Assuntos
Encéfalo/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/líquido cefalorraquidiano , Toxoplasmose Cerebral/patologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Ciclofosfamida/uso terapêutico , Febre/etiologia , Cefaleia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Agonistas Mieloablativos/uso terapêutico , Reação em Cadeia da Polimerase , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/microbiologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vômito/etiologiaRESUMO
Tyrosine kinase inhibitors (TKIs) are currently the first line treatment for chronic myelogenous leukemia (CML) in countries with high and intermediate-high gross national income. Hematopoietic cell transplantation (HCT) in these countries is considered salvage therapy for eligible patients who failed TKI or progress to advanced disease stages. In Latin America, treatment for CML also changed with availability of TKI in the region. However, many challenges remain, as the cost of this class of medication and recommended monitoring is high. CML treatment practices in Latin America demonstrate that the majority of patients are treated with TKI at some point after diagnosis, most commonly imatinib mesylate, but still TKI can only be used after interferon failure in some countries. Other treatment practices are different from established international guidelines, outlying the importance of continuing medical education. Allogeneic HCT is a treatment option for CML in this region and could be considered a cost-effective approach in a small subset of young patients with available donors, as the overall cost of long-term non-transplant treatment may surpass the cost of transplantation. However, there are many challenges with HCT in Latin America such as access to experienced transplant centers, donor availability, and cost of essential drugs used after transplant, which further impacts expansion of this treatment approach in patients in need. In conclusion, Latin American patients with CML have access to state of the art CML treatment. Yet, drug costs have a tremendous impact on developing health systems. Optimization of CML treatment in the region with appropriate monitoring, recognizing patients who would be transplant candidates, and expanding access to transplantation for eligible patients may curtail these costs and further improve patient care.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adulto , Países em Desenvolvimento , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , América Latina/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Transplante HomólogoRESUMO
Bone marrow transplantation (BMT) has become an accepted and important medical intervention which has become a routine part of medical practice. Its utility has, however, been questioned recently in a number of diseases in which its role has been clearly established on the basis that there are better non-transplant therapeutic options. The suspicion that these moves to eradicate BMT as an option may not stem from purely scientific reasons has prompted the preparation of these personal reflections. I will focus this discussion only on two diseases in which BMT has been shown to be useful: chronic myelogenous leukemia (CML) and multiple myeloma (MM).
Assuntos
Transplante de Medula Óssea/tendências , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Benzamidas , Transplante de Medula Óssea/economia , Transplante de Medula Óssea/estatística & dados numéricos , Países Desenvolvidos/economia , Países em Desenvolvimento/economia , Custos de Medicamentos , Uso de Medicamentos/economia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Melfalan/administração & dosagem , Melfalan/economia , México , Mieloma Múltiplo/cirurgia , Piperazinas/economia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Espanha , Condicionamento Pré-Transplante/economia , Transplante Autólogo/economia , Transplante Homólogo/economia , Resultado do Tratamento , Estados UnidosRESUMO
Although the drug imatinib has been accepted as the treatment of choice for chronic myelogenous leukemia (CML) in chronic phase (CP) throughout the Western world, allogeneic stem cell transplantation (allo-SCT) continues to remain a widely practiced first-line treatment in countries with limited health care budgets. The rationale is not scientific, but largely economically based. We analyzed a cohort of 46 CML patients who participated in a graft-versus-host disease (GVHD) prophylaxis clinical trial and underwent related HLA-matched allogeneic peripheral blood stem cell transplantation. The median time of follow-up in surviving patients was 43 months (range: 4-89 months). Risk stratification of the population was done by European Blood and Marrow Transplant (EBMT) criteria. The estimated probabilities of overall survival (OS) and leukemia-free survival (LFS) at 3 years in low EBMT risk score (0-2) patients were both 91%, respectively. We conclude that in countries with restricted access to imatinib, allo-SCT should be considered early on as front-line therapy. Continued research support for bone marrow transplantation will be needed to make a global impact on this disease.
Assuntos
Transplante de Medula Óssea/economia , Tratamento Farmacológico/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Adolescente , Adulto , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Benzamidas , Transplante de Medula Óssea/métodos , Criança , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/economia , Transplante de Células-Tronco de Sangue Periférico/métodos , Piperazinas/economia , Piperazinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Recidiva , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
CD34+ peripheral blood hematopoietic stem cells (HSC) are usually collected following mobilization therapy accomplished by using growth factors (GF) such as rHuG-CSF or rHuGM-CSF with or without chemotherapy. A target dose of yielded CD34+ is usually prescribed by the attending physician depending on different protocols, which may include single or double transplantation. HSC collection usually is performed when at least 20 CD34+ HSC/microL are detected by means of flow cytometry. A cumulative dose of at least 2 x 10(6)/Kg/bw CD34+ HSC has been considered as the threshold to allow a prompt and persistent hematopoietic recovery. Unfortunately, this goal is not achieved by the totality of patients undergoing mobilization regimen. In fact, 5-46% of patients who underwent mobilization therapy fail HSC collection due to very low peripheral blood HSC CD34+ count. Patients' characteristics, including age, sex, stage of the underlying disease (complete or partial remission), diagnosis, previously administered radio/chemotherapy regimens, time-lapse from last chemotherapy before mobilization and mobilization schedule (including dose of GF) were considered as possibly predictive of poor or failed mobilization. We performed a retrospective analysis in 2177 patients from three large Italian academic institutions to assess the incidence of poor mobilizers within our patients' series. Therefore, a patient who fails a first mobilization (and when an HLA-compatible related on unrelated donor is not available) could undergo a second attempt either with different mobilization schedule or by using different GF, such as stem cell factor, growth hormone (GH), or more recently newly introduced drugs such as AMD3100, alone or in combination with rHuG- or -rHuGM-CSF. Thus, we investigated the fate of those who failed a first mobilization and subsequently underwent a second attempt or alternative therapeutic approaches.
Assuntos
Neoplasias/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Antígenos CD34/sangue , Seguimentos , Hematopoese , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Linfocítica Crônica de Células B/cirurgia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide Aguda/cirurgia , Linfoma não Hodgkin/cirurgia , Mieloma Múltiplo/cirurgia , Neoplasias/mortalidade , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. METHODS: An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. RESULTS: Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. CONCLUSION: These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.
Assuntos
Anemia Aplástica/cirurgia , Doença Enxerto-Hospedeiro/cirurgia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia/cirurgia , Linfoma não Hodgkin/cirurgia , Seleção de Pacientes , Padrões de Prática Médica , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Crise Blástica/cirurgia , Tomada de Decisões , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Transplante de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Imunossupressores/uso terapêutico , Internet , Leucemia/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Qualidade da Assistência à Saúde , Características de Residência , Inquéritos e Questionários , Condicionamento Pré-Transplante , Transplante HomólogoAssuntos
Transplante de Células-Tronco Hematopoéticas/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Benzamidas , Países Desenvolvidos/classificação , Países Desenvolvidos/economia , Custos de Medicamentos , Europa (Continente)/epidemiologia , Custos de Cuidados de Saúde , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Mesilato de Imatinib , Renda , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Piperazinas/economia , Piperazinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Sociedades Médicas/estatística & dados numéricos , Transplante Homólogo/economia , Transplante Homólogo/estatística & dados numéricosAssuntos
Países Desenvolvidos/economia , Países em Desenvolvimento/economia , Terapêutica/economia , Adolescente , Idade de Início , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Benzamidas , Transplante de Medula Óssea/economia , Doença Catastrófica/economia , Criança , China/epidemiologia , Custos de Medicamentos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/economia , Custos de Cuidados de Saúde , Alocação de Recursos para a Atenção à Saúde/economia , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Direitos Humanos , Humanos , Mesilato de Imatinib , Renda , Índia/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Pessoa de Meia-Idade , Piperazinas/economia , Piperazinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Justiça Social , Medicina Estatal/economiaRESUMO
Imatinib mesylate represents the first of a new generation of molecularly targeted therapies engineered to disrupt signal transduction pathways. It is a tyrosine kinase inhibitor with relatively selective activity against the Abelson (ABL) proto-oncogene, platelet-derived growth factor receptor, and c-KIT receptor. Deregulated tyrosine kinase activity has been implicated as a central pathogenic event in a number of human malignancies, most notably chronic myeloid leukemia. In this myeloproliferative disorder the t(9;22) reciprocal translocation results in the generation of a novel fusion oncoprotein, BCR-ABL, with constitutive tyrosine kinase activity. Imatinib inhibits this activity, inducing remarkable rates of hematological and cytogenetic remission in excess of those seen with alternative medical therapies. Following a large phase III study comparing its efficacy with the combination of interferon alpha and low-dose cytarabine, it has emerged as the current gold standard therapy for patients with chronic-phase disease without a potential bone marrow donor and those considered unsuitable for bone marrow transplantation. Its integration into the management of those patients who might be considered for transplantation, which has historically been considered the only potentially curative approach, remains a major challenge. The increasing recognition and subsequent molecular characterization of resistance mechanisms has reinforced the need to exercise caution against deferring a proven curative therapy in favor of a treatment approach that is still investigational, with the spectre of increased numbers of patients progressing to sudden-onset blast crisis remaining the potential dark cloud in the silver lining for imatinib.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Piperazinas/efeitos adversos , Piperazinas/economia , Proto-Oncogene Mas , Pirimidinas/efeitos adversos , Pirimidinas/economiaRESUMO
PURPOSE: To determine the frequency and nature of changes to the brain resulting from chemotherapy, radiation therapy, and bone marrow transplantation for chronic myeloid leukemia and to compare the sensitivity of conventional and registered MR scans for detecting these changes. METHODS: In 15 patients, conventional T1-weighted, T2-weighted, and fluid-attenuated inversion recovery MR sequences, as well as T1-weighted radio frequency spoiled 3-D volume MR scans were performed before, 4 to 6 days after, and up to 339 days after transplantation (13 allografts, two autografts). A subvoxel registration program was used to match the volume images precisely so that small changes could be detected after subtraction of scans. Five healthy adult control subjects were also studied on two occasions 1 month apart. RESULTS: Studies performed 4 to 339 days after transplantation showed ventricular enlargement and cortical atrophy in all 13 patients who had allografts. The changes were evident at 4 to 6 days after transplantation and became more obvious during later follow-up examinations. Similar changes were seen in one patient with an autograft but no significant change was seen in the other patient with an autograft or in the five control subjects. Accurately registered volume scans were more sensitive than unregistered conventional scans in detecting early (9/10 versus 0/10), intermediate (12/13 versus 3/12), and late (10/10 versus 4/9) ventricular enlargement on follow-up examinations. The same applied to cortical atrophy (9/10 versus 0/10, 12/13 versus 0/12, and 10/10 versus 0/9). CONCLUSION: The specific cause and clinical significance of these changes are uncertain. Subvoxel registration of serial MR images may reveal changes that are poorly seen or not apparent on conventional scans.
Assuntos
Transplante de Medula Óssea , Encéfalo/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Atrofia , Córtex Cerebral/patologia , Ventrículos Cerebrais/patologia , Feminino , Humanos , Masculino , Meninges/patologia , Pessoa de Meia-Idade , Período Pós-Operatório , Técnica de SubtraçãoAssuntos
Reembolso de Seguro de Saúde/legislação & jurisprudência , Medicaid/legislação & jurisprudência , Transplante de Órgãos/economia , Arizona , Feminino , Alocação de Recursos para a Atenção à Saúde/legislação & jurisprudência , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Responsabilidade Legal/economia , Medicaid/economia , Transplante de Órgãos/legislação & jurisprudência , Planos Governamentais de Saúde/economia , Planos Governamentais de Saúde/legislação & jurisprudência , Estados UnidosRESUMO
The Polymerase Chain Reaction (PCR) was used to evaluate minimal residual disease in 21 Ph+ CML patients at various intervals after allogeneic bone-marrow transplantation (ABMT) by amplification of bcr-abl cDNA. All patients were cytogenetically Ph- at the moment of molecular analysis. Of these 76% were PCR negative, 24% positive for bcr-abl transcripts. 100% of the Cyclosporine A/Methotrexate treated patients (7/7) were negative. Severe chronic GvHD was twice as frequent in PCR positive patients (60%) than in negative ones (31%). The only patient who relapsed during follow up was PCR positive. The two longest survivors were PCR negative. These data are still insufficient for assessing the predictive value of PCR analysis in CML. Patients. 25 patients with Ph+ CML at diagnosis were enrolled in this study. Two died soon after BMT because of infection for failure of engraftment/early relapse, two were Ph chromosome positive and PCR+, and were therefore dismissed from this study. All remaining 21 patients were cytogenetically Ph- at the time of molecular analysis and underwent ABMT from matched donors. All patients were conditioned with cyclophosphamide and TBI: 330 cGy the three days prior to transplantation (990 cGy total, treatment B), or 200 cGy two times daily for three days (1200 cGy total, treatment A). In 3 cases the marrow was treated for GvHD prophilaxis with Campath alone or Campath plus BT 5/9 monoclonal antibodies (1). All patients were treated with Cyclosporin A (CS) 5 mg/kg i.v. from the day prior to transplantation until 25-30 days after; 9 of these were treated with CS plus Methotrexate (MTX).
Assuntos
Biomarcadores Tumorais/análise , Transplante de Medula Óssea , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , RNA Mensageiro/análise , RNA Neoplásico/análise , Quimera , Ciclosporinas/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Reação em Cadeia da Polimerase , Indução de RemissãoRESUMO
Marrow ablation with cytotoxic drugs and/or total body irradiation followed by allogeneic bone marrow transplantation from an HLA-identical sibling cures many patients with acute and chronic myeloid leukaemia. We have obtained good results with this treatment. Up to now the necessary funds to cover the minimal requirements for transplantations in Norway have not been granted. It is now possible to use unrelated, HLA-matched donors, which will more than double the need for allogeneic bone marrow transplantations within a few years. This article discusses indications, results, costs and practical procedures connected to allogeneic bone marrow transplantation for leukaemia in adults.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide Aguda/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Adulto , Transplante de Medula Óssea/economia , Transplante de Medula Óssea/métodos , Feminino , Humanos , Masculino , PrognósticoAssuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , American Medical Association , Transplante de Medula Óssea/métodos , Terapia Combinada , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Pessoa de Meia-Idade , Avaliação da Tecnologia Biomédica , Doadores de Tecidos , Transplante Homólogo , Estados UnidosRESUMO
The cost of bone-marrow transplantation is compared in 4 diseases: acute myelogenous leukaemia, severe combined immunodeficiency, severe aplastic anaemia and chronic granulocytic leukaemia. Hospital cost components directly related to the clinical protocols applied are valorized. Results confirm the well-known fact that bone-marrow transplantation is a costly technique. The unit cost of a transplantation can vary from 1 to 2 between departments for the sole reason that patients treated are not suffering from the same illness. For one disease, the unit cost may vary from 1 to 2.7 when post-graft complications arise. Furthermore, in the health-care sector, as well as in every other economic sector, costs do not remain stable: they vary in time most especially when treatment protocols evolve. This type of cost information is the basis for management control systems without which physicians, hospital managers and health-care authorities cannot communicate effectively. In countries where health care is largely financed by the community, what is at stake is the future of advanced technologies in medicine.