RESUMO
Conforme novos tratamentos e tecnologias surgiram, vemos cada vez mais casos de neoplasias curadas com quimioterapia, radioterapia e cirurgia. Com esse aumento de pacientes curados, começamos a identificar efeitos adversos graves que podem se apresentar até mais de 10 anos após o primeiro tratamento. Dentre essas complicações, algumas das piores são as neoplasias secundárias. Traremos a seguir um relato de caso de um homem jovem que foi diagnosticado com cancer de mama aos 28 anos como consequência do tratamento da leucemia linfoide aguda que teve aos 7 anos de idade, o qual envolvia irradiação de corpo inteiro (TBI) seguido de transplante alogênico. Nossa conclusão é que esses pacientes que recebem TBI devem ter um acompanhamento mais de perto durante toda a vida e com medidas de rastreio mais precoces e individualizadas
As new treatments and technologies have emerged, we see more and more cases of cancer cured with chemotherapy, radiotherapy and surgery. With the increase in cured patients, we began to identify serious adverse effects that can appear even more than 10 years after the first treatment. Among these complications, one of the worst are secondary neoplasms. We will now present a case report of a young man who was diagnosed with breast cancer at the age of 28 as a result of the treatment for acute lymphocytic leukemia that he had at the age of 7, which involved total body irradiation (TBI) followed by allogenic transplantation. Our conclusion is that those patients who receive TBI should have a lifelong closer follow-up and with earlier and more individualized screening measures
Assuntos
Humanos , Masculino , Transplante Homólogo , Irradiação Corporal Total , Neoplasias da Mama Masculina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia-Linfoma Linfoblástico de Células PrecursorasRESUMO
The purpose of this study is to describe the commissioning of a novel three-dimensional arc-based technique for total body irradiation (TBI) treatments. The development and implementation of this technique allowed our institution to transition from a bilateral two-dimensional (2D) technique to a methodology based on volumetric dose calculation. The methodology described in this work is a derivation from the MATBI technique, with the static fields being replaced by four contiguous arc-fields for each anterior and posterior incidence. The reduced number of fields we employed makes it possible to reach a satisfactory dose uniformity through manual optimization in a straightforward process. We use the Eclipse anisotropic analytical algorithm (AAA) algorithm, commissioned with preconfigured beam data for a 6 MV photon beam, at standard SSD (100 cm). A thorough evaluation of the accuracy of the AAA algorithm at an extended distance (approximately 200 cm) was carried out. For the evaluation, we compared measured and calculated percentage depth-dose and profiles that included open-field, penumbra, and out-of-field regions. The analysis was performed for both static and arc fields, taking into consideration unshielded fields and also in the presence of lung shielding blocks. End-to-end tests were carried out for our institutional template plan by two means: with a 2D ion chamber array detector in solid phantom and using Gafchromic films in an anthropomorphic phantom. The results obtained in this work demonstrate that the Eclipse AAA algorithm commissioned for standard treatments can be safely used with our TBI planning technique. Moreover, this technique proved to be a highly efficient path to replace conventional treatment techniques, providing a homogeneous dose distribution, dosimetric robustness, and shorter treatment times. In addition, as inherited from the MATBI technique, our methodology can be implemented in small treatment rooms, with no need for ancillary equipment.
Assuntos
Planejamento da Radioterapia Assistida por Computador , Irradiação Corporal Total , Algoritmos , Humanos , Imagens de Fantasmas , Radiometria , Dosagem RadioterapêuticaRESUMO
OBJECTIVES: To assess the craniofacial skeletal growth in pediatric hematopoietic stem-cell transplantation (HSCT) survivors in comparison with age-sex matched-paired controls. METHODS: A case-controlled retrospective comparison of the craniofacial growth in 25 HSCT children and 25 matched-paired controls was conducted. Craniofacial growth was quantitatively assessed by linear and angular measurements in panoramic radiographic images using ImageJ¯. Stature growth and body weight were obtained through physical examination. Cancer diagnosis, myeloablative conditioning, and HSCT were retrieved from medical records. RESULTS: Patients aged 12.2 years (±3.8; 16 male, 9 female). Radiographic images were obtained on an average of 2.43 (±2.0) years after HSCT. The main malignant diagnosis was acute lymphoblastic leukemia (56%), followed by acute myeloid leukemia (36%) and myelodysplastic syndromes (8%). Total body irradiation was associated with chemotherapy at 80%. Mean age at transplantation was 10 (±4.7) years. HSCT survivors showed reduced a vertical growth of the mandibular ramus (p=0.003). This persisted among individuals below 12 years of age (p=0.017). The HSCT group showed delayed dental eruption, though there was no statistically significant difference (p=0.3668). The HSCT group showed stature deficit, increased weight, and body mass index (Z-score stature: -0.28; Z-score weight: 0.38, respectively). CONCLUSIONS: Pediatric HSCT has decreased vertical craniofacial growth compared to their matched controls. There might be an association between reduced craniofacial vertical growth and reduced estature growth. Further studies to quantitatively investigate the impact of different myeloablative regimens in craniofacial skeletal growth and development.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante , Irradiação Corporal Total/efeitos adversosRESUMO
Introducción: La aplasia medular adquirida grave es una enfermedad hematológica infrecuente caracterizada por una disminución o ausencia de precursores hematopoyéticos en la médula ósea, lo cual se expresa con distintos grados de citopenias. Varios factores, infecciosos o no, pueden incidir en su origen. Su manejo es complejo y puede incluir tratamiento inmunosupresor y trasplante de progenitores hematopoyéticos alogénico. Objetivo: Demostrar la utilidad de la realización del trasplante de progenitores hematopoyéticos alogénico haploidéntico en pacientes con aplasia medular grave. Caso clínico: Paciente masculino de 21 años de edad, con antecedentes de salud, que en octubre del 2018 debutó con íctero, pancitopenia, lesiones purpúrico hemorrágicas en piel y mucosas, en el curso de una hepatitis aguda seronegativa. La biopsia de médula ósea mostró aplasia medular severa. Se inició tratamiento inmunosupresor con globulina antitimocίtica, ciclosporina A y metilprednisolona. Al cabo de los 6 meses mantenía trombocitopenia severa con necesidades transfusionales y en octubre de 2019 se decide realizar trasplante de progenitores hematopoyéticos alogénico con donante haploidéntico y empleando como tratamiento acondicionante globulina antitimocίtica, fludarabina, ciclofosfamida y bajas dosis de irradiación corporal total. En evaluación clίnica de julio de 2020 (dίa + 280 del trasplante) el paciente estaba asintomático y con parámetros hematológicos normales. Conclusiones: Se demostró que el trasplante de progenitores hematopoyéticos alogénico haploidéntico es un proceder realizable y útil en pacientes con aplasia medular grave, lo cual corrobora el beneficio clínico que puede aportar su ejecución en pacientes con esta enfermedad(AU)
Introduction: Acquired severe marrow aplasia is a rare hematological disease characterized by decrease or absence of hematopoietic precursors in bone marrow, which is expressed with different degrees of cytopenias. Several factors, infectious or not, can influence its origin. Its management is complex and may include immunosuppressive treatment and allogeneic hematopoietic stem-cell transplantation. Objective: To demonstrate the usefulness of performing haploidentical allogeneic hematopoietic stem-cell transplantation in patients with severe medullary aplasia. Clinical case: A 21-year-old male patient, with medical history, who first presented, in October 2018, with icterus, pancytopenia, as well as purpuric hemorrhagic lesions on the skin and mucosa, in the course of acute seronegative hepatitis. The bone marrow biopsy showed severe marrow aplasia. Immunosuppressive treatment was started with antithymocytic globulin, cyclosporine A, and methylprednisolone. After six months, he maintained severe thrombocytopenia under transfusion requirements and, in October 2019, the decision was to perform allogeneic hematopoietic stem-cell transplantation with a haploidentical donor and using antithymocyte globulin, fludarabine, cyclophosphamide, and low doses of total body irradiation as conditioning treatment. In the clinical assessment carried out in July 2020 (day +280 after transplantation), the patient was asymptomatic and with normal hematological parameters. Conclusions: Transplantation of haploidentic allogeneic hematopoietic progenitors was shown to be a feasible and useful procedure in patients with severe marrow aplasia, which corroborates the clinical benefit that its execution can bring in patients with this disease(AU)
Assuntos
Humanos , Masculino , Adulto Jovem , Doadores de Tecidos/ética , Metilprednisolona/uso terapêutico , Irradiação Corporal Total/métodos , Microscopia Eletrônica de Transmissão e Varredura/métodos , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas/métodos , Cuba , Transplante Haploidêntico/métodos , Anemia Aplástica/terapia , Soro AntilinfocitárioRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 ± 5 days and 16 ± 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD. This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Nanopartículas , Adulto , Idoso , Medula Óssea , Etoposídeo/uso terapêutico , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/terapia , Lipídeos , Pessoa de Meia-Idade , Projetos Piloto , Condicionamento Pré-Transplante , Transplante Homólogo , Irradiação Corporal Total , Adulto JovemRESUMO
OBJECTIVES: To assess the craniofacial skeletal growth in pediatric hematopoietic stem-cell transplantation (HSCT) survivors in comparison with age-sex matched-paired controls. METHODS: A case-controlled retrospective comparison of the craniofacial growth in 25 HSCT children and 25 matched-paired controls was conducted. Craniofacial growth was quantitatively assessed by linear and angular measurements in panoramic radiographic images using ImageJ¯. Stature growth and body weight were obtained through physical examination. Cancer diagnosis, myeloablative conditioning, and HSCT were retrieved from medical records. RESULTS: Patients aged 12.2 years (±3.8; 16 male, 9 female). Radiographic images were obtained on an average of 2.43 (±2.0) years after HSCT. The main malignant diagnosis was acute lymphoblastic leukemia (56%), followed by acute myeloid leukemia (36%) and myelodysplastic syndromes (8%). Total body irradiation was associated with chemotherapy at 80%. Mean age at transplantation was 10 (±4.7) years. HSCT survivors showed reduced a vertical growth of the mandibular ramus (p=0.003). This persisted among individuals below 12 years of age (p=0.017). The HSCT group showed delayed dental eruption, though there was no statistically significant difference (p=0.3668). The HSCT group showed stature deficit, increased weight, and body mass index (Z-score stature: -0.28; Z-score weight: 0.38, respectively). CONCLUSIONS: Pediatric HSCT has decreased vertical craniofacial growth compared to their matched controls. There might be an association between reduced craniofacial vertical growth and reduced estature growth. Further studies to quantitatively investigate the impact of different myeloablative regimens in craniofacial skeletal growth and development.
Assuntos
Humanos , Masculino , Feminino , Criança , Leucemia Mieloide Aguda , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Irradiação Corporal Total/efeitos adversos , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: Immunoglobulin-cytokine fusion molecules have been shown to be the new generation of immunomodulating agents in transplantation tolerance induction. In the present study, we tested whether immunoregulatory cytokine fusion proteins of IL-10/Fc, TGF-ß/Fc, or IL-2/Fc would enhance allogeneic bone marrow cell (BMC) engraftment and promote tolerance induction. METHODS: B6 (H2) mice were conditioned with anti-CD154 (MR1) and rapamycin (Rapa) plus 100 cGy total body irradiation (MR1/Rapa/100 cGy) and transplanted with allogeneic B10.D2 (H2) BMC. Recipients were treated with lytic IL-2/Fc, nonlytic IL-2/Fc, TGF-ß/Fc, or IL-10/Fc fusion proteins to promote chimerism to induce tolerance. RESULTS: Donor chimerism was achieved in 20% of recipients conditioned with MR1/Rapa/100 cGy. The addition of TGF-ß/Fc (5- or 10-day treatment) or nonlytic IL-2/Fc (10-day treatment) fusion proteins to the conditioning resulted in engraftment in nearly 100% of recipients. In contrast, lytic IL-2/Fc or IL-10/Fc had no effect. The combination of nonlytic IL-2/Fc and TGF-ß/Fc had a synergistic effect to promote engraftment and resulted in significantly higher donor chimerism compared with recipients conditioned with TGF-ß/MR1/Rapa/100 cGy. Engraftment was durable in the majority of chimeras and increased over time. The chimeras accepted donor skin grafts and promptly rejected third-party skin grafts. Moreover, specific T cell receptor-Vß5.½ and TCR-Vß11 clonal deletion was detected in host T cells in chimeras, suggesting central tolerance to donor alloantigens. CONCLUSIONS: Allogeneic BMC engraftment is enhanced with TGF-ß/Fc fusion protein treatment. TGF-ß/Fc and nonlytic IL-2/Fc exert a synergistic effect in promotion of alloengraftment and donor-specific transplant tolerance, significantly decreasing the minimum total body irradiation dose required.
Assuntos
Transplante de Medula Óssea , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/farmacologia , Imunossupressores/farmacologia , Interleucina-2/farmacologia , Transplante de Pele , Fator de Crescimento Transformador beta/farmacologia , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Tolerância ao Transplante/efeitos dos fármacos , Animais , Transplante de Medula Óssea/efeitos adversos , Células Cultivadas , Técnicas de Cocultura , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/imunologia , Rejeição de Enxerto/imunologia , Isoantígenos/imunologia , Camundongos Endogâmicos C57BL , Modelos Animais , Proteínas Recombinantes de Fusão/farmacologia , Sirolimo/farmacologia , Transplante de Pele/efeitos adversos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fatores de Tempo , Transplante Homólogo , Irradiação Corporal TotalRESUMO
The aim of this study was the calculation of conversion coefficients for absorbed doses per fluence (DT/Φ) using the sitting and standing male hybrid phantom (UFH/NCI) exposure to monoenergetic protons with energy ranging from 2 MeV to 10 GeV. Sex-averaged effective dose per fluence (E/Φ) using the results of DT/Φ for the male and female hybrid phantom in standing and sitting postures were also calculated. Results of E/Φ of UFH/NCI standing phantom were also compared with tabulated effective dose conversion coefficients provided in ICRP publication 116. To develop an exposure scenario implementing the male UFH/NCI phantom in sitting and standing postures was used the radiation transport code MCNPX. Whole-body irradiations were performed using the recommended irradiation geometries by ICRP publication 116 antero-posterior (AP), postero-anterior (PA), right and left lateral, rotational (ROT) and isotropic (ISO). In most organs, the conversion coefficients DT/Φ were similar for both postures. However, relative differences were significant for organs located in the lower abdominal region, such as prostate, testes and urinary bladder, especially in the AP geometry. Results of effective dose conversion coefficients were 18% higher in the standing posture of the UFH/NCI phantom, especially below 100 MeV in AP and PA. In lateral geometry, the conversion coefficients values below 20 MeV were 16% higher in the sitting posture. In ROT geometry, the differences were below 10%, for almost all energies. In ISO geometry, the differences in E/Φ were negligible. The results of E/Φ of UFH/NCI phantom were in general below the results of the conversion coefficients provided in ICRP publication 116.
Assuntos
Imagens de Fantasmas , Prótons , Doses de Radiação , Irradiação Corporal Total , Feminino , Humanos , Masculino , Método de Monte Carlo , Neoplasias/radioterapia , Postura , Proteção RadiológicaRESUMO
OBJECTIVES: This study aimed to present a comparison of iodine-131 (I) biokinetics and radiation doses to red-marrow (rm) and whole-body (wb), following the administration of tracer and therapeutic activities, as a means of confirming whether I clearance and radiation doses for therapy procedures can be predicted by tracer activities. METHODS: Eleven differentiated thyroid cancer patients were followed after receiving tracer and therapeutic I activity. Whole-body I clearance was estimated using radiation detectors and OLINDA/EXM software was used to calculate radiation doses to rm and wb. RESULTS AND DISCUSSION: Tracer I activity of 86 (±14) MBq and therapeutic activity of 8.04 (±1.18) GBq were administered to patients, thereby producing an average wb I effective half-time and residence time of, respectively, 13.51 (±4.05) and 23.13 (±5.98) h for tracer activities and 13.32 (±3.38) and 19.63 (±4.77) h for therapy. Radiation doses to rm and wb were, respectively, 0.0467 (±0.0208) and 0.0589 (±0.0207) mGy/MBq in tracer studies and 0.0396 (±0.0169) and 0.0500 (±0.0163) mGy/MBq in therapy. Although the differences were not considered statistically significant between averages, those between the values of effective half-times (P=0.906), residence times (P=0.145), and radiation doses to rm (P=0.393) and to wb (P=0.272), from tracer and therapy procedures, large differences of up to 80% in wb I clearance, and up to 50% in radiation doses were observed when patients were analyzed individually, thus impacting on the total amount of I activity calculated to be safe for application in individual therapy. CONCLUSION: I biokinetics and radiation doses to rm and wb in therapy procedures are well predicted by diagnostic activities when average values of a group of patients are compared. Nonetheless, when patients are analyzed individually, significant differences may be encountered, thus implying that nuclear medicine therapy-planning requires due consideration of changes in individual patient-body status from initial tracer to final therapy procedures to thus provide appropriate adjustments in therapeutic activities.
Assuntos
Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Medicina Nuclear , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador , Adulto , Medula Óssea/efeitos da radiação , Feminino , Meia-Vida , Humanos , Cinética , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Irradiação Corporal TotalRESUMO
BACKGROUND/AIM: The aim of this study was to evaluate the expression of FASL, FAS and FADD and caspase-3 in oesophagus, stomach and colonic tissues of mice irradiated in vivo by immunohistochemistry. MATERIALS AND METHODS: A total of 48 adult male C57BL mice were distributed into four groups: Ami(-)/Rad(-): Mice received 0.5 ml of 0.9% physiological saline solution (PPS) intraperitioneally (i.p.); Ami(+)/Rad(-): mice received amifostine (400mg/kg i.p.) freshly dissolved in double-distilled water; Ami(-)/Rad(+): mice received 0.5 ml of PSS i.p. 30 min before a single whole-body radiation dose of 7 Gy; Ami(+)/Rad(+): mice received 0.5 ml of an aqueous solution of 400 mg/kg amifostine i.p.30 min prior to irradiation. All groups were assigned into subgroups sacrificed at 0.5 h, 1 h, 2 h and 4 h after irradiation. RESULTS: In oesophagus and stomach tissues, we did not observe any difference between Ami(-)/ad(-), Ami(+)/Rad(-), Ami(-)/Rad(+) and Ami(+)/Rad(+) groups in the expression of FASL, FAS and FADD. The colonic tissue was the only to exhibit any difference in the expression of FAS and caspase-3 protein in the Ami(-)/Rad(+)group at 1 and 2 h. Amifostine increased FAS and caspase-3 immunoexpression when compared to the control. Immunoexpression for FASL and FADD was not remarkably different in colonic tissue. CONCLUSION: Taken together, our results demonstrate that amifostine increases FAS and caspase-3 expression in colonic tissue of irradiated mice.