RESUMEN
An abnormal increase of nonleukemic blastic-appearing lymphocytes in bone marrow (BM) specimens has been reported after unrelated cord blood transplantation (UCBT). This study analyzed the incidence, chronology, biological features, and clinical significance of elevated numbers of these cells in a series of 165 consecutive adult patients demonstrating myeloid engraftment after myeloablative UCBT in a single institution. The patients' BM samples were routinely evaluated by cytomorphology at different time points after UCBT. When ≥5% of blastic-appearing cells were detected by cytomorphology in the BM, samples were also evaluated by multiparametric flow cytometry to characterize these cells. Systematic chimerism analyses of BM samples using PCR amplification of short tandem repeat markers were performed. Forty-three patients (cumulative incidence, 26.1%) demonstrated ≥5% of nonmalignant blastic-appearing cells in BM after a median of 101 days after UCBT (range, 28-377 days). All of these patients had full-donor chimerism and a clinical course without leukemic relapse. Multiparametric flow cytometry analyses performed in 36 of the 43 patients showed a polyclonal expansion of B lymphocytes with a broad spectrum of maturation stages. An increased number of nonmalignant blastic-appearing cells was significantly associated with a high number of lymphocytes infused at the time of UCBT and with low rates of acute and chronic extensive graft-versus-host disease, suggesting a potential immunoregulatory role of these cells. The observation of ≥5% nonmalignant blastic-appearing cells in BM samples after myeloablative UCBT is frequent, and these should be distinguished from malignant blasts.
Asunto(s)
Células de la Médula Ósea/inmunología , Células de la Médula Ósea/patología , Médula Ósea/patología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Sangre Fetal/citología , Adulto , Médula Ósea/inmunología , Células de la Médula Ósea/citología , Femenino , Sangre Fetal/inmunología , Humanos , Recuento de Linfocitos , Masculino , Pronóstico , Quimera por TrasplanteRESUMEN
Clinical studies focused on disease-specific outcomes of cord blood transplant (CBT) from unrelated donors are limited. We analyzed the outcome and prognostic factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a single institution. Conditioning regimens were based on the combination of thiotepa, busulfan (Bu), cyclophospamide (Cy), or fludarabine (Flu), and antithymocyte globulin (ATG). Cumulative incidence of myeloid and platelet engraftment was 96% and 73% at a median time of 20 and 62 days, respectively. Engraftment was significantly faster for patients receiving higher doses of CD34(+) cells. Confidence Interval of graft-versus-host disease (GVHD), acute GVHD (aGVHD) grade II-IV, III-IV, and extensive chronic GVHD (cGVHD) were 26%, 15%, and 30%, respectively. Leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse at 2 years were 42%, 39%, and 19%, respectively. Low number of total nucleated cells (TNC) had a negative impact on NRM and LFS. Patients transplanted in first complete remission (CR1) receiving TNC above 2 x 10(7)/kg had a 4-year LFS of 75%. These results show that CBT from unrelated donors is a curative treatment for a substantial number of patients with high-risk AML, particularly if transplant is performed with highly cellular units in patients in first CR.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Antígenos CD34/análisis , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Estadística como Asunto , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Clinical studies focused on outcomes of umbilical cord blood transplantation (UCBT) for patients with chronic myelogenous leukemia (CML) in need of allogeneic stem cell transplantation and lacking an HLA-matched adult donor are limited. We analyzed the outcome of 26 adults with CML receiving single-unit UCBT from unrelated donors after myeloablative conditioning at a single institution. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 7 patients (27%) were in first chronic phase (CP), 11 (42%) were in second CP, 2 (8%) were in accelerated phase (AP), and 6 (23%) were in blast crisis (BC). The cumulative incidence (CI) of myeloid engraftment was 88% at a median time of 22 days and was significantly better for patients receiving higher doses of CD34(+) cells. The CI of acute graft-versus-host disease (GVHD) grade II-IV was 61%, that of acute GVHD grade III-IV was 39%, and that of chronic extensive GVHD was 60%. Treatment-related mortality (TRM) was 41% for patients undergoing UCBT while in first or second CP and 100% for patients in AP or BC (P < .01). After a median follow-up of 8 years, none of the patients relapsed, giving an overall disease-free survival (DFS) at 8 years of 41%. The DFS for patients undergoing UCBT while in any CP was 59%. These results demonstrate that UCBT from unrelated donors can be a curative treatment for a substantial number of patients with CML. Advances in supportive care and better selection of cord blood units and patients are needed to improve TRM.
Asunto(s)
Donantes de Sangre , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Adulto , Causas de Muerte , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Supervivencia sin Enfermedad , Femenino , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/epidemiología , Histocompatibilidad , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Recuento de Plaquetas , Recurrencia , Estudios Retrospectivos , Quimera por Trasplante , Resultado del Tratamiento , Adulto JovenRESUMEN
There is no information on the efficacy and safety of anticytomegalovirus (CMV) prophylaxis with intravenous ganciclovir or oral valganciclovir after unrelated cord-blood transplantation (UCBT). This issue was addressed in 151 adults (117 CMV-seropositive) undergoing UCBT at a single institution. The first 38 CMV-seropositive recipients were assigned to receive prophylactic ganciclovir, and the next 79 were given valganciclovir after engraftment. The cumulative incidence (CI) of CMV infection and disease was similar in patients receiving valganciclovir or ganciclovir (59% versus 55%, P = .59; and 9% versus 18%, P = .33, respectively). The toxicity profile and CI of nonrelapse mortality (CMV) and infection-related mortality did not differ between drugs. Patients receiving valganciclovir required fewer visits to the day hospital (P = .04). The CI of CMV infection and disease in 34 CMV-seronegative recipients was 12% and 6%, indicating that tight CMV monitoring is mandatory in this subset. The recipient's CMV serostatus, acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were the main risk factors for CMV infection, and aGVHD for CMV disease. This study suggests that prophylaxis with oral valganciclovir is as safe and effective as intravenous ganciclovir for preventing CMV infection and disease after UCBT, but valganciclovir reduces the use of hospital resources.
Asunto(s)
Antivirales/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Citomegalovirus/epidemiología , Ganciclovir/análogos & derivados , Ganciclovir/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Administración Oral , Adolescente , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Estudios de Cohortes , Infecciones por Citomegalovirus/prevención & control , Esquema de Medicación , Femenino , Estudios de Seguimiento , Ganciclovir/administración & dosificación , Ganciclovir/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Recursos en Salud/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Incidencia , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Premedicación , Pronóstico , Factores de Riesgo , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Valganciclovir , Adulto JovenRESUMEN
BACKGROUND: Cord blood transplant is a feasible treatment alternative for adult patients with hematologic malignancies lacking a suitable HLA-matched donor. However, the kinetics of myeloid recovery is slow, and primary graft failure cannot be detected easily early after transplantation. We investigated the impact of hematopoietic chimerism status from unselected marrow cells 14 days after transplantation on predicting engraftment after a cord blood transplant. DESIGN AND METHODS: Seventy-one adult patients with hematologic malignancies undergoing single-unit unrelated donor cord blood transplantation after a myeloablative conditioning regimen were included in the study. All patients received conditioning regimens based on busulfan, thiotepa and antithymocyte globulin. Chimerism status was assessed analyzing short tandem repeat polymorphisms. RESULTS: The cumulative incidence of myeloid engraftment at 1 month was significantly lower in patients with mixed chimerism than in those with complete donor chimerism (55% vs. 94%; p<0.0001). For patients achieving myeloid recovery, the median time of engraftment was 16 days when donor chimerism at day + 14 was higher than 90%, compared with 24 days when donor chimerism was below this level (p<0.001). A donor chimerism level of 65% was found to be the best cut-off point for predicting primary graft failure, with a sensitivity of 97% and a specificity of 80%. The incidence of primary graft failure was 67% for patients with less than 65% donor chimerism at day +14 as compared to only 2% for those with more than 65% donor chimerism (p<0.001). Patients with mixed chimerism also had a lower cumulative incidence of platelet engraftment than those with complete chimerism (62% vs. 89%; p=0.01). CONCLUSIONS: Donor-recipient chimerism status at day +14 predicts engraftment after a single-unit cord blood transplant in adults.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Neoplasias Hematológicas/cirugía , Quimera por Trasplante , Adolescente , Adulto , Plaquetas/metabolismo , Células de la Médula Ósea/metabolismo , Femenino , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Cinética , Masculino , Persona de Mediana Edad , Células Mieloides/metabolismo , Tasa de Supervivencia , Factores de Tiempo , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Immune-mediated inflammatory diseases (IMID) are chronic and highly disabling diseases that share inflammatory sequences and immunological dysregulations. Considered as a disease in itself, the prevalence of IMID is virtually unknown. The aim of this study was to assess the prevalence of 10 selected UDI, including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, hidradenitis suppurativa, sarcoidosis and uveitis in Spain. METHODS: cross-sectional epidemiological study of point prevalence was made. This study was carried out through a series of computerized interviews in households chosen at random in 17 autonomous communities in Spain. A structured questionnaire was used to determine the frequency of diagnosis and the concurrence of 10 IMID in the respondents and other individuals belonging to the same family nucleus. The point prevalence estimates were used and compared with the objective of determining the frequency of IMID by age, sex and communities. The data were processed using Excel 2016 (Microsoft, Redmond, WA, USA) and the SPSS V.019 system (IBM Corp. Armonk, NY, USA) for statistical analysis using the usual statistical tests in this type of studies. RESULTS: Of the 7,980 respondents, 510 were diagnosed with an IMID, representing a cross-sectional study of 6.39% (95% CI: 6.02-6.76). One, two, three or more members of the family were affected in 87.2%, 7.8% and 5% of positive relatives in IMID, respectively. The most recurrent diseases were psoriasis (2.69% [95% CI: 2.32-3.06]) and rheumatic arthritis (1.07% [95% CI: 0.70-1.44]). There were differences in prevalence due to sex (p = 0.004) and age (p = 0.000). No significant differences were identified related to geographic location (p = 0.819). Attendance of at least 2 IMID was reported in 8.9% of respondents. CONCLUSIONS: The overall prevalence was of the IMID studied was 6.39%, psoriasis being the most frequent with 2.69%. This study constitutes an initial step to consider IMID as an independent disease within the health system..
OBJETIVO: Las enfermedades inflamatorias inmunomediadas (IMID) son enfermedades crónicas y altamente discapacitantes que comparten secuencias inflamatorias y desregulaciones inmunológicas. Considerada como una enfermedad en sí, la prevalencia de la IMID es prácticamente desconocida. El objetivo de este trabajo fue valorar la prevalencia de 10 IMID seleccionadas, incluyendo artritis reumatoide, psoriasis, artritis psoriásica, espondilitis anquilosante, colitis ulcerosa, enfermedad de Crohn, lupus eritematoso sistémico, hidrosadenitis supurativa, sarcoidosis y uveítis en España. METODOS: Se hizo un estudio epidemiológico transversal de prevalencia puntual. Este estudio llevó a cabo a través de una serie de entrevistas informatizadas en hogares elegidos al azar en 17 comunidades autónomas en España. Mediante un cuestionario estructurado se determinó la frecuencia de diagnóstico y las concurrencias de 10 IMID en los encuestados y otros individuos pertenecientes al mismo núcleo familiar. Las estimaciones de prevalencia pun- tual se utilizaron y compararon con el objetivo de determinar la frecuencia de IMID por edad, sexo y comunidades. Los datos fueron procesados utilizando el programa Excel 2016 (Microsoft, Redmond, WA, USA) y el sistema SPSS V.019 (IBM Corp. Armonk, NY, USA) para el análisis estadístico utilizando los test estadísticos habituales en este tipo de estudios. RESULTADOS: De los 7.980 encuestados, 510 fueron diagnosticados con una IMID, lo que representa un estudio transversal de un 6,39% (95% ci: 6,02-6,76). Uno, dos, tres o más miembros de la familia estaban afectados en un 87,2%, 7,8% y 5% de familiares positivos en IMID, respectivamente. Las enfermedades más recurrentes fueron psoriasis (2,69% [95% ci: 2,32-3,06]) y artritis reumática (1,07% [95% ci:0,70-1,44]). Se observaron diferencias en la prevalencia debidas al sexo (p=0,004) y edad (p=0,000). No se identificaron diferencias significativas relacionadas con la localización geográfica (p=0,819). Se reportó concurrencia de al menos 2 IMID en un 8,9% de encuestados. CONCLUSIONES: La prevalencia global fue de las IMID estudiadas fue del 6,39 % siendo las mas frecuentes la psoriasis con el 2,69%. Este estudio constituye un paso inicial para considerar la IMID como una enfermedad independiente dentro del sistema sanitario.
Asunto(s)
Artritis/epidemiología , Hidradenitis Supurativa/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Sarcoidosis/epidemiología , Uveítis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis/inmunología , Estudios Transversales , Femenino , Hidradenitis Supurativa/inmunología , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Sarcoidosis/inmunología , España/epidemiología , Uveítis/inmunología , Adulto JovenRESUMEN
BACKGROUND: The natural history and its modulation by treatments administered for immune thrombocytopenia (ITP) in the clinical practice remains unknown. In addition, little information is available on the characteristics and management of ITP in Spain. METHODS: We conducted an observational, multicenter, registry in 70 Hematology Services from Spain between 2009 and 2011, which included children from 2 months of age and adults with primary ITP or another ITP diagnosed within the last 6 months (platelet count [PC] < 100 × 109/l). Patients were followed-up at 6 and 12 months. RESULTS: 484 patients were included (median [Q1, Q3] age 52 [29,74] years, 87.6% adults), 56% women, 10.5% with secondary ITP. Median (Q1, Q3) PC at diagnosis was 12 × 109/l (4, 32); 72% of patients had bleeding symptoms (62% cutaneous bleeding, 29% oral cavity bleeding, 18% epistaxis). 81% of patients with primary ITP received first-line treatment, mainly with corticosteroids (>6 weeks in 59% of cases), either alone (41%) or associated with intravenous immunoglobulin (33%). The response (≥30 × 109/L) to first-line treatment was 92%. A total of 19% of patients received second-line treatment and 6% additional treatments. At 12 months, 74% of primary ITP patients maintained a PC ≥ 100 × 109/L in absence of treatment (10% still had hemorrhagic manifestations). CONCLUSIONS: Characteristics of Spanish ITP patients are comparable to those from other countries. Although a high response rate to first-line treatments is observed, at 1 year, the disease persists in around one quarter of patients. Overall therapeutic management in Spain conforms to current recommendations, except for an excessive duration of corticosteroids therapy.
Asunto(s)
Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Algoritmos , Biomarcadores , Niño , Preescolar , Comorbilidad , Manejo de la Enfermedad , Femenino , Hemorragia/etiología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Masculino , Persona de Mediana Edad , Fenotipo , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/epidemiología , Púrpura Trombocitopénica Idiopática/etiología , Sistema de Registros , España/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Invasive fungal disease (IFD) treatment is challenging in hematologic patients due to drug interactions and toxicities that limit the use of the antifungal agents. AIMS: To analyze retrospectively in terms of safety and potential efficacy anidulafungin therapy, alone or in combination. METHODS: Our institutional guidelines recommended anidulafungin treatment in hematologic patients with suspected IFD and concomitant renal or liver impairment (to avoid drug interactions and preserve organ function). RESULTS: From 2008 to 2013, 24 episodes of IFD occurring in 21 patients were classified as proven (4 cases), probable (15 cases) and possible (5 cases). Anidulafungin was administered alone (13%) or in combination (88%). Eight (33%) episodes were resolved, using monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve cases (50%) were registered as failure (death due to IFD progression in 4 patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%) were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn in any case due to toxicity. CONCLUSIONS: Anidulafungin therapy, alone or in combination, could be considered in hematologic patients with IFD and concomitant liver or renal impairment. Due to the low number of patients, we cannot draw any conclusion about efficacy.
Asunto(s)
Antifúngicos/uso terapéutico , Equinocandinas/uso terapéutico , Enfermedades Renales/complicaciones , Hepatopatías/complicaciones , Micosis/complicaciones , Micosis/tratamiento farmacológico , Adulto , Anciano , Anidulafungina , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Left ventricular hypertrophy (LVH) is an important predictor of cardiovascular risk, and its detection contributes to risk stratification. The aims of the present study were to estimate the prevalence of echocardiographic LVH and to evaluate the influence of echocardiography (ECHO) on cardiovascular risk stratification in hypertensive patients presenting in primary care. METHODS: In this cross-sectional study, 250 patients recently diagnosed with mild hypertension underwent clinical evaluation including electrocardiography (ECG), microalbuminuria measurement, 24-h blood pressure monitoring and ECHO. Level of cardiovascular risk was stratified, initially using routine procedures including ECG to assess target organ damage and then again after detection of LVH by ECHO. RESULTS: The frequency of echocardiographic LVH was 32%, substantially higher than that detected by ECG (9%). Initial cardiovascular risk stratification yielded the following results: 30% low risk, 49% medium risk, 16% high risk, and 5% very high risk subjects. The detection of LVH by ECHO provoked a significant change in the risk strata distribution, particularly in those patients initially classified as being at medium risk. In this group, 40% of subjects were reclassified as high risk subjects according to ECHO information. The new classification was as follows: 23% low risk, 30% medium risk, 42% high risk, and 5% very high risk subjects. CONCLUSIONS: A substantial proportion of mildly hypertensive patients presenting in primary care have LVH determined by ECHO. Our results suggest that this procedure could significantly improve cardiovascular risk stratification in those patients with multiple risk factors, but no evidence of target organ damage by routine investigations.
Asunto(s)
Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/epidemiología , Albuminuria , Monitoreo Ambulatorio de la Presión Arterial , Estudios Transversales , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Examen Físico , Prevalencia , Atención Primaria de Salud , Medición de RiesgoRESUMEN
Chronic immune thrombocytopenic purpura (ITP) is generally a more benign disease than previously thought. Currently it is recommended that only those patients with severe and/or symptomatic thrombocytopenia definitely require treatment. Additional factors, such as age, lifestyle, and uremia can also influence the hemorrhagic risk and should be carefully assessed before decision-making on the appropriate management of patients with less severe forms of ITP. The recent introduction of new classes of therapeutic agents such as rituximab and the thrombopoietic growth factors has had a major impact on the management of ITP. Updated treatment guidelines have recently been made available but they are based largely on expert opinion rather than on high-quality clinical trial evidence. This structured review is focused on the management of adults with chronic ITP, including the use of new classes of agents.
RESUMEN
BACKGROUND: Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia. METHODS: In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy. RESULTS: Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam). CONCLUSION: The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia. KEYWORDS: cefepime, piperacillin-tazobactam, amikacin, empirical antibiotic therapy, febrile neutropenia, haematological malignancy