RESUMEN
Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft-versus-host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37; P=0.002) and lower (5-15 vs 20 mg/kg) ATG dose (hazard ratio=4.55; P=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning.
Asunto(s)
Anemia de Células Falciformes , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anciano , Anemia de Células Falciformes/terapia , Quimerismo , Fertilidad , Francia/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Supervivencia sin Progresión , Hermanos , Acondicionamiento PretrasplanteRESUMEN
Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median follow-up of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Antineoplásicos Alquilantes/uso terapéutico , Trasplante de Médula Ósea/métodos , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Tiotepa/uso terapéutico , Adolescente , Adulto , Antineoplásicos Alquilantes/farmacología , Niño , Ciclofosfamida/farmacología , Femenino , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tiotepa/farmacología , Donantes de Tejidos , Adulto JovenRESUMEN
Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bone marrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/mortalidad , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas/mortalidad , Histocompatibilidad , Humanos , Lactante , Masculino , Hermanos , Encuestas y Cuestionarios , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×108 (range 0.7-75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units.
Asunto(s)
Anemia de Células Falciformes/terapia , Almacenamiento de Sangre/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/normas , Familia , Sangre Fetal/citología , Adolescente , Adulto , Bancos de Sangre/normas , Niño , Preescolar , Femenino , Supervivencia de Injerto , Histocompatibilidad , Humanos , Lactante , Masculino , Embarazo , Hermanos , Tasa de Supervivencia , Donantes de Tejidos , Adulto JovenAsunto(s)
Anemia de Células Falciformes/mortalidad , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad/métodos , Adolescente , Adulto , Factores de Edad , Anemia de Células Falciformes/inmunología , Anemia de Células Falciformes/patología , Anemia de Células Falciformes/terapia , Niño , Preescolar , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Incidencia , Lactante , Masculino , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sß(0)), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 10(9)/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.
Asunto(s)
Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/terapia , Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Enfermedades Arteriales Cerebrales/terapia , Tamizaje Neonatal/métodos , Ultrasonografía Doppler Transcraneal/métodos , Enfermedades Arteriales Cerebrales/congénito , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico por imagen , Enfermedades del Recién Nacido/terapia , Angiografía por Resonancia Magnética/efectos adversos , Angiografía por Resonancia Magnética/métodos , Masculino , Tamizaje Neonatal/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler Transcraneal/efectos adversos , Ultrasonografía Doppler Transcraneal/estadística & datos numéricosRESUMEN
BACKGROUND: The impact of cytogenetic abnormalities in multiple myeloma after allogeneic stem cell transplantation has not been clearly defined. This study examines whether allogeneic stem cell transplantation could be of benefit for myeloma patients with high-risk cytogenetic abnormalities. DESIGN AND METHODS: This is a retrospective multicenter analysis of the registry of the Société Française de Greffe de Moelle et de Thérapie Cellulaire, including 143 myeloma patients transplanted between 1999 and 2008. RESULTS: The incidences of cytogenetic abnormalities were 59% for del(13q), 25% for t(4;14), 25% for del(17p) and 4% for t(14;16). When comparing the population carrying an abnormality to that without the same abnormality, no significant difference was found in progression-free survival, overall survival or progression rate. Patients were grouped according to the presence of any of the poor prognosis cytogenetic abnormalities t(4;14), del(17p) or t(14;16) (n=53) or their absence (n=32). No difference in outcomes was observed between these two groups: the 3-year progression-free survival, overall survival and progression rates were 30% versus 17% (P=0.9), 45% versus 39% (P=0.8) and 53% versus 75% (P=0.9), respectively. CONCLUSIONS: These data indicate that allogeneic stem cell transplantation could potentially be of benefit to high-risk myeloma patients.
Asunto(s)
Aberraciones Cromosómicas , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
This is a translation of the paper "Recommendations for the application and follow-up of quality controls in medical biology laboratories" published in French in the journal Annales de Biologie Clinique (Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.). The recommendations proposed in this document are the result of work conducted jointly by the Network of Accredited Medical Laboratories (LABAC), the French Society of Medical Biology (SFBC) and the Federation of Associations for External Quality Assessment (FAEEQ). The different steps of the implementation of quality controls, based on a risk analysis, are described. The changes of reagent or internal quality control (IQC) materials batches, the action to be taken in case of non-conform IQC results, the choice of external quality assessment (EQA) scheme and interpretation of their results as well as the new issue of analyses performed on several automatic systems available in the same laboratory are discussed. Finally, the concept of measurement uncertainty, the robustness of the methods as well as the specificities of near-patient testing and rapid tests are described. These recommendations cannot apply for all cases we can find in medical laboratories. The implementation of an objective alternative strategy, supported with documented evidence, might be equally considered.
Asunto(s)
Laboratorios/normas , Control de Calidad , HumanosRESUMEN
The Wilms tumor antigen, WT1, is associated with several human cancers, including leukemia. We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I-binding epitope downstream of a foreign sequence of tetanus toxin. Three p.DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2-restricted epitope, induced cytotoxic T lymphocytes (CTLs) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTLs killed human leukemia cells in vitro, indicating peptide processing/presentation. Low numbers of T cells specific for these epitopes have been described in cancer patients. Expanded human T cells specific for each epitope were lytic in vitro. Focusing on human WT1(37-45)-specific cells, the most avid of the murine responses, we demonstrated lysis of primary leukemias, underscoring their clinical relevance. Finally, we showed that these human CTL kill target cells transfected with the relevant p.DOM-peptide DNA vaccine, confirming that WT1-derived epitopes are presented to T cells similarly by tumors and following DNA vaccination. Together, these data link mouse and human studies to suggest that rationally designed DNA vaccines encoding WT1-derived epitopes, particularly WT1(37-45), have the potential to induce/expand functional tumor-specific cytotoxic responses in cancer patients.
Asunto(s)
Linfocitos T/inmunología , Vacunación , Vacunas de ADN/inmunología , Proteínas WT1/inmunología , Animales , Presentación de Antígeno/inmunología , Línea Celular Tumoral , Proliferación Celular , Ensayo de Unidades Formadoras de Colonias , Citotoxicidad Inmunológica , Antígenos HLA-A/inmunología , Antígeno HLA-A2 , Salud , Hematopoyesis , Humanos , Leucemia/patología , Activación de Linfocitos/inmunología , Ratones , Ratones Transgénicos , Péptidos/inmunología , Linfocitos T/citología , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Donantes de TejidosRESUMEN
BACKGROUND: Patients with poor-risk Waldenström's macroglobulinemia have suboptimal response and early post-treatment relapse with conventional therapies. Hence, new therapeutic approaches such as allogeneic stem cell transplantation should be evaluated in these patients. DESIGN AND METHODS: We examined the long-term outcome of allogeneic stem cell transplantation in Waldenström's macroglobulinemia by studying the records of 24 patients reported in the SFGM-TC database and one transplanted in the bone marrow unit in Hamburg. RESULTS: Median age at the time of transplant was 48 years (range, 24-64). The patients had previously received a median of 3 lines of therapy (range, 1-6) and 44% of them had refractory disease at time of transplant. Allogeneic stem cell transplantation after myeloablative (n=12) or reduced-intensity (n=13) conditioning yielded an overall response rate of 92% and immunofixation-negative complete remission in 50% of evaluable patients. With a median follow-up of 64 months among survivors (range, 11-149 months), 5-year overall survival and progression-free survival rates were respectively, 67% (95% CI: 46-81) and 58% (95% CI: 38-75). The 5-year estimated risk of progression was 25% (95% CI: 10-36%), with only one relapse among the 12 patients who entered complete remission, versus 5 in the 12 patients who did not. Only one of the 6 relapses occurred more than three years post-transplant. CONCLUSIONS: Allogeneic stem cell transplantation yields a high rate of complete remissions and is potentially curative in poor-risk Waldenström's macroglobulinemia.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Sociedades Médicas , Macroglobulinemia de Waldenström/cirugía , Adulto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Macroglobulinemia de Waldenström/mortalidad , Macroglobulinemia de Waldenström/patología , Adulto JovenRESUMEN
BACKGROUND: Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs. METHODS: In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia. RESULTS: The median duration of neutropenia (neutrophil count, <500 cells/mm3) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; P < .05), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; P < .01). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%. CONCLUSIONS: Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.
Asunto(s)
Antifúngicos/administración & dosificación , Micosis/tratamiento farmacológico , Neutropenia/complicaciones , Infecciones Oportunistas/tratamiento farmacológico , Adulto , Anciano , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Distribución de Chi-Cuadrado , Ácido Desoxicólico/administración & dosificación , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Femenino , Fiebre/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Micosis/complicaciones , Micosis/diagnóstico , Micosis/prevención & control , Infecciones Oportunistas/prevención & control , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
The recommendations that we formulate in this document come from LABAC, SFBC and FAEEQ. They describe the different steps from the initial application of quality controls, based on risk analysis: the changes of reagent batches or internal quality controls (IQC) batches, the course when IQC are not in accordance with references, the choice of external quality evaluation and the interpretation of its results, the comparability of results obtained in several analysers used in the same laboratory. Lastly, measurement uncertainty, robustness of methods and specificities of near-patient biology and rapid tests are described. Note that these recommendations cannot develop all cases that we could find in laboratories. It remains necessary to carry out an objective strategy, supported with documentary evidences.
Asunto(s)
Acreditación/normas , Biología/normas , Técnicas de Laboratorio Clínico/normas , Control de Calidad , Estudios de Seguimiento , Francia , Unidades Hospitalarias/normas , Humanos , Laboratorios/normasRESUMEN
BACKGROUND AND OBJECTIVES: High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM). In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen. The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT. DESIGN AND METHODS: This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry. RESULTS: Patients received a median of three lines of therapy prior to RIC allogeneic SCT. The most widely used conditioning regimens were fludarabine + busulfan + antithymocyte globulin (n=43) and fludarabine + total body irradiation (n=21). Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19). The median follow-up was 37 months (range, 16 to 77 months). In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively. The 3-year cumulative incidences of TRM were 32%, 28% and 63%, respectively. The incidence of relapse was 9.6%. INTERPRETATION AND CONCLUSIONS: Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Linfoma no Hodgkin/cirugía , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/administración & dosificación , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Recolección de Datos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Francia , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estimación de Kaplan-Meier , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Inducción de Remisión , Estudios Retrospectivos , Terapia Recuperativa , Análisis de Supervivencia , Tasa de Supervivencia , Linfocitos T , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal TotalRESUMEN
BACKGROUND: There is, until now, no prognostic grading system for infections occurring in allogeneic stem cell transplant (SCT) recipients. The aim of this study was to determine the prognostic value of a grading system of infectious complications in predicting death. METHODS: For the purposes of a prospective allogeneic SCT trial, we classified severity of infections in 3 grades according to expected rates of mortality (>or= 60% for grade 3). We prospectively recorded the type and time of occurrence of 440 infectious events in 190 consecutive patients until 6 months after transplant. We used multivariate Cox models with time-dependent covariates to analyze the relationship between the grade of severity of each infectious episode and mortality due or not due to infection, adjusting for possible confounders. RESULTS: Only patients with grade 3 infections had a significantly increased risk of death (P<.0001). The risk was not modified when the occurrence of acute graft-versus-host disease or the dose of IVIg administered were considered. Occurrence of a grade 1 and 2 infection had no additional influence. CONCLUSION: Our grading system identifies the most medically important, life-threatening infections and allow high-risk patients to be identified. We suggest grade 3 infections should be given priority in the evaluation of anti-infectious strategies.
Asunto(s)
Infecciones/clasificación , Infecciones/mortalidad , Índice de Severidad de la Enfermedad , Trasplante de Células Madre/mortalidad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Trasplante HomólogoRESUMEN
Infection is a leading cause of mortality in hematology. Although data on nosocomial infections are available, little is known about events falling into the broader category of healthcare-associated infections. Our aim was to evaluate the incidence and causes of healthcare-associated infections in hematology patients, comparatively with nosocomial infections. Using predefined criteria, we classified 223 infectious episodes in 137 patients for their association with healthcare and nosocomial occurrence. Of the 223 infectious episodes, 204 (91%) were healthcare associated, 94/223 (42%) were also nosocomial, and 9% were community-acquired. Healthcare-associated infections should be preferred to nosocomial infections--which underestimates half of the healthcare-associated infections--as quality indicators for preventive programs.
Asunto(s)
Infección Hospitalaria/epidemiología , Hematología/métodos , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/epidemiología , Bacteriemia/prevención & control , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/prevención & control , Infección Hospitalaria/prevención & control , Atención a la Salud/métodos , Femenino , Hematología/tendencias , Humanos , Incidencia , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Leucemia/microbiología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Trasplante de Células MadreRESUMEN
In all, 625 patients with acute lymphoblastic leukemia (ALL) entered the Leucémie Aiguë Lymphoblastique de l'Adulte-94 trial from June 1994 to June 1999, and received a 4-week induction therapy followed either by chemotherapy alone or stem cell transplantation (SCT). In a clinical phase II study, 40 patients with standard- or high-risk ALL - except Philadelphia chromosome-positive ALL -, relapsing at least 3 months after the beginning of therapy and who did not receive any SCT, received a rescue protocol combining amsacrine 120 mg/m(2)/day, days 1-3, cytarabine 1 g/m(2)/12 h, days 1-5, and etoposide 100 mg/m(2)/day, days 1-5. All relapses occurred 'on therapy'. In all, 16 patients (40%) achieved a second complete remission. The median time to neutrophil recovery >0.5 x 10(9)/l was 27 days. The median time to platelet recovery >50 x 10(9)/l was 28 days. Extra-hematologic toxicity was mild (only one toxic death from severe infection). The median overall survival was 5.4 months. The median disease-free survival (DFS) was 3.2 months with a 3-year DFS of 12%. Unfavorable prognostic factors for complete remission achievement were: high-risk ALL at diagnosis (P=0.03), and white blood cell count at relapse >or=30 x 10(9)/l (P=0.02). No relationship was found between survival and any characteristics of the disease. Four patients underwent allogeneic SCT (two phenoidentical and two genoidentical) and three patients received autologous SCT. This treatment combining amsacrine, cytarabine, and etoposide was therefore effective and well tolerated in 'on-therapy'-relapsed ALL. However, the median DFS was short requiring the rapid completion of effective intensive postremission therapy.