phosphorus-radioisotopes and Agranulocytosis

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

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

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anemia, Aplastic; Blood Transfusion; Bone Marrow Cells; Bone Marrow Examination; Cell Movement; Female; Granulocytes; Humans; Isoflurophate; Leukocyte Count; Leukocytes; Male; Middle Aged; Neutropenia; Phosphorus Radioisotopes

Topics: Adult; Aged; Agranulocytosis; Arthritis, Rheumatoid; Blood Volume; Cell Survival; Felty Syndrome; Female; Half-Life; Humans; Isoflurophate; Leukocyte Count; Male; Middle Aged; Muramidase; Neutropenia; Phosphorus Radioisotopes; Splenectomy

Leukocyte kinetic studies were performed by labelling neutrophilic leukocytes in vivo with radioactive diisopropylfluorophosphate and measuring the time taken for the label to traverse the myelocyte compartment, marrow granulocyte reservoir and blood (myelocyte-to-tissue transit time). Leukocyte specific activity (LSA) reached background levels within 17 to 22 days in normal subjects and more rapidly than normal in patients with neutropenia due to hypersplenism or marrow aplasia. When neutropenia was partially or completely corrected by splenectomy the label disappeared more slowly. In patients with stable neutrophilia the label disappeared slowly and a terminal plateau in the LSA curve was encountered. Analysis of LSA curves suggests that disappearance of labelled neutrophil cohorts is influenced by circulating neutrophil levels, not only by an effect on release of cells from the marrow granulocyte reservoir but also, directly or indirectly, by an effect on myelocyte proliferation.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Biological Transport; Child; Female; Humans; Hypersplenism; Isoflurophate; Leukocyte Count; Leukocytes; Male; Middle Aged; Myeloproliferative Disorders; Neutropenia; Neutrophils; Phosphorus Radioisotopes; Splenectomy; Time Factors

Topics: Agranulocytosis; Cell Division; DNA Replication; Humans; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid; Neutrophils; Phosphorus Radioisotopes

Human cyclic neutropenia is characterized by severe depression of blood neutrophil levels approximately every 21 days. To investigate the mechanism of cyclic neutropenia four patients were studied with daily complete blood counts, serial bone marrow examinations, marrow reserve testing, serum muramidase determinations, DF(22)P granulocytokinetic studies, and, in one patient, in vivo [(3)H]TdR labeling. Periodogram analysis of the serial blood counts in the latter patient and visual inspection of multiple cycles in the others revealed periodic fluctuations in the levels of blood neutrophils, monocytes, lymphocytes, reticulocytes, and platelets. Rhythmic changes in the morphologic and radioisotopic studies as well as the marrow reserve tests and muramidase measurements were consonant with a mechanism of periodic failure of marrow production rather than peripheral destruction. Human cyclic neutropenia is analogous to cyclic neutropenia in the grey collie dog and may be viewed as the consequence of cyclic hematopoiesis.

Topics: Agranulocytosis; Animals; Blood Cell Count; Blood Platelets; Bone Marrow Examination; Dogs; Erythrocyte Count; Hematopoiesis; Humans; Isoflurophate; Leukocyte Count; Muramidase; Periodicity; Phosphorus Radioisotopes; Thymidine; Tritium

Topics: Agranulocytosis; Blood Flow Velocity; Bronchopulmonary Sequestration; Cell Survival; Humans; Isoflurophate; Kinetics; Leukocyte Count; Neutropenia; Phosphorus Radioisotopes; Renal Dialysis; Time Factors