Asunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/metabolismo , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Estudios Cruzados , HumanosRESUMEN
We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA.
Asunto(s)
Ciclofosfamida/administración & dosificación , Anemia de Fanconi/terapia , Depleción Linfocítica/métodos , Trasplante Haploidéntico/métodos , Niño , Preescolar , Esquema de Medicación , Anemia de Fanconi/mortalidad , Femenino , Humanos , Inmunosupresores/administración & dosificación , Masculino , Linfocitos TAsunto(s)
Trasplante de Médula Ósea , Femenino , Humanos , Masculino , Publicaciones Periódicas como Asunto , América del SurRESUMEN
Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea , Ciclofosfamida/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/administración & dosificación , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Bronchiolitis obliterans (BO) is a severe pulmonary complication of allo-SCT. This study evaluated the incidence of BO in patients undergoing allo-SCT in Hospital Universitário da Universidade Federal do Paraná, risk factors for developing this complication and prognostic factors for those patients who developed this entity. The study included 1286 patients transplanted between 1979 and 2009 who survived for 100 days or more. We diagnosed 53 cases of BO. The cumulative incidence was 2.9% in 1 year and 3.7% in 3 years. Among patients with chronic GVHD, the cumulative incidence at the same intervals was 8.4% and 9.9%, respectively. The median time between transplantation and diagnosis of BO was 260 days (49-3877 days). In the multivariate analysis the risk factors for BO were female donor, older recipients and acute GVHD. The main prognostic factor was the severity of pulmonary impairment. Patients who developed BO earlier than 260 days had a worse prognosis than those who did so later. At least 80% of deaths were directly related to BO.
Asunto(s)
Bronquiolitis Obliterante/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Aloinjertos , Brasil/epidemiología , Bronquiolitis Obliterante/epidemiología , Bronquiolitis Obliterante/mortalidad , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) is the only known cure for patients with Fanconi anemia (FA) who develop aplasia or leukemia. However, transplant regimens typically contain high-dose alkylators, which are poorly tolerated in FA patients. Furthermore, as many patients lack human leukocyte antigen (HLA)-matched family donors, alternative donors are used, which can increase the risk of both graft rejection and graft-versus-host disease (GVHD). To improve on these three concerns, we developed a multi-institutional clinical trial using a fludarabine (FLU)-based conditioning regimen with limited alkylators/low-dose radiation, HLA-haploidentical marrow, followed by reduced-dose cyclophosphamide (CY) to treat three FA patients with aplasia. All three patients engrafted with 100% donor CD3 chimerism at 1 month. One patient died early from disseminated toxoplasmosis infection. Of the two survivors, one had significant pretransplant co-morbidities and inadequate immunosuppression, and developed severe acute GVHD. The other patient had only mild acute and no chronic GVHD. With a follow-up of 2 and 3 years, respectively, both patients are doing well, are transfusion-independent, and maintain full donor chimerism. The patient with severe GVHD has resolving oral GVHD and good quality of life. We conclude that using low-intensity conditioning, HLA-haploidentical marrow, and reduced-dose CY for in vivo T-cell depletion can correct life-threatening aplasia in FA patients.
Asunto(s)
Anemia de Fanconi/terapia , Rechazo de Injerto/prevención & control , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Depleción Linfocítica , Linfocitos T/inmunología , Vidarabina/análogos & derivados , Adolescente , Antineoplásicos/uso terapéutico , Niño , Terapia Combinada , Anemia de Fanconi/inmunología , Femenino , Estudios de Seguimiento , Humanos , Quimera por Trasplante/inmunología , Acondicionamiento Pretrasplante , Trasplante Homólogo , Vidarabina/uso terapéuticoRESUMEN
The present work is an epidemiology survey of celiac disease in the province of Terni (Umbria, Italy) in 2002-2010. Data were collected from the Local Health Unit (LHU) 4 (ASL 4), Terni database and were extrapolated from the overall population of 232,540 (as of 2010) by identifying residents with prescription charge exemptions for celiac disease-oriented drugs. Prevalence and incidence analysis over the timeframe being examined showed that prevalence (330 cases in 2010) has consistently been increasing from 2002 to 2010, whereas incidence has remained essentially the same with minor, yearly fluctuations. Both prevalence and incidence were higher in females than in males. Most patients were diagnosed as young adults, with the highest rates in the 10-14, 35-40 and 55-60 age groups. Thus, in the area of investigation, there is evidence for consistent delayed diagnosis, raising the possibility that the atypical form the disease, more difficult to recognize and more likely to escape early diagnosis, may have become increasingly commoner overtime. Because the current prevalence of the disease in the Terni area is estimated to approximate 1%, the anticipated number of cases should amount to 2325, which value contrasts with the currently reported 330 diagnoses. It is suggested that the current illness-defining criteria should be revised so to implement early diagnosis and improve the patients' quality of life and access to treatment.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Indicadores de Salud , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Áreas de Influencia de Salud , Niño , Preescolar , Estudios Epidemiológicos , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
Bernard-Soulier Syndrome (BSS) is an inherited recessive bleeding disorder. In some instances, diagnosis might be restricted to routine blood exams, including bleeding time, prothrombin time (PT), and partial thromboplastin time (APTT). Exams such as platelet aggregation, and testing for expression of ristocetin cofactor, or von Willebrand factor may not be commonly performed. This leads to misdiagnosis in a number of patients, which are subsequently treated erroneously. Flow cytometry has been used widely as a tool in the diagnosis of leukemias, lymphomas, and many other immuno-hematological diseases. The purpose of this study was to assess whether flow cytometry could be helpful in the diagnosis of Bernard-Soulier Syndrome in Brazilian patients. For this, we examined a selected group of 15 patients with suspected BSS based on classical diagnosis. We used a panel of antibodies to detect the expression of glycoproteins GPIbalpha, GPIIb, GPIIIa, GPIX, as well as CD9. Abnormalities of GPIb and GPIX were observed in nine of the 15 patients, which included severe reduction of both antigens, of one or the other, or normal levels but weak expression. Strikingly, this abnormality correlated with severely reduced expression of CD9 in all cases. We discuss the implications for flow cytometric diagnosis of BSS.
Asunto(s)
Síndrome de Bernard-Soulier/diagnóstico , Citometría de Flujo/métodos , Adolescente , Adulto , Anticuerpos Monoclonales , Antígenos CD/análisis , Brasil , Niño , Preescolar , Humanos , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Complejo GPIb-IX de Glicoproteína Plaquetaria/análisis , Glicoproteínas de Membrana Plaquetaria/análisis , Tetraspanina 29 , Adulto JovenRESUMEN
Fanconi anemia is a rare hereditary disease showing genetic heterogeneity due to a variety of mutations in genes involved in DNA repair pathways, which may lead to different clinical manifestations. Phenotypic variability makes diagnosis difficult based only on clinical manifestations, therefore laboratory tests are necessary. New advances in molecular pathogenesis of this disease led researchers to develop a diagnostic test based on Western blot for FANCD2. The objective of the present study was to determine the efficacy of this method for the diagnosis of 84 Brazilian patients with Fanconi anemia, all of whom tested positive for the diepoxybutane test, and 98 healthy controls. The FANCD2 monoubiquitinated isoform (FANCDS+/FANCD2L-) was not detected in 77 patients (91.7%). In 2 patients (2.4%), there was an absence of both the monoubiquitinated and the non-ubiquitinated proteins (FANCD2S-/FANCD2L-) and 5 patients (5.9%) had both isoforms (FANCD2S+/FANCD2L+). This last phenotype suggests downstream subtypes or mosaicism. All controls were diepoxybutane negative and were also negative on the FANCD2 Western blot. The Western blot for FANCD2 presented a sensitivity of 94% (79/84) and specificity of 100% (98/98). This method was confirmed as an efficient approach to screen Brazilian patients with deleterious mutations on FANCD2 (FANCD2S-/FANCD2L-) or other upstream genes of the FA/BRCA pathway (FANCDS+/FANCD2L-), to confirm the chromosome breakage test and to classify patients according to the level of FA/BRCA pathway defects. However, patients showing both FANCD2 isoforms (FANCD2S+/FANCD2L+) require additional studies to confirm mutations on downstream Fanconi anemia genes or the presence of mosaicism.
Asunto(s)
Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/análisis , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Anemia de Fanconi/diagnóstico , Adolescente , Adulto , Western Blotting , Estudios de Casos y Controles , Niño , Preescolar , Rotura Cromosómica , Compuestos Epoxi , Anemia de Fanconi/genética , Femenino , Marcadores Genéticos/genética , Humanos , Masculino , Fenotipo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Fanconi anemia is a rare hereditary disease showing genetic heterogeneity due to a variety of mutations in genes involved in DNA repair pathways, which may lead to different clinical manifestations. Phenotypic variability makes diagnosis difficult based only on clinical manifestations, therefore laboratory tests are necessary. New advances in molecular pathogenesis of this disease led researchers to develop a diagnostic test based on Western blot for FANCD2. The objective of the present study was to determine the efficacy of this method for the diagnosis of 84 Brazilian patients with Fanconi anemia, all of whom tested positive for the diepoxybutane test, and 98 healthy controls. The FANCD2 monoubiquitinated isoform (FANCDS+/FANCD2L-) was not detected in 77 patients (91.7 percent). In 2 patients (2.4 percent), there was an absence of both the monoubiquitinated and the non-ubiquitinated proteins (FANCD2S-/FANCD2L-) and 5 patients (5.9 percent) had both isoforms (FANCD2S+/FANCD2L+). This last phenotype suggests downstream subtypes or mosaicism. All controls were diepoxybutane negative and were also negative on the FANCD2 Western blot. The Western blot for FANCD2 presented a sensitivity of 94 percent (79/84) and specificity of 100 percent (98/98). This method was confirmed as an efficient approach to screen Brazilian patients with deleterious mutations on FANCD2 (FANCD2S-/FANCD2L-) or other upstream genes of the FA/BRCA pathway (FANCDS+/FANCD2L-), to confirm the chromosome breakage test and to classify patients according to the level of FA/BRCA pathway defects. However, patients showing both FANCD2 isoforms (FANCD2S+/FANCD2L+) require additional studies to confirm mutations on downstream Fanconi anemia genes or the presence of mosaicism.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven , /análisis , /genética , Anemia de Fanconi/diagnóstico , Western Blotting , Estudios de Casos y Controles , Rotura Cromosómica , Compuestos Epoxi , Anemia de Fanconi/genética , Marcadores Genéticos/genética , Fenotipo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
In tunnel construction workers, occupational exposure to dust (alpha-quartz and other particles from blasting), gases (nitrogen dioxide, NO(2)), diesel exhausts, and oil mist has been associated with lung function decline, induction of inflammatory reactions in the lungs with release of mediators that may influence blood coagulation, and increased risk of chronic obstructive pulmonary disease. The present molecular epidemiology study was designed to evaluate whether occupational exposure to indoor pollutants during road tunnel construction might result in genotoxic effects. A study group of 39 underground workers and a reference group of 34 unexposed subjects were examined. Primary and oxidative DNA damage, sister-chromatid exchanges (SCE), and micronuclei (MN) were measured in peripheral blood cells. The possible influences of polymorphisms in gene encoding for CYP1A1 and GSTM1 xenobiotic-metabolizing enzymes were also investigated. Exposure assessment was performed with detailed interviews and questionnaires. There were no significant differences in the level of primary and oxidative DNA damage and frequency of SCE between the tunnel workers and controls, whereas the frequency of MN showed a significant increase in exposed subjects compared to controls. No effects of CYP1A1 or GSTM1 variants were observed for the analyzed biomarkers. Since MN in peripheral blood lymphocytes are recognized as a predictive biomarker of cancer risk within a population of healthy subjects, the genotoxic risk of occupational exposure to various indoor environmental pollutants during road tunnel construction cannot be excluded by this biomonitoring study.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Citocromo P-450 CYP1A1/genética , Daño del ADN/efectos de los fármacos , Glutatión Transferasa/genética , Exposición Profesional/efectos adversos , Polimorfismo Genético , Cuarzo/efectos adversos , Intercambio de Cromátides Hermanas/efectos de los fármacos , Transportes , Adulto , Contaminantes Ocupacionales del Aire/sangre , Estudios de Casos y Controles , Ensayo Cometa/métodos , Citocromo P-450 CYP1A1/efectos de los fármacos , Polvo , Glutatión Transferasa/efectos de los fármacos , Humanos , Italia , Masculino , Pruebas de Micronúcleos/métodos , Encuestas y CuestionariosRESUMEN
Imatinib mesylate (IM) is now first-line treatment for CML. To study the results of treatment with IM after IFN failure/intolerance versus allogeneic BMT (allo-BMT), we retrospectively analyzed 264 patients treated for CML in first chronic phase in three different institutions. Over a 6-year period (2001-2006), 174 patients received IM after failure of or intolerance to IFN. During the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). The IM group was older (41 versus 33 years, P<0.001). Five-year EFS was 62% among patients receiving IM and 52% among patients undergoing allo-BMT (P=0.0002). OS at 5 years was 93% for IM-treated patients and 59% for patients undergoing allo-BMT (P<0.0001). Allo-BMT cannot be considered as first-line treatment for CML patients in first chronic phase.
Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/terapia , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Benzamidas , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Mesilato de Imatinib , Masculino , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Adulto JovenRESUMEN
BACKGROUND: Central nervous system fungal infections (FI) are important complications and a cause of mortality in patients who receive hematopoietic stem cell transplantation (HSCT). AIMS: To study the clinical aspects of fungal encephalitis (FE). SETTINGS AND DESIGN: The study was carried out at the HSCT Center of the Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil. MATERIALS AND METHODS: Clinical records and autopsy reports from patients submitted to HSCT with a diagnosis of FE. RESULTS: Twelve patients were diagnosed with FE presenting with lowered level of consciousness, hemiparesis and seizures. We were able to identify two subgroups regarding susceptibility to FE: (1) patients with early onset FI and severe leucopenia, and (2) patients with later onset FI with graft-versus-host disease using immunosuppressive drugs. Eleven of the patients died directly due to the neurological complication, all had post-mortem confirmation of the diagnosis of FI. CONCLUSIONS: These clinical, paraclinical and temporal patterns may provide the opportunity for earlier diagnosis and interventions.
Asunto(s)
Infecciones Fúngicas del Sistema Nervioso Central/etiología , Encefalitis/complicaciones , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Brasil , Infecciones Fúngicas del Sistema Nervioso Central/complicaciones , Infecciones Fúngicas del Sistema Nervioso Central/inmunología , Niño , Preescolar , Encefalitis/inmunología , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Deregulated apoptosis might be involved in some of the features of Fanconi anaemia (FA). The possibility that the pro-apoptotic Bax protein could be involved in an increased susceptibility to apoptosis in FA patients was investigated. MATERIALS AND METHODS: Intracellular Bax expression, Bcl-2 expression (an anti-apoptotic protein) and cell death were analysed in 26 FA peripheral blood lymphocyte samples. RESULTS: Most FA samples (69%) displayed increased levels of Bax and were more susceptible to both spontaneous apoptosis and mitogen activation-induced cell death. Two subgroups were identified: one presented elevated levels of Bax (n = 18), whereas the other (n = 8), had Bax levels lower than controls. Two subgroups based on Bcl-2 expression were also identified: one with normal and another with high Bcl-2 expression. No inverse correlation was found between Bcl-2 levels and Bax expression. A clear difference in susceptibility to induced cell death could be observed between control and FA samples. The best correlation was observed between high levels of Bax and mitogen-induced apoptosis of cells; these displayed characteristics of necrosis secondary to apoptosis, suggesting that the intrinsic apoptotic pathway was being activated. CONCLUSION: Despite increased susceptibility to cell death induction, there was no correlation between Bax levels, chromosome breakage, haematological parameters or androgen therapy. The importance of apoptosis and Bax expression in the clinical development of FA awaits clarification.
Asunto(s)
Apoptosis , Anemia de Fanconi/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Adolescente , Adulto , Células Cultivadas , Niño , Preescolar , Anemia de Fanconi/sangre , Anemia de Fanconi/patología , Humanos , Linfocitos/metabolismo , Linfocitos/patología , Proteína X Asociada a bcl-2/sangreRESUMEN
The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.
Asunto(s)
Bacteriemia/mortalidad , Resistencia a Múltiples Medicamentos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Brasil/epidemiología , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Niño , Preescolar , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de RiesgoRESUMEN
We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51%) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at approximately 8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with < 25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.
Asunto(s)
Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/análisis , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Análisis Multivariante , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodos , Resultado del TratamientoRESUMEN
We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51 percent) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23 percent of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38 percent at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Enfermedad Crónica , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/prevención & control , Prueba de Histocompatibilidad , Antígenos HLA/análisis , Inmunosupresores/uso terapéutico , Análisis Multivariante , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodosRESUMEN
Basiliximab is a chimeric monoclonal antibody that binds to the alpha chain of IL-2R on activated cytotoxic T-cells, inhibiting lymphocyte proliferation. We report 34 patients with refractory acute GVHD (grade III-IV) who received basiliximab from December 1998 to October 2003. Adults received 40 mg weekly (2-3 doses) and children received half of this dose. Median age was 13 years. Twenty-five donors were unrelated. The stem cell source was bone marrow in 30 and cord blood in four. Complete responses were seen in 27/32 patients (84%) with skin, 12/25 (48%) with gut and 6/23 (26%) with liver GVHD. Median duration of response was 38 days (5-1103). Overall survival at 5 years was 20%. Eleven patients (32%) are alive. The main causes of death were CMV (n=4), fungus (n=6), sepsis (n=8), hemorrhage (n=2), and relapse (n=2). Graft-versus-host disease flares were observed in 14 patients (41%), half being rescued by other therapies. In conclusion, basiliximab was able to induce complete responses in patients with refractory acute GVHD. Prospective studies are necessary to evaluate the optimal treatment schedule.