phosphorus-radioisotopes and Leukemia

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

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: 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

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

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

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

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 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

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

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

Topics: Adolescent; Autoimmune Diseases; Child; Hemarthrosis; Hemophilia A; Humans; Inflammation; Leukemia; Male; Osteoarthritis; Phosphorus Radioisotopes; Radiopharmaceuticals; Synovial Membrane

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

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Busulfan; Fatal Outcome; Female; Humans; Hydroxyurea; Leukemia; Male; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Phosphorus Radioisotopes; Pipobroman; Thrombocythemia, Essential

We have investigated thrombin-stimulated morphological changes and the activation of phosphoinositide 3-kinase (PI 3-K), as manifested by the accumulation of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 (labelled with 32P or myo-[3H]inositol), in CHRF-288 cells, a leukaemic cell line derived from a platelet progenitor cell. We report that these cells, when exposed to thrombin or SFLLRN (the peptide Ser-Phe-Leu-Leu-Arg-Asn, a thrombin-receptor ligand) rapidly change shape, forming membrane 'blebs', detectable by differential interference contrast or confocal microscopy, as well as labelled 3-phosphorylated phosphoinositides. The 'blebs' are distinguishable from 'ruffles' or lamellae, since they do not contain phalloidin-detectable actin. Studies with permeabilized cells indicate that PI 3-K is activated synergistically by thrombin+guanosine 5'[gamma-thio]triphosphate. Two forms of PI 3-K, i.e. PI 3-K(gamma) and p85/PI 3-K, regulated by G beta gamma subunits of heterotrimeric G-protein and the small G-protein Rho, respectively, are present in these cells, as is true for platelets. Wortmannin, a known potent and specific inhibitor of PI 3-K activities, inhibits thrombin-stiumlated accumulation of 3-phosphorylated phosphoinositides in a dose-dependent manner (IC50 approximately 10nM), without affecting phospholipase C activation. Pretreatment of CHRF-288 cells with either wortmannin (100 nM) or an unrelated synthetic PI 3-K inhibitor, LY294002 (50 microM), abolishes thrombin-receptor-stimulated blebbing. These results suggest that thrombin-stimulated accumulation of 3-phosphorylated phosphoinositide(s) is required for the shape-change response in CHRF-288 cells.

Topics: Androstadienes; Blood Platelets; Blotting, Western; Cell Membrane; Cell Membrane Permeability; Enzyme Inhibitors; Humans; Isoenzymes; Kinetics; Leukemia; Peptide Fragments; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Phosphorus Radioisotopes; Phosphotransferases (Alcohol Group Acceptor); Receptors, Thrombin; Thrombin; Tumor Cells, Cultured; Wortmannin

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

The reported higher efficiency of UTP, relative to ATP, as phosphate donor for deoxycytidine kinase (dCK), has been extended and found to apply to both dCyd and dAdo as acceptors. UTP as phosphate donor was shown to follow strictly Michaelis kinetics, with Km = 1 microM, in striking contrast to ATP, which exhibits marked negative cooperativity (Hill coef. = 0.7) with a several-fold higher Kmapp = 15 microM. Phosphate transfer was followed directly with use of mixtures of [gamma-32P]ATP and cold UTP as donors, or with 3H-labeled acceptors and cold donors. With equimolar concentrations of ATP and UTP (50 microM or 1 mM each), and dCyd or dAdo as acceptor, only minimal phosphate transfer occurred from ATP (3-10%). With a 6:1 ratio of ATP:UTP, hence exceeding the intracellular ratio, phosphate transfer from ATP increased, but still did not exceed 25-40% with either dCyd or dAdo as acceptor. Moreover, relative ATP transfer is dependent on the dCyd concentration. We conclude that the major intracellular phosphate donor for dCK is not ATP, but UTP. Preliminary data for human thymidine kinases (TK1 and TK2) exhibit quite different behaviour. The foregoing, together with literature data, are highly relevant to in vitro studies on the properties of the nucleoside kinases, and to the design of chemotherapeutically active nucleoside analogues.

Topics: Adenosine Triphosphate; Deoxyadenosines; Deoxycytidine; Deoxycytidine Kinase; Humans; Kinetics; Leukemia; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Spleen; Substrate Specificity; Tritium; Uridine Triphosphate

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

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

The biosynthetic and structural characteristics of the human thymocyte/T cell antigen defined by the monoclonal antibody WT1 have been studied. WT1 identified a monomeric cell surface glycoprotein of Mr = 40,000 ( gp40 ). Cross-absorption experiments and two-dimensional gel analyses indicate that WT1 and another monoclonal antibody, 3A1, react with the same structure. This glycoprotein was asymmetrically inserted into the rough endoplasmic reticulum as a transmembrane structure. At this stage, the polypeptide chain possessed two N-linked, "high-mannose" type glycans; these were subsequently processed into endo-H-insensitive, complex oligosaccharides during intracellular transport to the cell surface. Inhibition of N-linked glycosylation with tunicamycin failed to block the processing of the nonglycosylated Mr = 29,000 polypeptide to a glycoprotein of Mr = 33,000. Cleavage of the mature Mr = 40,000 form with endo-F yielded a similar Mr = 33,000 product. The kinetics of synthesis of the Mr = 33,000 intermediate in conjunction with gal-NAc oligosaccharidase digestion indicated the presence of O-linked glycans in the mature cell surface WT1 antigen. The fully processed cell surface form of the polypeptide also contains covalently associated fatty acid, and was labeled by 32P phosphate, the predominantly labeled phosphoamino acid being phosphoserine. We also demonstrate biochemically that the reactivity of WT1 with cells from a few patients with acute myeloid leukemia reflects genuine expression of the gp40 structure on myeloid cells.

Topics: Adult; Antibodies, Monoclonal; Antigens, Surface; Glycoproteins; Humans; Leukemia; Microsomes; Molecular Weight; Palmitic Acid; Palmitic Acids; Phosphorus Radioisotopes; Polysaccharides; T-Lymphocytes; Tunicamycin

32P is effective therapy for polycythemia and primary thrombocytosis. The Polycythemia Vera Study Group is comparing radioactive phosphorus with alkylating agents to determine relative efficacy. Less well investigated is the effectiveness of 32P vs. busulfan in chronic granulocytic leukemia. Endolymphatic administration of radiopharmaceuticals may play a role in the therapy of infradiaphragmatic lymphoma. Among the radionuclides that have at times been used in hematology are 32P, 198Au 24Na, 76As, 89Sr, 52Mb, 54Mn, 91Y, 95Zr, 95Cb, 111Ag, 109Pd, 131I, 185W, and 192Ir. As stated, 32P has proven single most efficacious agent. The hematologic diseases that have been treated include both malignant and benign conditions. Among the malignant conditions are polycythemia vera, agnogenic myeloid metaplasia, thrombocythemia, leukemia, Hodgkin's disease, and multiple myeloma. Hemophilia, and Osler--Weber--Rendu disease are among the benign entities in which the agents have been tried. Polycythemia and thrombocythemia remain those in which the greatest success has been achieved.

Topics: Gold Radioisotopes; Hematologic Diseases; Humans; Leukemia; Myeloproliferative Disorders; Palladium; Phosphorus Radioisotopes; Radioisotopes; Tungsten

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

Leucocytes from normal donors and leukemia patients were isolated and lebelled in vitro with 32P-orthophosphate in order to compare labelling characteristics of nuclear high-molecular weight RNA, labelling characteristics, nucleotide compositions and oligonucleotide frequencies of ribosomal 28 S RNA. These studies revealed 1. structural microheterogeneity of 28 S RNA between the various leukemia cells studies without presenting a leukemia-specific structural marker, 2. an impaired production of ribosomal 28 S RNA from its nuclear precursor 45 S RNA in acute myeloblastic leukemia compared to PHA-stimulated normal lymphocytes. In the second part of this work, the influence of RNA from immunocompetent lymphocytes on the PHA-stimulation of M. Hodgkin lymphocytes was analyzed; the third part deals with studies on macromolecular carriers forcytostatic anthracyclines in human leukemia cells.

Topics: Hodgkin Disease; Humans; In Vitro Techniques; Isotope Labeling; Leukemia; Leukocytes; Macromolecular Substances; Phosphorus Radioisotopes; RNA, Neoplasm; RNA, Ribosomal

Topics: Blood; Child; Extracorporeal Circulation; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus Radioisotopes; Spleen; Thymus Gland

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

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

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

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

Topics: Acute Disease; Cell Nucleolus; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Lymphocytes; Lymphoma, Non-Hodgkin; Phosphorus Radioisotopes; RNA, Neoplasm; RNA, Ribosomal

Topics: Alkaline Phosphatase; Anemia, Aplastic; Blood Coagulation Tests; Bone Marrow Examination; Busulfan; Chromosome Aberrations; Female; Fibrinogen; Gastrointestinal Hemorrhage; Humans; Inclusion Bodies; Leukemia; Leukocytes; Male; Phosphorus Radioisotopes; Prothrombin Time; Thiotepa; Thrombocytosis

Topics: Base Sequence; Burkitt Lymphoma; Cell Line; Cells, Cultured; Centrifugation, Density Gradient; Chromatography, DEAE-Cellulose; Genes; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphocyte Activation; Lymphocytes; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Purines; Remission, Spontaneous; Ribonucleases; RNA, Ribosomal

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: Burkitt Lymphoma; Cell Division; Cell Nucleus; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukocytes; Lymphocyte Activation; Lymphocytes; Molecular Weight; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Proteins; Sodium Dodecyl Sulfate; Tritium

Topics: Burkitt Lymphoma; Cell Nucleus; Centrifugation, Density Gradient; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Phosphorus Radioisotopes; RNA, Neoplasm; Sucrose

Topics: Animals; Anura; Autoradiography; Biological Assay; Cells, Cultured; Centrifugation, Density Gradient; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Female; Globins; Leukemia; Neoplasms, Experimental; Ovary; Phosphorus Radioisotopes; Polyribosomes; Protein Biosynthesis; RNA, Messenger; RNA, Ribosomal; RNA, Transfer; Spleen; Templates, Genetic

Topics: Humans; Leukemia; Lymphoma; Molecular Conformation; Phosphorus Radioisotopes; RNA, Neoplasm

Topics: Chlorambucil; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Lymphocytes; Mechlorethamine; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes

Topics: Chronic Disease; Humans; Leukemia; Leukocytes; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Radiation-Induced; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Chronic Disease; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; X-Ray Therapy

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

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

Topics: Granulocytes; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Phosphorus; Phosphorus Radioisotopes

Topics: Chronic Disease; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

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

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

Topics: Adrenocorticotropic Hormone; Cortisone; Leukemia; Lymphoma; Mechlorethamine; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes; Radiotherapy; Spleen; Steroids; Urethane; X-Rays

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

Topics: Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Radiotherapy; X-Ray Therapy

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

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

Topics: Blood Cells; DNA; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Acute Disease; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radiotherapy; X-Ray Therapy

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

Topics: Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Phosphorus; Phosphorus Radioisotopes; Sex Characteristics

Topics: Chronic Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Radioactivity

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

Topics: Chronic Disease; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes; Radiotherapy; Whole-Body Irradiation; X-Rays

Topics: Chronic Disease; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

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

Topics: Chromium Compounds; Humans; Leukemia; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

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

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

Topics: Adrenocorticotropic Hormone; Cortisone; Folic Acid Antagonists; Humans; Leukemia; Lymphoma; Mechlorethamine; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Triethylenemelamine; Urethane

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

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

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

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

Topics: Leukemia; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

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

Topics: Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

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

Topics: Leukemia; Lymphoma; Mechlorethamine; Nitrogen Mustard Compounds; Peptide Nucleic Acids; Phosphorus; Phosphorus Radioisotopes; Urethane

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

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

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes

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

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

Topics: Humans; Leukemia; Leukemia, Lymphoid; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Skin

Topics: Leukemia; Leukemia, Lymphoid; Lymphatic Vessels; Phosphorus; Phosphorus Radioisotopes

Topics: Blood; Half-Life; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Half-Life; Leukemia; Phosphorus; Phosphorus Radioisotopes; Plasma

Topics: Erythrocytes; Half-Life; Humans; Leukemia; Phosphorus; Phosphorus Radioisotopes

Topics: Half-Life; Humans; Leukemia; Leukocytes; Phosphorus; Phosphorus Radioisotopes; Plasma