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BACKGROUND: Invasive fungal infections (IFIs) are a major cause of mortality among allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Thanks to the widespread use of secondary antifungal prophylaxis (SAP), a history of IFI is not an absolute contraindication to allo-HSCT. However, IFI recurrence remains a risk factor for transplant-related mortality. METHODS: To evaluate the risk factors for IFI recurrence in allo-HSCT patients receiving SAP, we performed a retrospective analysis of 90 individuals treated at our hospital. SAP antifungal agents included fluconazole (n = 28), voriconazole (n = 25), itraconazole (n = 23), caspofungin (n = 7), and micafungin (n = 7). RESULTS: By day +100, recurrent IFI had occurred in 23 (25.5%) patients. Our multivariate analysis identified 4 factors significantly associated with a risk of IFI recurrence within 100 days of allo-HSCT: duration of neutropenia >18 days, presence of severe acute graft-versus-host disease (aGVHD), <70-day interval between previous infection and transplantation, and use of a narrow-spectrum SAP agent (P = 0.008, 0.010, 0.041, and 0.001, respectively). Of the 87 patients who remained in the study for the duration of the follow-up period (median length: 551 days), 26 (29.9%) died; only 7 (8.0%) of these deaths resulted from a severe fungal infection. CONCLUSION: These results suggest that transplantation outcome can be improved by adequate antifungal treatment before transplantation, better prevention of, and therapy for, severe aGVHD, use of granulocyte colony-stimulating factor to reduce the duration of neutropenia, and use of broad-spectrum prophylaxis agents.
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Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Masculino , Micosis/tratamiento farmacológico , Micosis/prevención & control , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversosRESUMEN
As of 1981, allogeneic bone marrow transplantation (allo-BMT) was applied in an acute leukaemia patient with success. Since then, the number of BMT has been increasing gradually, especially since the 1990s. Approximately 2000 BMTs per year have been performed in recent years in more than 100 BMT units in mainland China. A recent survey of 12 major BMT units indicates that the predominant types of transplantation performed are identical sibling (38.6%), related mismatched/haploidentical (19.4%), unrelated (17.2%), and autologous (24.5%). The indications of major disease entities are acute myeloid leukaemia (32.8%), acute lymphoblastic leukaemia (20%), chronic myeloid leukaemia (CML) [18.9%], and lymphoid malignancy (13.5%). The number of transplants from unrelated donor or related mismatched/haploidentical donor has been increasing significantly in recent 6 years. Granulocyte colony-stimulating factor-mobilised bone marrow plus peripheral blood are routinely used as a source of stem cells for haploidentical BMT. Umbilical cord blood is used less often. Although the total number of patients who received allo-BMT continues to increase, the increase in BMT for CML has been flattened since 2004. By the end of 2008, more than 960 000 volunteer's human leukocyte antigen (HLA) data are available in Chinese Marrow Donor Program (CMDP), and more than 1100 stem cell donations have been performed from it. Stem cells for unrelated BMT in mainland China are mainly from Taiwan Tzu Chi Stem Cell Center and CMDP. Related HLA-mismatched/haploidentical BMT has reached fairly good outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality, disease-free survival, and overall survival, which are comparable with HLA-identical-sibling BMT in the author's BMT units. Syngeneic BMT started successfully in 1964 and has still very good outcomes in more than 23 BMT units from the statistics of Chinese Society of Blood and Marrow Transplantation.
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Trasplante de Médula Ósea/tendencias , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/etnología , China , Trasplante de Células Madre de Sangre del Cordón Umbilical/tendencias , Enfermedad Injerto contra Huésped/prevención & control , Prueba de Histocompatibilidad , Humanos , Trasplante Isogénico/tendenciasRESUMEN
Human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplants (haplo-BMT) from family donors have been intensively studied because of the decreasing family size in mainland China, and also because the Chinese Marrow Donor Program is still not big enough. The protocol for unmanipulated haplo-BMT has been designated as 'GIAC' by Dr DP Lu--'G' represents granulocyte colony-stimulating factor mobilisation; 'I' stands for immunosuppression during pre-conditioning being prolonged and intensified; 'A' stands for the use of antithymocyte globulin; 'C' means combined use of bone marrow and peripheral blood as the graft. Haplo-BMT with GIAC regimen has been shown to be feasible for many applications as reported in 2004. Under this protocol, haplo-BMT has achieved comparable outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality (TRM), disease-free survival (DFS), and overall survival with HLA-identical sibling transplantation. The probabilities of DFS at 2 years in haplo-BMT setting were 70.7%, 49.6%, 22.2% in standard-risk, high-risk, advanced disease groups, respectively. As the third party cells, cord blood co-infusion could significantly reduce the incidence and severity of acute GVHD, and also 100-day TRM. The majority of refractory cytomegalovirus, Epstein-Barr virus and aspergillus infections can be controlled by adoptive cellular therapy. Many patients who early relapsed after BMT and failed, or are ineligible for standard therapy, have been salvaged with dendritic cell-primed cytokine-induced killer cells. With these new strategies, the lower TRM and improved DFS have been attained. Therefore, it is better to consider haplo-BMT for the patients with otherwise incurable haematological malignancies at earlier stage, when matched sibling or unrelated donors are not available.
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Trasplante de Médula Ósea/métodos , Haplotipos , Acondicionamiento Pretrasplante , China , Trasplante de Células Madre de Sangre del Cordón Umbilical , Supervivencia sin Enfermedad , Familia , Supervivencia de Injerto , Humanos , Trasplante de Células Madre de Sangre Periférica , Trasplante Homólogo/métodosRESUMEN
Syngeneic BMT was first performed successfully in China in 1964. In 1981, allogeneic BMT was applied in an acute leukemia patient with success. Since then, the number of BMTs has been increasing gradually, especially since the 1990s. More than 2000 stem cell transplants per year have been performed in recent years in more than 50 BMT units in mainland China. A survey of 16 BMT units from 1986 to 2005 indicates that the predominant types of transplantation performed are identical sibling (36%), related mismatched/haploidentical (11.2%), unrelated (7.5%) and autologous (44.5%) and that the distribution of disease entities and prevalent diseases being transplanted are AML (31%), ALL (16.1%), CML (19.1%) and lymphoid malignancy (22.2%). The number of transplants from unrelated donor or related mismatched/haploidentical donor has increased significantly in the past 5 years. BM and G-CSF-mobilized peripheral blood are used about equally often as a source of hematopoietic stem cells, or they are used in combination. Umbilical cord blood is used least often. Leukemias for allogeneic and lymphoid malignancies for autologous BMT continue to increase, but the increase in BMT for CML has been slow since 2004. By the end of 2007, HLA data were available on more than 700,000 individuals in the Chinese Marrow Donor Program, and 800 stem cell donations have been carried out from these. Related HLA-mismatched/haploidentical BMT has achieved comparable outcomes in terms of severe acute GVHD, chronic GVHD, relapse, treatment-related mortality, disease-free survival (DFS) and overall survival (OS) with HLA-identical sibling transplantation in the author's two BMT units. Cord blood co-infusion as the third-party cells could significantly reduce the incidence and severity of acute GVHD, steroid-refractory acute GVHD and extensive chronic GVHD without an increase in leukemia relapse and could improve DFS and OS.
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Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre del Cordón Umbilical , Bancos de Sangre , China , Sangre Fetal , Enfermedad Injerto contra Huésped/etiología , Haplotipos , Prueba de Histocompatibilidad , HumanosRESUMEN
Chemical and topological parameters have been widely used for predicting the phase selection in high-entropy alloys (HEAs). Nevertheless, previous studies could be faulted due to the small number of available data points, the negligence of kinetic effects, and the insensitivity to small compositional changes. Here in this work, 92 TiZrHfM, TiZrHfMM, TiZrHfMMM (M = Fe, Cr, V, Nb, Al, Ag, Cu, Ni) HEAs were prepared by melt spinning, to build a reliable and sufficiently large material database to inspect the robustness of previously established parameters. Modification of atomic radii by considering the change of local electronic environment in alloys, was critically found out to be superior in distinguishing the formation of amorphous and crystalline alloys, when compared to using atomic radii of pure elements in topological parameters. Moreover, crystal structures of alloying element were found to play an important role in the amorphous phase formation, which was then attributed to how alloying hexagonal-close-packed elements and face-centered-cubic or body-centered-cubic elements can affect the mixing enthalpy. Findings from this work not only provide parametric studies for HEAs with new and important perspectives, but also reveal possibly a hidden connection among some important concepts in various fields.
RESUMEN
Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: â Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . â¡ With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. â¢Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR(1)-AML. Conclusion: MRD positive pre-conditioning was the only negative impact factor for patients with CR(1)-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR(1)-AML after allo-HSCT.
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Neoplasia Residual , Enfermedad Crónica , Citometría de Flujo , Trasplante de Células Madre Hematopoyéticas , Humanos , Factor de Impacto de la Revista , Leucemia Mieloide Aguda , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Trasplante HomólogoRESUMEN
Objective: To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) . Methods: Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively. Results: With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor. Conclusions: Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.
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Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Enfermedad Crónica , Humanos , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.
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Antígenos CD19/inmunología , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Especificidad del Receptor de Antígeno de Linfocitos T/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adolescente , Adulto , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Xenoinjertos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Masculino , Ratones , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Recurrencia , Especificidad del Receptor de Antígeno de Linfocitos T/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: â With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. â¡Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . â¢Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.
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Leucemia Mieloide Aguda , Enfermedad Crónica , Citometría de Flujo , Trasplante de Células Madre Hematopoyéticas , Humanos , Factor de Impacto de la Revista , Pronóstico , Recurrencia , Estudios Retrospectivos , Riesgo , Donantes de Tejidos , Trasplante HomólogoRESUMEN
Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.
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Haplotipos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Donantes de Sangre , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T , Factores de Tiempo , Quimera por Trasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, serum levels of TNFalpha were assessed by ELISA in 243 sera samples from 40 patients who had undergone allogeneic bone marrow transplantation (BMT). Serum TNFalpha levels were measured before BMT and at different time points after BMT. The results were correlated with acute GVHD (aGVHD), infection and conditioning regimen. Serum TNFalpha levels were significantly higher in patients with grades II-IV aGVHD than in those with grade 0 or I aGVHD, but there was no clear correlation between serum TNFalpha and severity of aGVHD. Serum TNFalpha levels in infected patients were not statistically different from those in patients without infection. The conditioning regimen did not cause a significant rise in TNFalpha levels. These results indicate that TNFalpha may be useful for the diagnosis of aGVHD and for differentiating between aGVHD and other BMT-related complications, such as infection.
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Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/sangre , Factor de Necrosis Tumoral alfa/análisis , Enfermedad Aguda , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Acondicionamiento PretrasplanteRESUMEN
A patient with severe aplastic anaemia achieved restoration of marrow function following marrow transplantation from her identical twin. Sixteen years later both patient and donor are in good health without significant haematologic abnormality. This is the first case of successful syngeneic marrow transplantation reported in China. The success of this procedure, without immunosuppression, suggests that this patient's disease was due to a defect in haemopoietic stem cells rather than in marrow microenvironment. A review of the 23 other patients treated by syngeneic marrow transplantation for aplastic anaemia suggests that approximately one-half have a disease due primarily to a defect in stem cells. Conversely for a patient who does not recover haemopoiesis after syngeneic marrow transplantation a further transplant preceded by immunosuppressive therapy may be curative. No direct correlation between the number of syngeneic marrow cells transfused and the success of the graft can be discerned from the literature.
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Anemia Aplásica/terapia , Trasplante de Médula Ósea , Adulto , Femenino , Hematopoyesis , Humanos , Recuento de Plaquetas , Embarazo , Gemelos MonocigóticosRESUMEN
Bone marrow transplantation, both allogeneic and autologous, has been undertaken in People's Republic of China (PRC) since the beginning of 1980s at a steadily increasing rate. Eight BMT units can be regarded as active. Altogether 230 cases of allogeneic- and syngeneic-BMT have been reported to the Chinese BMT Registry (CBMTR) by the end of October 1993. More than 85% of the cases were acute or chronic leukemia. The incidence of acute grade II-IV GVHD was 29.5% in matched sibling BMT. The special problems of BMT in China include decreasing family size, financial difficulties and relatively high incidence of various viral infections. A number of unique approaches to treatment have been tested with benefit including mixed infusion of fetal cells for prophylaxis of acute GVHD and intravenous placental globulin for the treatment of chronic GVHD. Garlic ingredient has been shown to be effective against CMV and has been used in the clinic with encouraging results. The overall outcome of allogeneic and autologous BMT are comparable to those in the other major BMT centers in the world.
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Trasplante de Médula Ósea , China/epidemiología , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Incidencia , Sistema de Registros , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The first cooperative study of the Asian Pacific bone marrow transplantation group included 75 patients with early leukemia who received human leukocyte antigen-matched sibling bone marrow transplants and were randomized into granulocyte colony-stimulating factor and control groups. The selected patients were registered from 10 centers in six countries and areas within Asia (Beijing, Taipei, Hong Kong, Japan, Korea, and Malaysia). The incidence of grades II-IV acute graft-vs.-host disease was 22.2%, and the 2-year survival rate was 62.7%. The period of protective isolation (27.1-66.7 days), period of hospitalization (38.6-130.5 days), and medical costs for 4 months (US $10,300-US $80,803) varied considerably. Good cooperation, i.e., low rate of protocol violation or rapid and precise presentation of case reports, was obtained.
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Trasplante de Médula Ósea , Leucemia/terapia , Costos y Análisis de Costo , Humanos , Leucemia/economía , Leucemia/fisiopatología , Calidad de Vida , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Amylose reacted in N,N-dimethylformamide with crystalline bromomethylenedimethylammonium bromide (Vilsmeier bromide) to give 6-bromo-6-deoxyamylose with a high degree of substitution. Reduction of the bromoamylose with sodium borohydride yielded 6-deoxyamylose that, following controlled acetolysis, gave 6-deoxymaltooligosaccharides. Such oligosaccharides, of appropriate chain-length, formed stable complexes with long-chain fatty acids that have a dissociation constant of about 2 microM in their interaction with parinaric acid (trans-9,11,13,15-octadecatetraenoic acid). Treatment of 6-bromoamylose with sodium methoxide in dimethyl sulfoxide produced a 3,6-anhydroamylose that contains few unaltered D-glucose units. This anhydroamylose also bound to a palmitoyl-resin column, suggesting that the polymer may be partially helical and somewhat lipophylic. Finally, reaction of 6-bromoamylose with methylvinyl ether led to the 2,3-di(methoxyethyl) ether that, on reaction with sodium methoxide, gave the 6-methyl ether from which 6-O-methylamylose was obtained by mild acid hydrolysis.
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Ácidos Grasos Insaturados , Maltosa/análogos & derivados , Oligosacáridos , Colorantes Fluorescentes , Indicadores y Reactivos , Maltosa/síntesis química , Oligosacáridos/síntesis química , Relación Estructura-ActividadRESUMEN
In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), we have examined the effect of PGG in vitro and in a model of the xenogeneic, local graft-versus-host reaction (LGVHR). PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P less than 0.005) and depressed interleukin-2 (IL-2) levels in such cultures at 72 hours (P less than 0.01). In contrast phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced T and B lymphocyte blastogenesis was not affected by such PGG treatment. PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability. Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation. An immunosuppressive effect of PGG on the LGVHR was tested in a model of intracutaneous transplantation of PGG-treated human lymphocytes into cyclophosphamide-immunosuppressed rats. Lymphoprep-separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing: (1)PGG, 4 mg/ml, (2) human plasma albumin, 4 mg/ml, (3) mitomycin-C, 25 micrograms/ml, or (4) no additive. Cells of each preparation (3 X 10(7) cells in 0.1 ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells, each rat received [125I]UdR (10 muCi) intraperitoneally and was killed after 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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Reacción Injerto-Huésped , Inmunosupresores , Placenta/análisis , gammaglobulinas/inmunología , Animales , División Celular , Interleucina-2/metabolismo , Linfocitos/inmunología , Masculino , Ratas , Ratas Endogámicas , gammaglobulinas/farmacologíaRESUMEN
The in vitro anti-viral activity of garlic extract (GE) on human cytomegalovirus (HCMV) was evaluated by tissue culture, plaque reduction and early antigen assay. A dose dependent inhibitory effect of GE was evident when GE was applied simultaneously with HCMV. But the effect was stronger when the monolayers were pretreated with GE. In addition, the anti-viral effect of GE persisted long in infected cells after its being removed from the culture medium. The strongest anti-viral effect of GE was demonstrated when it was applied continuously. It is therefore recommended that clinical use of GE against HCMV infection should be persistent and the prophylactic use of GE is preferable in immunocompromised patients.
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Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Ajo , Plantas Medicinales , Humanos , Extractos Vegetales/farmacología , Ensayo de Placa ViralRESUMEN
Eighteen patients with leukemia have received HLA-identical allogeneic bone marrow transplantation (BMT) at our hospital since 1981. Fifteen of these patients have been living without relapse. for prophylaxis of GVHD, MTX was used in 8 patients, and cyclosporine (CSP) together with MTX in 6 patients, 3 received multiple agents at much smaller dosage, including monoclonal antibody. All patients received intravenous placental gamma-globulin, and 16 received garlic extract. Three patients died. One, who neither received MTX, nor CSP died of hyperacute GVHD, one who did not receive garlic extract died of GMV pneumonia, and the third one died of tuberculosis 18 months after BMT.
Asunto(s)
Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Trasplante HomólogoRESUMEN
Despite their long histories, acupuncture and hypnosis have only recently been acknowledged as valuable by the medical establishment in the U.S. Few studies have used rigorous prospective measurement to evaluate the individual or relative merits of hypnosis and acupuncture in specific clinical settings. In this study, 25 patients with various head and neck pain were studied. Each had an initial assessment of their pain, as well as of their attitudes and expectations. All patients received acupuncture, followed by a reassessment of their pain. After a washout period they received another assessment of pain before and after hypnosis therapy. Preferences for therapy were sought following the hypnotic intervention. Both acupuncture and hypnosis were effective at relieving pain under these conditions. The average relief in pain reported was 4.2 units on a ten point scale, with hypnosis reducing pain by a mean of 4.8 units, compared to 3.7 for acupuncture (p = 0.26). Patient characteristics appeared to impact the effectiveness of treatment: patients with acute pain benefited most from acupuncture treatment, whereas patients with psychogenic pain were more likely to benefit from hypnosis. Patients with chronic pain had more variation in their results. Patients who received healing suggestions from a tape during a hypnotic trance benefited more than those who received no such suggestion, and acupuncture patients who were needle phobic benefited less than those who were not fearful of needles. This study demonstrates the benefits of well designed studies of the effectiveness of these alternative modalities. More work is needed to help practitioners identify which patients are most likely to benefit from these complementary therapies.
Asunto(s)
Terapia por Acupuntura , Dolor Facial/terapia , Hipnosis , Dolor de Cuello/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Resultado del TratamientoRESUMEN
Intravenous placental immunoglobulin (IV Pt IG) was used for the treatment of chronic graft versus host disease (CGVHD) in 30 patients who are refractory to steroid and cyclosporinic A. 15 (50%) patients showed excellent response and 11 (36.66%) good response. The total response rate is 86.66%. The dosage of IV Pt IG was 4 gm/day in adults by intravenous infusion. Effectiveness of IV PtIG was discerned within 2 weeks. The plasma levels of IgG, IgA and IgM were tested before and after IV PtIG treatment. There was no significant statistical difference between the plasma IgG, IgA, IgM levels in pre- and post-treatment period. The efficacy of IV PtIG against CGVHD is therefore ascribed to its pharmacological effect.