Evaluación del riesgo radiológico en la radiosinoviortesis y el tratamiento mielosupresor de la policitemia vera / Radiological risk assessment in radiosynoviorthesis and the myelosupressor treatment of polycythemia vera

Introducción: La aplicación del método de la matriz de riesgo para la evaluación del riesgo radiológico en la medicina permite identificar de manera proactiva debilidades en las etapas del proceso y hacer un plan de acciones de mejora para la seguridad y calidad. Objetivo: Evaluar los riesgos radiológicos de la radiosinoviortesis y el tratamiento mielosupresor con Fósforo-32 de la policitemia vera. Método: Se utilizó el método de matriz de riesgo y se realizó el análisis y tratamiento de los riesgos radiológicos por medio del código cubano SECURE-MR-FMEA 3.0. Resultados: El 17 por ciento del riesgo alto se eliminó con las medidas adicionales adoptadas; predominaron las consecuencias medias para los trabajadores y el público, 30 por ciento y el 14 por ciento, respectivamente. Las defensas más importantes fueron: levantamiento radiológico inicial de las áreas del departamento; revisión independiente del proyecto con las regulaciones de seguridad aplicables; inspección de trabajos de construcción civil y montaje de equipos antes de iniciar la operación del departamento; capacitación de los médicos nucleares en los tratamientos; existencia de protocolos de tratamiento; análisis de lecciones aprendidas de incidentes radiológicos; levantamiento radiológico periódico de las áreas del servicio y procedimiento de emergencia para reducir la dosis en órganos críticos en caso de administración errónea de radiofármacos. Se creó una base de datos de incidentes utilizada como referencia para el modelo utilizado. El factor humano fue la causa mayor de los sucesos radiológicos analizados (88 por ciento). Conclusiones: Estos resultados facilitan la toma de decisiones para el mejor desempeño de la radiosinoviortesis y el tratamiento de la policitemia vera con Fósforo-32 en Cuba. Se sugiere elaborar el plan de mejora de la seguridad con especial atención a las operaciones de administración del radiofármaco en ambos casos.(AU)

Introduction: The application of risk matrix for ionizing radiation medicine allow identify in proactive way the weakness of the process' step, which implies in the design of safety and quality improvement plan for this. Method: Risk matrix method applied for radiosynoviorthesis and the myelosupressor treatment with Phosphorus-32 of polycythemia vera. The Cuban code SECURE-MR-FMEA 3.0 is used. Results: It was eliminated the 17 percent of the high risk with additional measures, and the medium consequences for workers and public are 30 percent and 14 percent, respectively. The most important identified safety measures were the initial radiological monitoring from different nuclear medicine department areas; the project revision based on the applicable safety regulations; a survey of civil construction works and equipment assembly before work began; training of nuclear medicine doctors in related aspects of nuclear medicine treatments; existence of treatment protocols; the analysis of learned lessons from radiological incidents; the periodical radiological monitoring from different services areas and the emergency procedure for the cases of mistake in the radiopharmaceuticals administration. Human factor was the major cause in analyzed radiological events (88 percent). Conclusions: These results facilitate taking decisions for the best performance of radiosynoviorthesis and the myelosupressor treatment with Phosphorus-32 of polycythemia vera in Cuba. It is recommended to elaborate the safety improvement plan from these and focussing in the radiopharmaceutical administration operations in both cases.(AU)

ACR-ASTRO practice guideline for the performance of therapy with unsealed radiopharmaceutical sources.

This guideline is intended to guide appropriately trained and licensed physicians performing therapy with unsealed radiopharmaceutical sources. Adherence to this guideline should help to maximize the efficacious use of these procedures, maintain safe conditions, and ensure compliance with applicable regulations. The topics dealt with in this guideline include indications for the use of iodine-131, both for the treatment of hyperthyroidism and thyroid carcinoma. In addition, indications for other less common procedures include those for the use of phosphorous-32 in its liquid and colloidal forms, strontium-89, samarium-153, and the use of Y-90 antibodies.

A review of the therapeutic agents used in the management of polycythaemia vera.

The acquired clonal disorder Polycythaemia Vera leads to increased erythropoiesis, myelopoiesis and megakaryopoeisis. These anomalies result in an increased incidence of thromboembolic events, transformation to acute leukaemia and myelofibrosis. Treatments which aim to reduce the event rate may increase anaemia but may also affect the rate of complications. This paper reviews the evidence for the treatments which have been used in the management of the disorders over a 50 plus year period. Assessment of this evidence and its limitations form the basis for the current suggested management plans.

Hydroxyurea: The drug of choice for polycythemia vera and essential thrombocythemia.

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.

Release of patients after therapy with unsealed radionuclides.

After some therapeutic nuclear medicine procedures with unsealed radionuclides, precautions may be needed to limit doses to other people, but this is rarely the case after diagnostic procedures. Iodine-131 results in the largest dose to medical staff, the public caregivers, and relatives. Other radionuclides used in therapy are usually simple beta emitters (e.g. phosphorus-32, strontium-89, and yttrium-90) that pose much less risk. Dose limits apply to exposure of the public and medical staff from patients. Previously, the ICRP has recommended that a source-related dose constraint for optimisation of a few mSv/episode applies to relatives, visitors, and caregivers at home, rather than a dose limit. The present report recommends that young children and infants, as well as visitors not engaged in direct care or comforting, should be treated a s members of the public (i.e. be subject to the public dose limit.) The modes of exposure to other people are: external exposure; internal exposure due to contamination; and environmental pathways. Dose to adults from patients is mainly due to external exposure. Contamination of infants and children with saliva from a patient could result in significant doses to the child's thyroid. It is important to avoid contamination of children and pregnant women. After radioiodine therapy, mothers must cease breastfeeding immediately. Many types of therapy with unsealed radionuclides are contraindicated in pregnant females. Women should not become pregnant for some time after radioisotope therapy. Technetium-99m dominates discharges to the environment from excreta of nuclear medicine patients, but its short half-life limits its importance. The second largest discharges, iodine-131, can be detected in the environment after medical uses but with no measurable environmental impact. Storing patient's urine after therapy appears to have minimal benefit. Radionuclides released into modern sewage systems are likely to result in doses to sewer workers and the public that are well below public dose limits. The decision to hospitalise or release a patient should be determined on an individual basis. In addition to residual activity in the patient, the decision should take many other factors into account. Hospitalisation often involves a significant psychological burden as well as monetary and other costs that should be analysed and justified. Patients travelling after radioiodine therapy rarely present a hazard to other passengers if travel times are limited to a few hours. Environmental or other radiation-detection devices are able to detect patients who have had radioiodine therapy for several weeks after treatment. Personnel operating such detectors should be specifically trained to identify and deal with nuclear medicine patients. Records of the specifics of therapy with unsealed radionuclides should be maintained at the hospital and given to the patient along with written precautionary instructions. In the case of death of a patient who has had radiotherapy with unsealed radionuclides in the last few months, special precautions may be required.

Fósforo 32. Experiencia de 30 años en la policitemia vera / Thirty years of experience in the use of 32 phosphorus for Polycythemia Vera

Se realizó un estudio retrospectivo de 279 pacientes con policitemia vera (PV) de los cuales 72 (25,8 por ciento) fueron tratados con 32P con un tiempo de seguimiento entre 4 y 28 años. La edad promedio fue de 61 años al recibir el primer tratamiento. El control hematológico se obtuvo en el 95,8 por ciento de los casos (n=69). La media de duración del control hematológico fue de 27,8 meses. La media de la dosis total utilizada por paciente fue de 9.2 ± 8,9 mCi. En 34 pacientes (54,1 por ciento) fue necesaria la administración de más de una dosis del radiofármaco durante el tiempo de evolución de la enfermedad. Del total de pacientes tratados, 5 (6,9 por ciento) desarrollaron una leucemia aguda entre los 9 y 25 años posteriores a la primera administración y 3 (4,1 por ciento) desarrollaron otras malignidades después de más de 15 años del diagnóstico. La mediana de supervivencia postratamiento fue de 10,1 años y la causa fundamental de muerte fueron los accidentes vasculares. No hay dudas de que el 32P constituye un método terapéutico conveniente y eficaz, fundamentalmente en pacientes mayores de 60 años, que logra una excelente calidad de vida y prolonga la supervivencia con un mínimo de reacciones adversas y un costo moderado(AU)

[Hydroxyurea--is it a harmless drug in Vaquez disease?]]. / L'Hydroxy-Urée est-elle une drogue innocente dans la maladie de Vaquez?

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.

Treatment of the myeloproliferative disorders with 32P.

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?

[Polycythaemia vera--diagnosis and therapy]. / Polycythaemia vera--Diagnostik und Therapie.

Polycythaemia vera is a clonal myeloproliferative disorder mainly involving proliferation of the erythropoiesis. The symptoms are varied and usually unspecific. The most serious complications of the disease are a thrombotic tendency and myeloid metaplasia. Thromboses mainly (2/3) occur in the arterial and less often (1/3) in the venous system and are the most common cause of death. Criteria have been established for the diagnosis of polycythaemia vera which should be strictly observed in order to distinguish between this disease, spurious polycythaemia, essential thrombocythaemia and secondary erythrocytosis. The goal of treatment is the prevention of thromboembolic complications and of myeloid metaplasia. The initial treatment always consists of phlebotomies until a hematocrit < 45% is achieved. The decision regarding maintenance therapy is difficult. While hydroxyurea or radiophosphorus is the treatment of choice in older patients (> 70 years of age), it is more difficult to select the appropriate therapy for younger patients (< 60 years), since recent studies have indicated that hydroxyurea treatment might increase the risk of leukemia. Interferon is effective but its role in the treatment of polycythaemia vera has not been established.

Treatment of polycythaemia vera and essential thrombocythaemia.

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.

Use of radioactive phosphorus in haematology.

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.

Treatment of polycythemia vera: use of 32P alone or in combination with maintenance therapy using hydroxyurea in 461 patients greater than 65 years of age. The French Polycythemia Study Group.

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.

Outcome of 259 patients with primary proliferative polycythaemia (PPP) and idiopathic thrombocythaemia (IT) treated in a regional nuclear medicine department with phosphorus-32--a 15 year review.

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.