RESUMEN
Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified. As there are no data to confirm the mechanism of PIR, we used a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system to identify a specific marker for PIR. The protein expression profile of serum samples from CBT patients was analyzed with a SELDI-TOF MS system. A protein peak that commonly predominated in PIR was purified by an anion exchange column, isolated by SDS-PAGE, and identified by in-gel trypsin digestion, and mass fingerprinting. A 8.6-kDa protein and 11-kDa protein that increased by 10- to 100-fold in the serum of patients during PIR was identified as anaphylatoxin C4a and serum amyloid A. SELDI-TOF MS system in combination with other proteomic methods could serve as a potential diagnostic tool in discovering biomarkers for PIR after CBT.
Asunto(s)
Proteínas Sanguíneas/biosíntesis , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adulto , Anciano , Biomarcadores/análisis , Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/inmunología , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/inmunología , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Glucemia/metabolismo , Enfermedad Injerto contra Huésped/prevención & control , Insulina/metabolismo , Trasplante de Células Madre/efectos adversos , Tacrolimus/uso terapéutico , Adulto , Anciano , Homeostasis , Humanos , Hipoglucemiantes/uso terapéutico , Inmunosupresores/uso terapéutico , Insulina/inmunología , Resistencia a la Insulina , Secreción de Insulina , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Some studies have shown that intensive glucose control (IGC) improves outcome in the intensive care unit setting. However, it is the benefit of IGC in hematopoietic SCT (HSCT) that is not well defined. Between June 2006 and May 2007, IGC was maintained prospectively after allogeneic HSCT and clinical outcomes were compared with a cohort matched for conditioning regimen, source of stem cells, age and relation to donor. A stratified Cox regression model was used. There were no significant differences in baseline clinical characteristics. The median age was 43.5 years in both groups. The primary diagnosis was a hematologic malignancy. Patients in the IGC group had a lower glucose level (least-square mean, 116.4 vs 146.8 mg per 100 ml, P<0.001) compared to the standard glucose control group. The incidences of documented infections and bacteremia were significantly lower in the IGC group (14 vs 46%, P=0.004, 9 vs 39%, P=0.002, respectively). IGC tended to reduce the incidence of renal dysfunction (19 vs 37%, P=0.36) and the elevation of C-reactive protein (18 vs 38%, P=0.13). This study suggests that IGC has may have a beneficial effect after HSCT. IGC should be evaluated further in a large prospective, randomized study.
Asunto(s)
Glucemia/análisis , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II-IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration-time curve of the first administration remained at less than 1500 micromol min/l in 27 of the 29 patients (93%), and between 900 and 1350 micromol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.
Asunto(s)
Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped , Granulocitos/citología , Humanos , Japón , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Valpha24(+) natural killer T (NKT) cell is a human counterpart of mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired potential antitumor activity. The efficient expansion of NKT cells is an obstacle to the clinical application of Valpha24(+) NKT cells for immunotherapy. METHODS: We used mononuclear cells (MNC) obtained from the peripheral blood (PB) of normal healthy donor (HD) and malignant lymphoma (ML) patients before and after granulocyte colony-stimulating factor (G-CSF) treatment. MNC were cultured for 12 days with alpha-galactosylceramide (100 ng/mL) and interleukin-2 (IL-2; 100 U/mL). RESULTS: The fold expansion of Valpha24(+) NKT cells was higher in HD than in ML patients (208 versus 0.00), despite comparable numbers of Valpha24(+) NKT cells before culture. G-CSF administration enhanced the predominance of Valpha24(+) NKT cell fold expansion in HD compared with ML patients (1935 versus 1.95). After treatment with G-CSF, the expression of CD1d molecules was up-regulated in CD14(+) cells from HD but not ML patients. The fold expansion of Valpha24(+) NKT cells and CD1d expression on CD14(+) cells was strongly correlated in both HD and ML patients (r(2)=0.84). However, replacement of a patient's CD14(+) cells with HD cells did not increase the efficacy of Valpha24(+) NKT cell expansion. DISCUSSION: G-CSF-mobilized PB from ML patients has inhibitory characteristics for Valpha24(+) NKT cell expansion as a result of both monocytes and Valpha24(+) NKT cells. Multiple procedures would be needed for the expansion of patients' Valpha24(+) NKT cells.
Asunto(s)
Antígenos CD1/genética , Inmunoterapia Adoptiva , Células Asesinas Naturales/trasplante , Linfoma/terapia , Adulto , Antígenos CD1/inmunología , Antígenos CD1/metabolismo , Proliferación Celular , Células Cultivadas , Femenino , Galactosilceramidas/farmacología , Regulación Neoplásica de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/inmunología , Humanos , Inmunidad Innata , Inmunofenotipificación , Inyecciones Subcutáneas , Interleucina-2/farmacología , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/trasplante , Receptores de Lipopolisacáridos/biosíntesis , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/inmunología , Linfoma/inmunología , Linfoma/patología , Masculino , Receptores de Antígenos de Linfocitos T/biosíntesis , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Escape del Tumor/genética , Escape del Tumor/inmunologíaRESUMEN
Pancreatic cancer is a frequent cause of cancer-related mortality and has an extremely poor prognosis. To evaluate the efficacy of allogeneic hematopoietic SCT with reduced-intensity conditioning (RICT) against pancreatic cancer, we analyzed the clinical data of 22 patients. After a fludarabine-based conditioning regimen followed by the infusion of PBSCs, all but two achieved engraftment. Complete, partial and minor response was observed in 1, 2 and 2 patients, respectively, with an overall response rate of 23%. Median survival was only 139 days and the major cause of death was tumor progression. Poor performance status before RICT and a lower number of infused CD34-positive cells were associated with shorter survival after RICT. Patients who developed chronic GVHD tended to survive longer than those who did not. These findings support the investigation of a novel treatment strategy to enhance the immunological effect against pancreatic cancer.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias Pancreáticas/terapia , Acondicionamiento Pretrasplante , Adulto , Anciano , Antígeno Carcinoembrionario/análisis , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Trasplante HomólogoAsunto(s)
Neoplasias del Sistema Nervioso Central/secundario , Efecto Injerto vs Tumor , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia Local de Neoplasia/terapia , Sarcoma de Ewing/terapia , Adulto , Neoplasias del Sistema Nervioso Central/terapia , Femenino , Humanos , Sarcoma de Ewing/patología , Hermanos , Trasplante HomólogoRESUMEN
To assess infectious complications associated with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced- and conventional-intensity conditioning regimens (RIC, n=91; CIC, n=54, respectively), we retrospectively analyzed data from 145 consecutive patients with cGVHD after allogeneic HSCT from a human leukocyte antigen-matched related or unrelated donor. In the present retrospective analysis, 57% (83/145) of patients with cGVHD developed infections, with a mortality rate of 27% (22/83). The incidences of bacteremia (n=28), central venous catheter-related infections (n=11), bacterial pneumonia (n=4), invasive aspergillosis (n=7), and adenoviral hemorrhagic cystitis (n=8) were significantly higher in patients with prednisolone dose >or=1 mg/kg at the time of diagnosis of cGVHD. The present results suggest that infections associated with cGVHD, especially after high-dose prednisolone, are predictive of poor outcome regardless of whether the patient received RIC or CIC.
Asunto(s)
Enfermedades Transmisibles , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante , Trasplante Homólogo/efectos adversos , Adolescente , Adulto , Anciano , Aspergilosis/epidemiología , Aspergilosis/microbiología , Bacteriemia/epidemiología , Bacteriemia/microbiología , Busulfano/administración & dosificación , Cateterismo Venoso Central/efectos adversos , Enfermedad Crónica , Enfermedades Transmisibles/complicaciones , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/etiología , Enfermedades Transmisibles/mortalidad , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/microbiología , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal TotalRESUMEN
In order to evaluate whether we could predict reactivation of CMV by monitoring the number of CMV-specific cytotoxic T-lymphocytes (CTL), tetramer analysis was performed in 37 patients who underwent hematopoietic stem cell transplantation (HSCT). The results disclosed that the mean number of CMV-specific CTL at day 30 did not differ among patients who developed CMV antigenemia (22/microl) and those who did not (12/microl). Serial tetramer analysis showed that 21% of the patients had >10/microl CMV-specific CTL at the first detection of CMV antigenemia and 67% of the patients had more than 10/microl CMV-specific CTL at the onset of CMV disease. Intracellular staining upon stimulation by CMV lysates and peptide in patients with CMV colitis revealed that both IFN-gamma producing CD4+ and CD8+ lymphocytes were suppressed at the onset of CMV colitis (1.6 and 8/microl), which increased with recovery of the disease (19 and 47/microl). These data suggest that it is difficult to predict CMV reactivation solely by the number of CMV-specific CTL. We suggest that additional functional analysis by intracellular cytokine assay may be useful for immunomonitoring against CMV.
Asunto(s)
Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , Antígenos Virales/sangre , Antígenos Virales/metabolismo , Colitis/virología , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/prevención & control , Epítopos de Linfocito T/inmunología , Antígenos HLA-A/metabolismo , Antígeno HLA-A2 , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Interferón gamma/metabolismo , Recuento de Linfocitos/métodos , Persona de Mediana Edad , Fosfoproteínas , Factores de Riesgo , Factores de Tiempo , Proteínas de la Matriz Viral , Activación ViralAsunto(s)
Infecciones por Citomegalovirus/diagnóstico , Enterocolitis/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Oportunistas/diagnóstico , Adolescente , Adulto , Anciano , Niño , Preescolar , Colonoscopía , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Persona de Mediana EdadRESUMEN
In 56 pediatric and adolescent patients (median age 7 years, range 1-21) with various solid tumors, peripheral blood stem cells (PBSC) were mobilized with granulocyte colony-stimulating factor (G-CSF) alone, and the yields of PBSC and engraftment kinetics following autologous peripheral blood stem cell transplantation (PBSCT) were evaluated retrospectively. Granulocyte colony-stimulating factor (10 microg/kg) was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for 5 days. The peaks of CD34+ cells and colony-forming units-granulocyte/macrophage in the blood were observed on days 4 through 6 of G-CSF administration in all patients. Peripheral blood stem cell harvest was commenced on day 5 of G-CSF treatment. Compared to the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in patients mobilized with G-CSF alone. However, there were no significant differences in WBC and ANC engraftment compared to the chemotherapy plus G-CSF mobilization group. Platelet recovery following autologous PBSCT was delayed in patients mobilized with G-CSF alone. The median time taken for ANC and platelet counts to reach 0.5 x 10(9) and 20 x 10(9)/l was 12 days (range: 9-28) and 15 days (8-55), respectively, in all patients who received PBSC mobilized by G-CSF alone. In summary, mobilization with G-CSF alone can mobilize sufficient CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric and adolescent patients with solid tumors, and even in heavily pre-treated patients.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Neoplasias/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Antígenos CD34/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Lactante , Cinética , Masculino , Neoplasias/diagnóstico , Neoplasias/inmunología , Trasplante de Células Madre de Sangre Periférica/métodos , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
A population pharmacokinetic analysis was performed in 30 patients who received an intravenous busulfan and cyclophosphamide regimen before hematopoietic stem cell transplantation. Each patient received 0.8 mg/kg as a 2 h infusion every 6 h for 16 doses. A total of 690 concentration measurements were analyzed using the nonlinear mixed effect model (NONMEM) program. A one-compartment model with an additive error model as an intraindividual variability including an interoccasion variability (IOV) in clearance (CL) was sufficient to describe the concentration-time profile of busulfan. Actual body weight (ABW) was found to be the determinant for CL and the volume of distribution (V) according to NONMEM analysis. In this limited study, the age (range 7-53 years old; median, 30 years old) had no significant effect on busulfan pharmacokinetics. For a patient weighting 60 kg, the typical CL and V were estimated to be 8.87 l/h and 33.8 l, respectively. The interindividual variability of CL and V were 13.6 and 6.3%, respectively. The IOV (6.6%) in CL was estimated to be less than the intraindividual variability. These results indicate high interpatient and intrapatient consistency of busulfan pharmacokinetics after intravenous administration, which may eliminate the requirement for pharmacokinetic monitoring.
Asunto(s)
Busulfano/farmacocinética , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compartimentos de Líquidos Corporales , Índice de Masa Corporal , Busulfano/administración & dosificación , Niño , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Variaciones Dependientes del Observador , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Poor collection results are a clinical problem in granulocyte-colony stimulating factor (G-CSF)-induced peripheral blood stem cell (PBSC) collection in healthy donors. It would be beneficial to be able to predict the PBSC yield from allogeneic donors before mobilization or harvesting. MATERIALS AND METHODS: We examined the relationship between certain donor characteristics and the effectiveness of G-CSF-induced PBSC collection in 59 healthy family donors aged 3-63 years old (median 16 years). G-CSF was administered subcutaneously at 10 microg/kg for mobilization, daily for 5 days, and PBSC harvest using a continuous blood cell separator was started on day 5 of G-CSF treatment. Total cell yields were calculated as the number per unit of processed blood (l) per unit weight of the donor (kg). RESULTS: In a univariate analysis, the donor's age, body mass index (BMI), white blood cell (WBC) count before mobilization, and platelet count before and during mobilization were significantly correlated with the yield of mononuclear cells (MNC), CD34(+) cells and granulocyte-macrophage colony-forming units (GM-CFU). Younger age (P < 0.001), a low BMI (P = 0.002), a high WBC count before mobilization (P = 0.004), a high platelet count before (P = 0.012) and during (P < 0.05) mobilization, and a low speed of withdrawal (P = 0.019) were associated with a higher CD34(+) cell yield. No significant correlation was found for gender, the type of G-CSF, the serum level of G-CSF, the type of cell separator, or the type of blood access. A multivariate forward and backward stepwise selection regression analysis showed that the factors associated with CD34(+) cell yield were age, platelet count before and during mobilization, and circulating CD34(+) cell concentration on day 2 of G-CSF treatment. CONCLUSION: In this small preliminary study, we found that donor age is the most important factor in predicting G-CSF-induced PBSC yields. Old age and low platelet counts before mobilization might be useful indicators for identifying poor mobilizers. Further validation of these findings in a larger number of donors are needed to establish whether these findings apply to other populations.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Leucaféresis , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
Cytomegalovirus-specific cytotoxic T-lymphocytes (CMV-CTL) are essential for the control of CMV reactivation. To monitor the quantity and function of CMV-CTL after hematopoietic stem cell transplantation (HSCT), two CMV epitopes that bind to HLA-A*0201 NLVPMVATV (A*02NLV) and HLA-A*2402 QYDPVAALF (A*24QYD) were evaluated for their immunological potential. Samples from patients with the HLA-A*02 or HLA-A*24 serotype were analyzed by tetramer, intracellular cytokine staining and enzyme-linked immunospot (ELISPOT) assay. There were significantly more A*02NLV-specific CMV-CTL than A*24QYD (23 x 10(6) vs 0.4 x 10(6)/l). The frequency of IFN-gamma-producing cells was also higher upon stimulation with A*02NLV than with A*24QYD (2.5 vs 0.1%/CD8). Furthermore, the magnitude of CMV-CTL expansion was two- to 50-fold when cells were cultured with A*02NLV, while only an insignificant increase was observed in culture with A*24QYD. Although the number of A*24QYD-specific CMV-CTL was very low in most of the HLA-A*24 patients, the incidence of CMV reactivation did not differ between those with HLA-A*02 and HLA-A*24 serotype alone. These results suggest that an epitope other than A*24QYD plays a major role in patients with HLA-A*24. Our study also showed that A*02NLV may be a useful epitope for monitoring CMV-CTL not only in patients with HLA-A*0201 but also in those with the A*0206 genotype.
Asunto(s)
Citomegalovirus/inmunología , Antígenos HLA-A/inmunología , Trasplante de Células Madre Hematopoyéticas , Neoplasias/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , Antígenos Virales/inmunología , Células Cultivadas , Epítopos de Linfocito T/inmunología , Femenino , Antígeno HLA-A2 , Antígeno HLA-A24 , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Interferón gamma/inmunología , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Neoplasias/virología , Fenotipo , Trasplante Homólogo , Activación Viral/inmunologíaRESUMEN
To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25-2.97; P=0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; P<0.001), risk of underlying diseases (1.85, 1.21-2.83; P=0.004), acute GVHD (2.57, 1.72-3.84; P<0.001), and CML (0.38, 0.21-0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.
Asunto(s)
Neoplasias Hematológicas/terapia , Trasplante de Células Madre , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Leucemia/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/terapia , Recurrencia , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodosRESUMEN
We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12-10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08-20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090-0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped , Efecto Injerto vs Tumor , Humanos , Japón , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Riesgo , Trasplante de Células Madre , Factores de Tiempo , Resultado del TratamientoRESUMEN
Since the introduction of reduced-intensity stem-cell transplantation (RIST), allogeneic stem-cell transplantation has become available for elderly patients. While pharmacokinetics of cyclosporine might differ according to age or other factors, cyclosporine is uniformly started at an oral dose of 6 mg/kg/day. We retrospectively reviewed medical records of 35 patients aged between 32 and 65 (median 52) years who had undergone RIST. Doses of cyclosporine were adjusted to the target blood trough level of 150-250 ng/ml. Cyclosporine dosages were changed in 33 patients (94%). Dose reduction was required in 32 patients because of high blood levels (n=25), renal dysfunction (n=3), hepatic dysfunction (n=2), and hypertension (n=2). Cyclosporine doses were increased in one because of the suboptimal level. The median of the achieved stable doses was 3.1 mg/kg/day (range, 1.0-7.4). Five patients sustained Grade III toxicities according to NCI-CTC version 2.0: renal dysfunction (n=4), hyperbilirubinemia (n=2), and hypertension (n=2). No patients developed grade IV toxicity. There was no statistically significant difference in the frequency and severity of cyclosporine toxicities between patients aged 50 years and above and those below 50 years. The initial oral cyclosporine dose of 6 mg/kg/day was unnecessarily high irrespective of age. The possible overdose of cyclosporine might have aggravated regimen-related toxicities.
Asunto(s)
Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Trasplante de Células Madre/métodos , Administración Oral , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Humanos , Japón , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoAsunto(s)
Lesión Renal Aguda/terapia , Ciclosporina/administración & dosificación , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Diálisis RenalRESUMEN
The prognosis of patients with metastatic retinoblastoma is poor with conventional chemotherapy and radiation. Since retinoblastoma is highly chemosensitive, dose-escalation of chemotherapeutic agents with stem cell support should be promising. We report our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) in patients with metastatic retinoblastoma. Five patients with metastatic retinoblastoma underwent HDC with autologous SCT following conventional chemotherapy and local radiation therapy. Stem cells (bone marrow in four and peripheral blood stem cells in one) were collected after marrow involvement was cleared. Melphalan was a key drug in all patients, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Three patients are currently alive disease-free at 113, 107 and 38 months, respectively, from the time of SCT. They had no central nervous system (CNS) involvement. The two patients who died of disease had CNS involvement. No long-term sequelae of HDC have been noted. Our treatment strategy using HDC appears to be effective for treating metastatic retinoblastoma without CNS involvement.