15% had suffered from other complications being predominantly of vascular nature. 11.8% of them died of AML, 10% of CGL, 26.7% of OMF-SC and 26.7% of CMGL. The terminal stage was characterized, in the majority of cases, by blastic crisis. Based on their own results and literary data authors recommend DBM treatment besides the indispensable phlebotomy.

Topics: Adult; Aged; Aged, 80 and over; Chlorambucil; Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Middle Aged; Mitobronitol; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Busulfan; Chlorambucil; Combined Modality Therapy; Erythrocyte Count; Erythropoiesis; Humans; Leukemia; Phosphorus Radioisotopes; Platelet Count; Polycythemia Vera

The influence of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of 32P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. 32P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

Topics: Aged; Aged, 80 and over; Blood Cells; Female; Humans; Immunoglobulins; Leukocyte Count; Lymphocytes; Male; Middle Aged; Osmolar Concentration; Phosphorus Radioisotopes; Polycythemia Vera

Fifteen cytoplasmic erythrocyte enzyme activities were determined in patients with polycythemia vera (PV), iron deficiency anemia (IDA), and a group of healthy volunteers. Among the PV patients, the erythrocyte enzyme activities were compared between 2 groups: patients treated solely with phlebotomy and patients treated with phlebotomy, Myleran (busulfan) and/or radioactive phosphorus 32P. Significant reduction in glutathione reductase activity was found in the PV group of patients. This activity was normalized by the addition of flavin adenine dinucleotide. In contrast to previous reports, no other enzyme activity was found to be significantly reduced. The activities of the enzymes known to be age-dependent were significantly elevated in all the groups tested except for phosphofructokinase and 3-phosphoglycerate mutase. The former was not elevated in any of the groups studied, while the latter was elevated only in the group of patients treated with Myleran and/or 32P. It was concluded that glutathione reductase (GR) deficiency is the only acquired enzyme deficiency in our group of PV patients and that radiation and chemotherapy did not induce further reduction in the activities of any of the enzymes tested. The possible involvement of GR deficiency in the etiology of the red cell life span shortening was discussed.

Topics: Anemia, Hypochromic; Bloodletting; Busulfan; Combined Modality Therapy; Cytoplasm; Erythrocyte Aging; Erythrocytes; Female; Flavin-Adenine Dinucleotide; Glutathione Reductase; Humans; Male; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Acute Disease; Antigens, Neoplasm; Bloodletting; Chlorambucil; Chromosome Aberrations; Chromosome Disorders; Humans; Hydroxyurea; Leukemia; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Prospective Studies; Retrospective Studies; Time Factors

Topics: Adult; Aged; Antineoplastic Agents; Aziridines; Busulfan; Humans; Middle Aged; Mitobronitol; Phosphorus Radioisotopes; Polycythemia Vera; Retrospective Studies; Thiazolidines

Topics: Aspirin; Dipyridamole; Female; Hemorrhage; Humans; Male; Phosphorus Radioisotopes; Platelet Aggregation; Platelet Count; Polycythemia Vera; Thrombosis

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

We report on a follow up in 23 patients with primary thrombocytosis treated with two different doses of 32phosphorus phosphate (32P). Ten patients with essential thrombocytosis (ET) received 2 mCi and 13 patients with polycythemia vera (PV) received the standard dose of 0.1 mCi/kg b.w. The patients were listed as having a complete response (CR), partial response (PR) or no response (NR) considering platelet count at 3 and 12 months after 32P injection. The results indicate the existence of a clear correlation of the rate of remission with the 32P injected dose. PV patients show, in fact, a percentage of complete remission higher than ET patients. However, the use of higher doses induces more early and long-term complications.

Topics: Adult; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Platelet Count; Polycythemia Vera; Thrombocythemia, Essential; Thrombocytosis

Topics: Bloodletting; Busulfan; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis

Topics: Aged; Erythema; Follow-Up Studies; Humans; Male; Paraneoplastic Syndromes; Phosphorus Radioisotopes; Polycythemia Vera; Thiophenes; Ticlopidine

A 7-year-old, crossbred, desexed bitch had a fluctuating illness of more than 6 months duration, with signs of inappetence, reduced exercise tolerance, restlessness, panting, black diarrhoea, and red eyes and ears. Haematological examination disclosed persistent polycythaemia, reticulocytosis, normoblastaemia , and normal total plasma protein concentration when not dehydrated. Splenomegaly was present, but there was no evidence of significant pulmonary, cardiac or renal disease on physical, radiographic or electrocardiographic examination. Further investigations revealed normal arterial Po2 and oxygen saturation, and increased total erythrocyte volume. Primary polycythaemia was diagnosed. The dog was rendered anaemic by bleeding, then treated with a single injection of radioactive phosphorus. The patient has had no recurrence of signs and remains well 50 months later.

Topics: Animals; Bloodletting; Combined Modality Therapy; Dog Diseases; Dogs; Female; Humans; Male; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Cell Count; Bloodletting; Diagnosis, Differential; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Kidney Diseases; Lung Diseases; Oxygen; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Bloodletting; Cell Separation; Combined Modality Therapy; Erythrocyte Count; Humans; Phosphorus Radioisotopes; Polycythemia Vera

Red cells of polycythaemia vera (PV) patients have a significantly higher rate of electrophoresis than red cells of normal controls and stress polycythaemia patients. The highest increment in the electrophoretic velocity was noted for PV patients treated with phlebotomy or hydroxy urea. The red cells of PV patients treated with 32P and those that progressed to myeloid metaplasia showed a normal rate of electrophoresis. We assume that the increased negative charge found on the red cells of PV patients is typical of the abnormal clone proliferating in this disease. The normal electrophoretic velocity found for the red cells of the 32P treated patients or those that progressed to myeloid metaplasia might indicate that the circulating red cells of these patients are no longer descendants of the abnormal stem cell.

Topics: Bloodletting; Cell Movement; Erythrocytes; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Stress, Physiological

Two patients with polycythemia vera received intravenously an accidental tenfold overdosage of radiophosphorus therapy (60 and 50 mCi 32P, respectively). In both patients, the occurrence of hemorrhagic complications 3 wk after the 32P medication led to detection of the error and referral to our hospital. Upon admission they showed an agranulocytosis, severe thrombocytopenia, and bone marrow aplasia. In both cases, spontaneous recovery of the hematopoiesis was observed from day 40 posttreatment onward. In one patient, a slow but ultimately complete normalization of blood counts and marrow morphology took place, whereas in the other, a mild thrombocytopenia persists. Nearly 5 yr after the accidental overdosage, both patients are clinically well. Symptoms of polycythemia vera have not reappeared up to now. Attempts were made to evaluate the radiation dose absorbed by the bone marrow. In the first patient, the daily 32P excretion was determined from day 22 to day 60, whereas in the other patient a whole body count was performed on day 78 after administration. From these results, an approximate cumulative bone marrow dose of 10 Sv (1000 rem) could be calculated.

Topics: Aged; Agranulocytosis; Bone Marrow; Bone Marrow Cells; Female; Humans; Medication Errors; Phosphorus Radioisotopes; Polycythemia Vera; Radiation Dosage; Radiation Injuries; Remission, Spontaneous; Thrombocytopenia

An example of chocked disk of 3-4 diopters (right eye) and 4-5 diopters (left eye) in a patient with cerebral alteration (encephalomalacia respectively bleeding) suffering from polycythemia vera is discussed in the light of own observation, literature, differential diagnosis, pathogenesis, and therapy. An internal treatment by radioactive phosphorus and blood-letting gave restitutio fere ad integrum.

Topics: Adult; Bloodletting; Cyanosis; Female; Hemianopsia; Humans; Hyperemia; Papilledema; Phosphorus Radioisotopes; Polycythemia Vera; Retinal Diseases

Basis, indications and results of the endolymphatic therapy with radionuclides, of the selective therapy with radiophosphorus and radiostrontium and of the intraarticular and endocavitary therapy with radiocolloids are described. Future scientific engagement and intensive basic research in radionuclide therapy is required. However, because of the expected therapeutic profit the efforts seem to be justified.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Child; Child, Preschool; Female; Gold Colloid, Radioactive; Humans; Infant; Iodine Radioisotopes; Male; Middle Aged; Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes; Radiotherapy; Radiotherapy Dosage

Topics: Aged; Basal Ganglia; Bloodletting; Cerebral Infarction; Chorea; Female; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Regional Blood Flow; Tomography, X-Ray Computed

Topics: Bone Marrow; Busulfan; Chlorambucil; Cyclophosphamide; Humans; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera

Radiation dose to mouse testis was estimated to be about 1.65 rad per microCi of intravenously injected 32P. This high dose to the organ was due to the incorporation of this isotope into the macromolecules of the testis. Up to 30% of the total testis activity was in DNA molecules. Biologic effects on mouse testis from 32P were determined by testis weight loss and the decrease in the number of sperm heads in the testis. Number of sperm heads reached a minimum of 1.3% of control 36 days after injection of 3.5 microCi/g body weight of 32P. Significant decreases in sperm head counts were observed after as little as 0.2 microCi/g body weight of 32P.

Topics: Animals; DNA; Male; Mice; Phosphates; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radiation Dosage; Sperm Head; Testis

Fifty-one cases of pure, primary erythrocytosis were identified and followed at Hôpital Saint-Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32P. The median duration of the first remission was greater than five years, the mean yearly dose of 32P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods of investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32P therapy.

Topics: Adolescent; Adult; Aged; Female; Humans; Leukocytosis; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Splenomegaly; Thrombocytosis

Topics: Adult; Aged; Blood Volume; Circadian Rhythm; Female; Humans; Iron; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Sex Factors

The therapeutic approach of internally administered radiopharmaceuticals offers the potential to outmode the present approaches of conventional radiation therapy and chemotherapy because of three characteristics: 1. The therapeutic use of radiopharmaceuticals may deliver as much as orders of magnitude larger rad doses than conventional radiation therapy to target tissues, selectively irradiating these tissues internally in one radiation dose. 2. The therapeutic use of radiopharmaceuticals is followed by a lower incidence of leukemia and other cancers. 3. The treatment is comparatively noninvasive and nontraumatic. We can now make this rather strong statement with fairly firm conviction because Na131I has been used since 1946 (33 years) to treat almost a million patients for hyperthyroidism (a) and in approximately 5000 patients for well-differentiated thyroid cancer (b); NaH2PO4(P-32) has been used for 35 years to treat approximately 25,000 patients with polycythemia vera (3-5).

Topics: Forecasting; Humans; Hyperthyroidism; Iodine Radioisotopes; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Phosphates; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Radiotherapy Dosage; Sodium Iodide; Thyroid Neoplasms

Topics: Adult; Aged; B-Lymphocytes; Bloodletting; Female; Graft vs Host Reaction; Humans; Leukocyte Count; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; T-Lymphocytes

Topics: Adult; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

Erythrocytosis in a young Sinhalese man is described. The patient was known to have had a raised Hb and PCV for at least 10 years. Subsequent investigations failed to support the diagnosis of polycythaemia vera or to reveal a cause for secondary polycythaemia. Blood erythropoietin values were raised, but no cause for inappropriate secretion could be identified. Although there was no evidence of erythrocytosis in the family, the findings in this patient appear to be those of a condition which has been called familial polycythaemia. The spleen was unusually large and was associated with hypersplenism and thrombocytopenia. Problems of diagnosis and management are described. Phlebotomy appears to be the treatment of choice, with a regimen of regular venesection for the control of symptoms due to hyperviscosity and vascular occlusion.

Topics: Adult; Blood Cell Count; Blood Viscosity; Bloodletting; Diagnosis, Differential; Erythropoietin; Humans; Hypersplenism; Male; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Radionuclide Imaging; Thrombocytopenia

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adult; Aged; Aziridines; Female; Humans; Male; Middle Aged; Organophosphorus Compounds; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotope Teletherapy; Radiotherapy Dosage; Recurrence; Remission, Spontaneous

Topics: Acute Disease; Adult; Aged; Bloodletting; Busulfan; Evaluation Studies as Topic; Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Mercaptopurine; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Thromboembolism; Veins

Eleven patients have been observed with clinical features of both polycythaemia vera and myelofibrosis. Detailed follow-up and repeated haematological and isotopic investigations, including the assessment of erythropoietic distribution by 52Fe scanning, over a 10 year period, have indicated that patients who initially present with this syndrome may remain in a steady state for several years and that this transitional syndrome does not necessarily imply an active or irreversible transformation into classical myelofibrosis. Therapy with iron, folic acid, alkylating agents, splenectomy or splenic irradiation may reduce the extramedullary component of myeloproliferation and allow occasional patients to revert to more classical polycythaemia vera. Radioactive phosphorus (32P) therapy may be inappropriate in polycythaemic patients with dominant extramedullary erythropoiesis, as this form of therapy has a preferential medullary action and may selectively encourage extramedullary myeloproliferation.

Topics: Adult; Aged; Blood Cell Count; Busulfan; Female; Folic Acid; Follow-Up Studies; Humans; Iron; Male; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis

During the last 12 years, 86 apparently primary polycythemias have been observed in subjects less than 40 years old. In twelve of them a non-suspected cause has been found (seven abnormalities of the hemoglobin function). In 43 cases, all males, the erythrocytosis (red cell volume more than 36 ml/kg) was pure and stable, without any complication; this "benign erythrocytosis" probably depicts extreme values of the normal distribution of the red cell mass. In 31 cases, the disease had criteria similar to those of polycythemia vera observed in older patients; in 12 of these cases, severe thrombo-embolic complications have been observed at the very beginning of the disease; however no further complication has been seen, when the patients were actively treated (phlebotomies or 32P); at the present time, no one of these cases did show transformation into acute leukemia, but the long-term prognosis (beyond 15 years) cannot yet been precisely drawn.

Topics: Adolescent; Adult; Bloodletting; Erythrocyte Volume; Female; Follow-Up Studies; Hemoglobinometry; Hemoglobinopathies; Humans; Male; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Thromboembolism

A survey is given on the modern possibilities of the therapy of malignant tumours with radiopharmaca. In detail the following methods of treatment introduced into the nuclearmedical therapy are described: 1. Radioiodine therapy in folliculary and papillary carcinomas of the thyroid gland, 2. Radiophosphorus therapy in polycythaemia vera and myeloproliferative syndrome, 3. Radiogold therapy in peritoneal and pleural carcinoses, 4. Intrathecal radionuclide application in meningeosis leucaemica, 5. Intralymphatic radionuclide application to the therapy of malignant lymphomas, 6. Radionuclide therapy of multiple bone metastases. With the help of literature and own experiences the author enters the indication and the performance of the therapy as well as the possible successes of treatment, when using the therapy forms mentioned.

Topics: Aged; Gold Radioisotopes; Humans; Injections, Spinal; Iodine Radioisotopes; Male; Neoplasms; Phosphorus Radioisotopes; Pleural Neoplasms; Polycythemia Vera; Radioisotopes; Thyroid Neoplasms

Topics: Busulfan; Humans; Phosphorus Radioisotopes; Polycythemia Vera

The data of 140 patients with polycythemia vera during the period 1955--1975 were analyzed with regard to clinical signs and prognosis. The average age was 53,4 years. The sex ratio was 1.9:1 in favor of men. The most frequent symptoms were headache and vertigo. In more than half of the cases hepatosplenomegaly and hypertension were found. Besides typical changes in the blood count with elevated erythrocytes, hemoglobin, hematocrit, leukocytes and thrombocytes, increased levels of alkaline leukocyte phosphatase and uric acid were found. As to therapy, after 32P-medication the survival was two years longer than after phlebotomy. In 9 patients osteomyelofibrosis developed, and in 7 cases chronic myeloic leukemia. The mean age of death was 61 years.

Topics: Adolescent; Adult; Aged; Bloodletting; Cardiovascular Diseases; Female; Hematopoiesis; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis

Systemic mastocytosis occurred as a fatal event in a patient with long-standing polycythemia vera. The patient had been treated over the course of 21 yr with radioactive phosphorus. Possible relationships between mastocytosis and polycythemia vera, and also between mastocytosis and treatment with ionizing radiation, are discussed. Histopathologic and electron microscopic findings are illustrated. Difficulties in establishing the diagnosis of mast cell disease in this setting are also described.

Topics: Biopsy; Gastrointestinal Hemorrhage; Humans; Liver; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Postoperative Complications; Psoriasis; Splenectomy; Splenomegaly; Urticaria Pigmentosa

The various myeloproliferative diseases have different symptoms, therapeutic problems, and prognoses. The most common of these disorders appears to be agnogenic myeloid metaplasia, which primarily affects older persons. The five-year survival rate at the Mayo Clinic for these patients is 58%, and the prognosis depends on the presence of symptoms, anemia, and thrombocytopenia and on the size of the liver. Androgen therapy is often necessary to control anemia, and splenectomy may be indicated.

Topics: Adult; Aged; Chlorambucil; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Erythrocyte Aging; Humans; Isoflurophate; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Cell Count; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis; Splenomegaly; Time Factors

This review covers the side effects and adverse reactions to radiopharmaceuticals that were reported in the literature over the past 25 years. The information published prior to 1970 is sporadic, but due to the increased utilization of nuclear medicine procedures and the recognition that radiopharmaceuticals may have pharmacologic side effects, a registry has existed since 1971 to tabulate information on such effects. This survey is medical, rather than pharmaceutical in emphasis and so the adverse reactions are classified according to the target-organ systems involved rather than according to the specific radionuclides or to pharmaceuticals. If any of the radiopharmaceuticals of present or past use are not mentioned in this review, it is because no reports on their side effects were retrived by us. Hopefully, the organized registry system suggested by the Society of Nuclear Medicine (SNM) will enable a more complete recording of side effects from radiopharmaceuticals in the future.

Topics: Bone Marrow; Brain Diseases; Colloids; Gold Colloid, Radioactive; Humans; Hyperthyroidism; Iodine Radioisotopes; Iron; Kidney Diseases; Liver Diseases; Lung Diseases; Meningitis; Peritoneum; Phosphorus Radioisotopes; Polycythemia Vera; Pyrogens; Radioisotopes; Radionuclide Imaging; Radiotherapy; Registries; Serum Albumin; Serum Albumin, Radio-Iodinated; Skin; United States; Xenon Radioisotopes

The composition of the hemopoiesis was determined in iliac crest biopsies of 51 patients with polycythaemia vera. There was a good correlation between thrombopoiesis and thrombocytes and, to a minor degree also between erythropoiesis and erythrocytes in untreated patients as well as between granulopoiesis and granulocytes in 32P-treated patients. In patients with normal blood counts there existed no correlation between the bone marrow and the blood counts within smaller limits of the cell count. Histomorphometric analysis shows no difference either between untreated and 32P-treated patients or between patients with and without splenomegaly. This is an argument against a significant intrasplenic hemopoiesis or an intrasplenic cell pooling, or destruction (hypersplenism), respectively. The blood sinusoids are hyperplastic and distended. With increasing hyperplasia of the hemopoiesis the sinusoids become relatively smaller. So changes in vascularisation may be of importance in the infrequent transitions into myelofibrosis and/or leukemia.

Topics: Biopsy; Blood Cell Count; Blood Platelets; Blood Vessels; Bone Marrow Examination; Erythrocyte Count; Erythropoiesis; Granulocytes; Hematopoiesis; Humans; Hyperplasia; Hypersplenism; Ilium; Phosphorus Radioisotopes; Polycythemia Vera; Splenomegaly

Topics: Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotope Teletherapy; Radiotherapy Dosage

Topics: Female; Glycoproteins; Humans; Lipoproteins; Male; Phosphorus Radioisotopes; Polycythemia Vera

A 74-year-old white man with established polycythemia vera was treated with radioactive phosphorus after phlebotomies alone failed to control his disease. About 2 3/4 years later he died of multiple myeloma. The mutagenic effect of radioactive phosphorus may have caused or possibly accelerated preexisting myeloma. Basic nonmalignant disease deserves careful consideration before radiation or radiomimetic agents are used. One might consider a probably less mutagenic drug such as hydroxyurea in patients with polycythemia vera when phlebotomy alone does not give good control of red cell mass and thrombocytosis.

Topics: Aged; Humans; Male; Multiple Myeloma; Neoplasms, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Transfusion; Bloodletting; Bone Marrow; Bone Marrow Cells; Chlorambucil; Chronic Disease; Erythrocytes; Erythropoietin; Female; Humans; Leukemia; Liver; Male; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Spleen; United States

The onset of postpolycythemic myeoloid metaplasia or spent polycythemia has been recognized for many years. As the result of many different series, the development of postpolycythemic myeolid metaplasia might be expected in from 15%-20% of patients with postpolycythemia vera. It appears that an etiologic role for sodium phosphate 32P may exist in this evolutionary pattern. About 70% of patients with PPMM will have symptoms with the onset of the syndrome. The major mechanisms producing symptoms result from (1) anemia, (2) pressure from massive splenomegaly, and (3) bleeding problems. Iron deficiency is a frequent cause of anemia in patients with PPMM. The major mechanism of anemia in these patients, however, relates to ineffective erythropoiesis and shortened red cell survival. Androgen trials for ineffective erythropoiesis seem worthwhile, although data on this point is too limited to draw any firm conclusions. A steroid trial for those patients with major hemolytic episodes is indicated. In those patients in whom adrenal steroid therapy fails to control major hemolysis, a consideration for splenectomy exists. Pressure-related manifestations secondary to massive splenomegaly have been treated with radiation therapy and oral alkylators. Although there is data to document amelioration of painful symptoms with associated shrinking of the spleen, long-term control of this problem has not been forthcoming. Again, patients who are medical failures in control of pressure-related manifestations may be considered for splenectomy. Bleeding problems may arise with PPMM secondary to thrombocytopenia, thrombocythemia, or qualitative platelet dysfunction. Adrenal steroids have met with some success in improving platelet counts in patients with life-threatening thrombocytopenia. Those patients who are medical failures with adrenal steroids in terms of thrombocytopenia might be candidates for splenectomy. Control of thrombocythemia has been observed with oral alkylator therapy and chlorambucil may have a special role in managing this complication. Qualitative platelet defects leading to severe bleeding are best managed with fresh platelet transfusions. Patients with PPMM in contrast to patients with agnogenic myeoloid metaplasia have a more lethal syndrome and shortened survivorship. Causes of death in patients with PPMM include cardiac problems, transition to acute leukemia, hemorrhage, and infection.

Topics: Anemia; Female; Humans; Iron; Male; Phosphorus Radioisotopes; Polycythemia Vera; Prednisone; Primary Myelofibrosis; Splenomegaly

Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes.

Topics: Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy Dosage

Experience with cytostatic treatment performed in patients with polycythaemia rubra vera is reviewed. The effectivity and side effects of the drugs applied are evaluated. Mannosulfan and mitobromitol were the drugs most sutiable for treatment. In certain special cases, 5-hydroxyurea was also satisfactory, while mitolactol was the least suitable.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Hydroxyurea; Male; Mesylates; Middle Aged; Mitobronitol; Phosphorus Radioisotopes; Polycythemia Vera; Remission, Spontaneous

A group of 52 consecutive patients with polycythemia vera was submitted to long-term therapy with radioactive phosphorus (32P). Initial phase of therapy induced complete remissions (normalization of hematogram; spleen not palpable) in 45% of the patients, and partial remissions in the remaining 55%. During maintenance therapy of the complete remission group, mean remission time was about 3.5 years. Individual remission times ranged between 1 and 6 years. In the group of patients with incomplete remission, mean remission time increased with the progression of the disease due to gradual development of "spent" -polycythemia. In patients with splenomegaly, remission time was negatively correlated to spleen size. In both groups the increment of annual accumulated dose averaged 2.4 mCi 32P. When considering polycythemia related causes of death only, mean survival time attained 12 years after initial treatment with 32P. Acute leukemia occurred in 2 patients (4%).

Topics: Adult; Aged; Alkylating Agents; Female; Follow-Up Studies; Humans; Leukemia; Long-Term Care; Male; Middle Aged; Palpation; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Radiotherapy Dosage; Splenomegaly; Time Factors

Topics: Aged; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

Chronic granulocytic leukemia developed in a 59-year-old woman who had previously received a total of 21 mCi -32P for polycythemia vera. She was treated with Myleran (busulphan) for her chronic granulocytic leukemia. Cytogenic studied revealed deletion of chromosomes No. 8 and 12, and translocation between 1 and 8. The patient also developed a severe antoimmune hemolytic anemia, for which she received prednisone treatment. She died with a perforated stomach ulcer.

Topics: Anemia, Hemolytic, Autoimmune; Busulfan; Chromosomes, Human, 1-3; Chromosomes, Human, 6-12 and X; Chronic Disease; Female; Humans; Karyotyping; Leukemia, Myeloid; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Prednisone; Translocation, Genetic

Polycythemia rubra vera and chronic myelogenous leukemia are both myeloproliferative disorders and, as such, share certain clinical features. Although some myeloproliferative disorders may transform into others, conversion of polycythemia rubra vera to chronic myelogenous leukemia has been denied. We report here an elderly man with polycythemia rubra vera and a normal leukocyte alkaline phosphatase who developed chronic myelogenous leukemia with a low leukocyte alkaline phosphatase and a marrow karyotype of 45, X, Ph1-positive. In addition, we have collected evidence of two similar cases and thus conclude that, although uncommon, polycythemia rubra vera may on occasion progress to chronic myelogenous leukemia.

Topics: Adult; Aged; Chromosome Aberrations; Chromosomes, Human, 21-22 and Y; Female; Humans; Karyotyping; Leukemia, Myeloid; Male; Middle Aged; Neoplasms, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera

A review is presented of the clinical, physiopathological and therapeutic aspects of four varieties of chronic myeloproliferative syndrome: polycythemia vera, idiopathic thrombocythemia, chronic myelocytic leukemia and idiopathic myeloid metaplasia. Routine and experimental therapeutic approaches are discussed.

Topics: Aged; Bloodletting; Busulfan; Chlorambucil; Female; Humans; Leukemia, Myeloid; Male; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Remission, Spontaneous; Thrombocytosis

Radionuclide studies of the erythron are valuable to the physician in evaluating the clinical situation in a wide variety of hematologic disorders. A complete and accurate analysis of the life cycle of the red cell can be obtained with a full iron kinetic study, in conjunction with a DF32P red-cell survival study. However, a complete iron kinetic study is not always necessary. It may be abbreviated by deleting the in vitro phase of the iron kinetic procedure. The abbreviated iron kinetic study is also done in conjunction with a DF32P red-cell survival study. It can easily be performed by injecting 59Fe-labeled plasma and monitoring externally over the spleen, liver, and sacrum. Measurements of red-cell survival may be obtained with either 51Cr or DF32P. Although 51Cr provides a relatively uniform label of circulating red cells and is convenient to count in vitro, its highly variable elution rate precludes an accurate measurement of erythrocyte survival. The 51Cr method provides only a rough index of circulating red-cell half-times as a measure of red-cell survival. DF32P, HOWEVER, IS A PERMANENT LABEL OF CIRCULATING RED CELLS. It provides a direct measurement of erythrocyte survival and permits in vivo labeling of red cells simply by means of direct intravenous injection. Because it has an elution rate that is virtually zero after minimal elution on the day of injection, and because it is not reutilized, DF32P is unquestionably the best agent known for the determination of red-cell survival. In addition to these diagnostic data, the complete iron kinetic study can provide data on the deposition of iron in storage and the rate of iron storage exchange. It can also determine if erythropoiesis is quantitatively abnormal and if the abnormality is located in the bone marrow or in other organs such as the liver or spleen. Although the study of hematologic disorders is one of the most rapidly developing areas of medical research, techniques that are currently available can provide an understanding of the life cycle of the red cell and valuable data that can be applied directly to the clinical situation. When performed accurately, these studies provide a thorough analysis of the pathophysiology of the erythron and are valuable clinical tools that can be used successfully in the diagnosis and evaluation of a broad spectrum of hematological disorders.

Topics: Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Hypochromic; Anemia, Pernicious; Bone Marrow Diseases; Cell Survival; Chromium Radioisotopes; Erythrocytes; Hemochromatosis; Hemoglobinuria, Paroxysmal; Hemosiderosis; Humans; Iron Radioisotopes; Isoflurophate; Isotope Labeling; Leukemia; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radioisotopes; Radionuclide Imaging; Spherocytosis, Hereditary; Splenic Diseases; Vitamin E Deficiency

Retrospective studies were carried out in 52 patients with polycythemia vera who were treated with radioactive phosphorus (32-P) over periods ranging between 4 and 24 years. Control of hematopoiesis was achieved in all patients. Duration of the remission induced differed considerably in the individual patients. Mean remission lasted 3-4 years. After 13 years of 32-P treatment, the mean duration of remission lengthened due to gradual transition of some cases into "spent" polycythemia. The mean annual dose of 32-P was about 2.4 mCi. In patients with long-term remissions, the dose accumulated per year was markedly less. These patients probably represent optimal preconditions for 32-P therapy. Mean survival was 12.5 years. The majority of the patients died from thorombo-embolie events or hemorrhage; incidence of acute leukemia was about 4%.

Topics: Acute Disease; Adult; Aged; Female; Hemorrhage; Humans; Leukemia; Male; Methods; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy Dosage; Remission, Spontaneous; Splenomegaly; Thromboembolism; Time Factors

Incorporation of [32P]-orthophosphate into plasma phospholipids was investigated in 11 patients with polycythemia vera. The specific activity of phospholipid radioactive precursors (TCA-extract) was maximal 1 hour after the delivery of radioactive phosphorus and dropped to less than 20 per cent of maximal value after 24 hours. The peak of total phospholipid specific activity was observed 48 hours after the administration of [32P]-orthophosphate in 10 patients, and after 24 hours in one, and decreases regularly afterward. The half-life of the lipid-bound phosphorus in the plasma of investigated patients, determined during the decrease of their specific activity was 252+/-60 hours. Concentration of total plasma phospholipids and the pattern of individual phospholipid found in patients with polycythemia vera were similar to those reported for normal individuals. The rate of incorporation of the labeled phosphorus into phosphatidylethanolamine and phosphatidic acid was much more rapid than into lysophosphatidylcholine, sphingomyelin, or phosphatidylcholine.

Topics: Chromatography, Thin Layer; Female; Half-Life; Humans; Liver; Male; Phosphates; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Phosphorus Radioisotopes; Polycythemia Vera; Sphingomyelins; Time Factors

Three hundred and three cases of polycythaemia vera were treated between 1949 and 1961 using radioactive phosphorus, the minimum follow-up for the patients in the group being 12 years and the maximum 24 years. Two hundred and thirty three patients died, the median duration of survival after the first treatment with phosphorus being 10 years (i.e. 12 years after the diagnosis was made). 59 patients died of the vascular complications of polycythaemia, 76 of leukaemia or myelofibrosis. The total number of deaths due to vascular complications up to the tenth year exceeded the total number of deaths due to haematological complications (leukaemia or myeloid metaplasia). At the end of the 11th year the opposite was true. From the ninth year onwards, acute leukaemia and myelofibrosis represent more than 40 p.cent of deaths of known cause and the annual probability of death from a haematological cause for the surviving patients increases regularly until the fifteenth year when it reaches approximately 5 p.cent of the patients at risk. However the median survival of patients dying from acute leukaemia or myeloid splenomegaly is slightly longer than that of patients dying from other causes, this confirming that these disorders would appear to represent the terminal phase in the course of polycythaemia vera.

Topics: Acute Disease; Aged; Female; Follow-Up Studies; Hemorrhage; Humans; Kidney Neoplasms; Leukemia; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Splenomegaly; Thrombosis

The aim of this study is to assess the present status of 32P-therapy in the management of polycythemia vera. The nature of the disease and its associated clinical problems was considered with respect to the characteristics of the different therapeutic approaches. We concluded that 32P is preferably administered to older patients, especially if long term remissions are achieved, if drugs are taken unreliably, or if patients are difficult to supervise. At present chemotherapy is preferably administered to younger patients, to those who respond inadequately to 32P, or who demonstrate early relapsing hyperproliferation of granulocytopoiesis, or who require 32P-administration at intervals shorter than one year.

Topics: Alkylating Agents; Blood Platelets; Bloodletting; Cytarabine; Granulocytes; Hematopoiesis; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Pyrimidines

Topics: Humans; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Adult; Aged; Female; Humans; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Radiotherapy Dosage

Topics: Adult; Aged; Alkaline Phosphatase; Blood Platelets; Blood Volume; Bone Marrow; Chlorambucil; Erythrocyte Count; Erythropoietin; Female; Hemoglobins, Abnormal; Hookworm Infections; Humans; Hydrogen-Ion Concentration; Leukocyte Count; Male; Middle Aged; Oxygen; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Pruritus; Riboflavin Deficiency; Uric Acid; Vitamin B 12

Topics: Adrenal Cortex Hormones; Androgens; Blood Transfusion; Bloodletting; Busulfan; Chlorambucil; Cyclophosphamide; Humans; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Spleen; Splenectomy; Thrombocytosis

Topics: Bloodletting; Humans; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Busulfan; Chronic Disease; Diagnosis, Differential; Hemorrhage; Humans; Phosphorus Radioisotopes; Polycythemia Vera; Thrombosis

Topics: Female; Follow-Up Studies; Humans; Male; Phosphorus Radioisotopes; Polycythemia Vera; Remission, Spontaneous

Topics: Aged; Blood Platelets; Blood Transfusion, Autologous; Bloodletting; Busulfan; Erythrocyte Count; Female; Hematocrit; Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer; Phosphorus Radioisotopes; Polycythemia Vera; Postoperative Complications; Surgical Procedures, Operative; Thrombosis

Topics: Autopsy; Blood Platelets; Blood Sedimentation; Hemoglobins; Humans; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Time Factors

Topics: Acute Disease; Bloodletting; Female; Hemorrhage; Humans; Leukemia; Male; Middle Aged; Minnesota; Phosphorus Radioisotopes; Polycythemia Vera; Pressure; Primary Myelofibrosis; Retrospective Studies; Sex Factors; Splenectomy; Splenomegaly; Syndrome

Topics: Adult; Aged; Female; Heart; Humans; Lung; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radiography; Remission, Spontaneous

Topics: Blood Cell Count; Blood Platelets; Erythrocytes; Humans; Leukocytes; Leukocytosis; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis; Reticulocytes; Splenomegaly

Topics: Busulfan; Female; Humans; Japan; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis

Topics: Alkylating Agents; Humans; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Volume; Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Volume; Bloodletting; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Administration, Oral; Bone Marrow; Bone Marrow Cells; Erythrocytes; Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radioactivity

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Isotopes; Phosphorus; Phosphorus Isotopes; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Coagulation Factors; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Blood Volume; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity; Water-Electrolyte Imbalance

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Long-Term Care; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity; Radioisotopes

Topics: Hematologic Diseases; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Internal Medicine; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Electrocardiography; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Incidence; Leukemia; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Hodgkin Disease; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Peripheral Vascular Diseases; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Vascular Diseases

Topics: Humans; Mouth; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Leukocytes; Minnesota; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis; Research

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Biochemical Phenomena; Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Bone and Bones; Bone Neoplasms; Hodgkin Disease; Humans; Leukemia; Multiple Myeloma; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Plasma Cells; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Hodgkin Disease; Humans; Leukemia; Lymphoma; Multiple Myeloma; Phosphorus; Phosphorus Radioisotopes; Plasma Cells; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Hemostatics; Leukemia; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Prothrombin; X-Ray Therapy; X-Rays

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Iron; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Disease Management; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Blood Platelets; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Blood Coagulation; Factor V; Factor V Deficiency; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Blood; Body Fluids; Humans; Injections; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Plasma; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Hematology; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Disease; Hematopoietic System; Humans; Leukemia; Minnesota; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Blood Coagulation; Gold Radioisotopes; Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes

Topics: Chorea; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Hemoglobins; Humans; Oxygen; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Disease Management; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity; Weapons

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Iron; Iron Compounds; Iron Metabolism Disorders; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Bone Marrow; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Gout; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Anemia; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Disease; Humans; Iodine; Iodine Radioisotopes; Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity; Thyroid Diseases; Thyroid Gland

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Dental Care; Follow-Up Studies; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Bone Marrow; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Bone Marrow; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity

Topics: Leukemia; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Phosphorus; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera

Topics: Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia; Polycythemia Vera; Radioactivity