RESUMEN
BACKGROUND: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. METHODS: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. RESULTS: Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). CONCLUSIONS: High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.
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Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Mucormicosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Preescolar , Desbridamiento , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mucormicosis/cirugía , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To report an outbreak due to an unusual strain of Enterococcus faecium containing both the vanA and vanB genes, in France, where the rate of glycopeptide-resistant enterococci (GRE) is below 1%. METHODS: Cases were patients infected or colonized with GRE on the haematology ward. Contact patients were screened by real-time PCR performed on rectal swabs. Clinical features were compared for GRE-positive and GRE-negative patients. GRE isolates were characterized by phenotypic and molecular methods including PFGE. Conjugation experiments were performed to identify van genetic support. RESULTS: After the index patient presented a bacteraemia with vanA/vanB E. faecium, 56 contact patients were screened, 7 of whom were found to be GRE positive: 6 additional cases with vanA/vanB E. faecium and 1 with GRE carrying vanA only. PFGE confirmed the clonal relationship of the seven vanA/vanB E. faecium strains, whereas the vanA isolate was distinct. Only the vanA gene could be transferred to enterococcal recipients by conjugation, and it was probably localized on a mobile genetic element. All isolates were resistant to vancomycin (MICâ>â256 mg/L) and teicoplanin (MICâ=â24-32 mg/L), but were susceptible to tigecycline (MICâ=â0.09 mg/L), linezolid (MICâ=â0.75 mg/L) and daptomycin (MICâ=â1-2 mg/L). Significant differences (Pâ<â0.001) between carriers and non-carriers of GRE were observed for the median duration of hospitalization (57 days versus 16.5 days) and of neutropenia (40 days versus 6 days), the median number of antibiotics used (5 versus 1.5) and the duration of glycopeptide treatment (14.5 days versus 0 days). CONCLUSIONS: vanA/vanB E. faecium strains, although rare, can emerge in the absence of previous outbreaks of vanA-GRE or vanB-GRE.
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Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Enterococcus faecium/genética , Glicopéptidos/farmacología , Enfermedades Hematológicas/genética , Resistencia a la Vancomicina/genética , Brotes de Enfermedades , Enterococcus faecium/metabolismo , Francia/epidemiología , Glicopéptidos/uso terapéutico , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/epidemiología , Unidades Hospitalarias , Humanos , Resistencia a la Vancomicina/efectos de los fármacosRESUMEN
PURPOSE: Human herpesvirus 6 (HHV6) is an emerging cause of interstitial pneumonia in immunocompromised hosts. However, the clinical significance of a positive PCR test for HHV6 in respiratory samples from patients with hematological malignancies remains unclear. METHODS: We retrospectively studied the features and outcomes of 29 critically ill hematology patients with acute respiratory failure and lung pulmonary infiltrates visible on a chest radiograph, who tested positive for a qualitative PCR for HHV6 in bronchoalveolar lavage fluid. RESULTS: Of the 29 patients, 18 (62%) were stem cell transplant recipients and 11 (38%) had received chemotherapy. All patients had a fever. Clinical manifestations consistent with extra-pulmonary HHV6 disease were noted in 17 (59%) patients. One or more co-pathogens were found in 25 (86%) patients. The four remaining patients diagnosed with HHV6 pneumonia and subsequently recovered with foscarnet therapy. Antiviral therapy was also given to seven patients with co-infections, of whom two ultimately died. CONCLUSIONS: In most cases, HHV6 recovered from BAL fluid is a co-pathogen whose clinical relevance remains undetermined. However, in some cases, HHV6 is the only pathogen, along with disseminated systemic viral disease, and the patient is likely to benefit from foscarnet therapy.
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Líquido del Lavado Bronquioalveolar/virología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 6/patogenicidad , Síndrome de Dificultad Respiratoria/virología , Adulto , Trasplante de Médula Ósea/patología , Broncoscopía/métodos , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/virología , Hematología , Herpesvirus Humano 6/crecimiento & desarrollo , Humanos , Huésped Inmunocomprometido , Unidades de Cuidados Intensivos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Neumonía/virología , Reacción en Cadena de la Polimerasa , Síndrome de Dificultad Respiratoria/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Double unrelated cord blood transplant (dUCBT) has been used to circumvent cell dose limitation of single UCBT; however, few data are available describing outcomes, infectious disease, and immune recovery. We analyzed 35 consecutive dUCBT recipients with high-risk malignant disorders (n=21) and bone marrow failure syndromes (n=14). Median follow-up was 32 months. Conditioning regimen was myeloablative in 14 and reduced intensity in 21 patients. Median infused nucleated cell dose was 4 × 10(7) /kg. Median time to absolute neutrophil count >0.5 × 10(9) /L was 25 days. Cumulative incidence (CI) of acute grade II-IV graft-versus-host disease was 47%. Estimated overall survival at 2 years was 48%. CI of first viral infections at 1 year was 92%. We observed 49 viral infections in 30 patients, 34 bacterial infections in 19 patients, and 16 fungal or parasitic infections in 12 patients. Lymphocyte subset analyses were performed at 3, 6, 9, and >12 months after dUCBT. Decreased T-cell and B-cell counts with expansion of natural killer cells were observed until 9 months post transplantation. Recovery of thymopoiesis measured by T-cell receptor excision circles was impaired until 9 months after dUCBT, when the appearance of new thymic precursors was observed. Delayed immune recovery and high incidence of infectious complications were observed after dUCBT in patients with high-risk hematological diseases.
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Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Síndrome Inflamatorio de Reconstitución Inmune/patología , Adolescente , Adulto , Anemia Aplásica , Infecciones Bacterianas/etiología , Enfermedades de la Médula Ósea , Trastornos de Fallo de la Médula Ósea , Niño , Femenino , Hemoglobinuria Paroxística/terapia , Humanos , Masculino , Persona de Mediana Edad , Micosis/etiología , Neoplasias/terapia , Enfermedades Parasitarias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Virosis/etiología , Adulto JovenRESUMEN
Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow-up of 23 months, the estimated 2 years overall survival was 80 +/- 17% and 33 +/- 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA-matched UCB thus enables salvage treatment of high-risk patients with BMFS.
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Enfermedades de la Médula Ósea/terapia , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Adolescente , Adulto , Anemia Aplásica/terapia , Niño , Métodos Epidemiológicos , Anemia de Fanconi/terapia , Femenino , Supervivencia de Injerto , Humanos , Masculino , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergillus/aislamiento & purificación , Manejo de la Enfermedad , Anticuerpos Antifúngicos/sangre , Antifúngicos/farmacología , Aspergilosis/complicaciones , Aspergilosis/inmunología , Aspergillus/efectos de los fármacos , Aspergillus/inmunología , Biopsia/métodos , Lavado Broncoalveolar , Diagnóstico Precoz , Flucitosina/farmacología , Flucitosina/uso terapéutico , Galactosa/análogos & derivados , Humanos , Huésped Inmunocomprometido , Pruebas Inmunológicas , Aspergilosis Pulmonar Invasiva/diagnóstico , Itraconazol/farmacología , Itraconazol/uso terapéutico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Imagen por Resonancia Magnética , Mananos/análisis , Pruebas de Sensibilidad Microbiana , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/terapia , Nitrilos/farmacología , Nitrilos/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Tomografía Computarizada por Rayos X , Triazoles/farmacología , Triazoles/uso terapéutico , Voriconazol/farmacología , Voriconazol/uso terapéuticoRESUMEN
Bronchiolitis obliterans (BO) is a potentially life-threatening complication following allogeneic stem cell transplantation (SCT) and usually carries a poor prognosis. Immunosuppressive medications are the main treatment, but are rarely effective, especially when the disease is severe. Thus, both early detection and alternative therapeutic approaches of post SCT BO are needed. We report our experience with Budesonide/Formoterol, an inhaled steroid and long-acting bronchodilatator combination, in a group of patients with mild to moderately severe BO after SCT whose systemic immunosuppressive treatment had not been modified. Thirteen patients were treated. The diagnosis of BO was based on the presence of respiratory symptoms and air-trapping on expiratory lung high-resolution computed tomography in all patients, associated with irreversible airflow obstruction in seven cases. The median follow-up was 12.8 months (range: 5-29 months). All patients improved clinically, and both forced expiratory volume in 1 (FEV(1)) and mean expiratory flow values increased significantly during follow-up (534+/-268 ml in absolute values and 36+/-27% compared to pretreatment values for FEV(1); P<0.02). These encouraging results provide new insights in the therapeutic approach of BO after SCT and require confirmation in a larger group of patients with a longer follow-up.
Asunto(s)
Bronquiolitis Obliterante/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Budesonida/administración & dosificación , Etanolaminas/administración & dosificación , Glucocorticoides/administración & dosificación , Trasplante de Células Madre , Administración por Inhalación , Adolescente , Adulto , Bronquiolitis Obliterante/diagnóstico por imagen , Bronquiolitis Obliterante/etiología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Fumarato de Formoterol , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía , Trasplante HomólogoRESUMEN
We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.
Asunto(s)
Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas , Adolescente , Enfermedades Óseas/etiología , Enfermedades Óseas/mortalidad , Enfermedades Óseas/psicología , Catarata/etiología , Catarata/mortalidad , Catarata/psicología , Niño , Preescolar , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Trastornos de Alimentación y de la Ingestión de Alimentos/mortalidad , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/psicología , Humanos , Hipotiroidismo/etiología , Hipotiroidismo/mortalidad , Hipotiroidismo/psicología , Incidencia , Lactante , Infecciones , Artropatías/etiología , Artropatías/mortalidad , Artropatías/psicología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/psicología , Masculino , Neoplasias Primarias Secundarias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo , Irradiación Corporal TotalRESUMEN
The increase use of immunosuppressive treatments in patients with solid cancer and/or inflammatory diseases requires revisiting our practices for the prevention of infectious risk in the care setting. A review of the literature by a multidisciplinary working group at the beginning of 2014 wished to answer the following 4 questions to improve healthcare immunocompromised patients: (I) How can we define immunocompromised patients with high, intermediate and low infectious risk, (II) which air treatment should be recommended for this specific population? (III) What additional precautions should be recommended for immunocompromised patients at risk for infection? (IV) Which global environmental control should be recommended? Based on data from the literature and using the GRADE method, we propose 15 recommendations that could help to reduce the risk of infection in these exposed populations.
Asunto(s)
Huésped Inmunocomprometido , Control de Infecciones , Infecciones , Microbiología del Aire , Susceptibilidad a Enfermedades , Francia , Humanos , Guías de Práctica Clínica como Asunto , Factores de RiesgoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Bronquiolitis Obliterante/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Factores Inmunológicos/uso terapéutico , Adolescente , Adulto , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/cirugía , Broncodilatadores/uso terapéutico , Resultado Fatal , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Inmunosupresores , Macrólidos/uso terapéutico , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Rituximab , Tacrolimus/uso terapéutico , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Recurrencia , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
5'-Deoxy-5-fluorouridine (5'-dFUrd) is a new antineoplastic agent which possesses a higher therapeutic index in several experimental tumors compared to other fluoropyrimidines. During a Phase I trial, 5'-dFUrd, 1 to 15 g/sq m/week, was administered to patients as a 25- to 35-min i.v. infusion. Plasma kinetics and metabolism of 5'-dFUrd were investigated. The unmetabolized drug was measured by a high-performance liquid chromatography assay. 5-Fluorouracil and 5,6-dihydrofluorouracil, the two detected plasma metabolites, were quantitated by a gas chromatography-mass spectrometry methodology with a detection limit of 0.07 microM for both metabolites. The disposition of 5'-dFUrd in humans at therapeutic doses followed a nonlinear kinetic process. Plasma concentrations of 5-fluorouracil generated in vivo represented approximately 6% of 5'-dFUrd concentrations and the 5-fluorouracil half-life ranged from 8.8 to 27.1 min. High plasma values of 5,6-dihydrofluorouracil (14.5 to 30 microM) were observed in patients, indicating the importance of this pathway in humans.
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Floxuridina/metabolismo , Neoplasias del Colon/metabolismo , Evaluación de Medicamentos , Floxuridina/toxicidad , Humanos , Isomerismo , Cinética , Metástasis de la Neoplasia , Neoplasias Pancreáticas/metabolismoRESUMEN
The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.
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Antibióticos Antineoplásicos/farmacología , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Leucemia/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Células Madre/efectos de los fármacos , Aclarubicina , Relación Dosis-Respuesta a Droga , Doxorrubicina/metabolismo , Doxorrubicina/uso terapéutico , Humanos , Técnicas In Vitro , Naftacenos/farmacología , Naftacenos/uso terapéutico , Ensayo de Tumor de Célula MadreRESUMEN
PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.
Asunto(s)
Trasplante de Médula Ósea , Leucemia Megacarioblástica Aguda/terapia , Síndromes Mielodisplásicos/terapia , Neoplasias Primarias Secundarias/terapia , Trasplante Homólogo , Adolescente , Adulto , Femenino , Francia , Humanos , Leucemia Megacarioblástica Aguda/etiología , Leucemia Megacarioblástica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/mortalidad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/mortalidad , Evaluación de Resultado en la Atención de Salud , Análisis de SupervivenciaRESUMEN
Poor graft function (PGF) is a frequent cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To study the value of granulocyte colony-stimulating factor (G-CSF) in PGF, we retrospectively analyzed 81 episodes of PGF in 66 patients transplanted from 01/94 to 01/99 from an HLA-identical sibling (n = 45) or an unrelated (n = 21) donor. Median age was 29 years, 55 patients had malignancies. A total of 11 patients received a CD34+ selected graft. Viral infections (25%), myelotoxic drug (33%), fungal/bacterial infections (14%), and GVHD (31%) were present before PGF diagnosis. Median time from allo-HSCT to PGF was 75 (25-474) days. All patients were treated with G-CSF. In 77/81 episodes, there was a response that was sustained in 57. A total of 27 patients presented an increase of white cell count (WBC) >0.1 x 10(9)/l after 3 days of G-CSF. The 5-year survival was 37% and was significantly better in patients with increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (65 vs 18%, P < 0.0001). In multivariate analysis, increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (P = 0.002) was associated with better survival, while BuCy-based conditioning (P = 0.02) and GVHD (P = 0.005) were associated with higher risk of death. In conclusion, hematological response after 3 days with G-CSF predicted a better survival for patients with PGF after allo-SCT.
Asunto(s)
Supervivencia de Injerto/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Neoplasias/mortalidad , Adolescente , Adulto , Infecciones Bacterianas/etiología , Infecciones Bacterianas/mortalidad , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Micosis/etiología , Micosis/patología , Neoplasias/complicaciones , Neoplasias/terapia , Recuperación de la Función/efectos de los fármacos , Trasplante Homólogo , Resultado del Tratamiento , Virosis/etiología , Virosis/mortalidadRESUMEN
We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Hepatitis C Crónica/epidemiología , Donadores Vivos , Adolescente , Adulto , Anemia/terapia , Niño , Femenino , Hepatitis C Crónica/transmisión , Prueba de Histocompatibilidad , Humanos , Incidencia , Leucemia/terapia , Pruebas de Función Hepática , Masculino , Trasplante HomólogoRESUMEN
Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neumonía por Pneumocystis/prevención & control , Recuento de Linfocito CD4 , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Inmunosupresores/efectos adversos , Incidencia , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/prevención & control , Neumonía por Pneumocystis/inducido químicamente , Neumonía por Pneumocystis/tratamiento farmacológico , Premedicación , Estudios Retrospectivos , Trasplante Homólogo , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Over the last 25 years, the numbers of hematopoietic stem cell transplant (SCT) patients have increased rapidly. Infections have been major obstacles for successful transplantation. Thus, infection prevention is very important in transplant recipients. As the results of transplantation have improved, the number of long-term survivors has increased. Vaccination is a potentially important strategy for reducing the risk for vaccine-preventable infections after SCT. The EBMT produced recommendations for vaccination of SCT recipients published in Bone Marrow Transplantation in 1995. This paper updates the previous recommendations based on current knowledge.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones Oportunistas/prevención & control , Vacunación/normas , Ensayos Clínicos como Asunto , Control de Enfermedades Transmisibles/métodos , Enfermedades Transmisibles , Europa (Continente) , Directrices para la Planificación en Salud , Humanos , Esquemas de Inmunización , Control de Infecciones/métodos , RiesgoRESUMEN
Marrow transplantation from unrelated donors has been linked with an increased risk of graft-versus-host disease (GVHD). In an attempt to lower the risk of acute GVHD we used CD34 marrow cell selection for T cell depletion. Since T cell depletion has been linked to an increased risk of relapse and an increased risk of marrow failure, we used PCR amplification of minisatellite sequences to investigate donor cell engraftment and RT-PCR amplification of recurrent chromosomal translocations to investigate the residual disease post-transplant. Twenty-three patients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those of 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34+ selected cell grafts, seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autologous bone marrow recovery. Analysis of the chimaerism status post-transplant in 36 patients who received unmanipulated marrow grafts showed that 31 patients (86%) had evidence of full donor engraftment. The difference in the incidence of mixed chimaerism profile between patients who received unmanipulated marrow graft and those receiving CD34+ selected cell grafts was statistically significant (P< 0.01). Nine patients who received CD34+ selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient transplanted for a Ph-positive acute leukaemia, and in two out of the eight patients with CML, the search fora fusion transcript was consistently negative after transplantation. Among the six patients with evidence of residual disease, three patients also had a mixed chimaerism profile and were given donor lymphocyte infusions. Minimal residual disease study was performed post-transplant in 16 patients who received unmanipulated marrow grafts. In 10 of 14 patients with CML, and in two patients with acute leukaemia the search for a fusion transcript was consistently negative after transplantation. The difference in the incidence of minimal residual disease between patients who received an unmanipulated marrow graft and those receiving CD34+ selected cell grafts was not statistically significantly significant, but numbers of patients included in this analysis are still few. In conclusion, our study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.
Asunto(s)
Purgación de la Médula Ósea/métodos , Trasplante de Médula Ósea , Leucemia/terapia , Síndromes Mielodisplásicos/terapia , Proteínas de Fusión Oncogénica , Quimera por Trasplante , Adolescente , Adulto , Antígenos CD34 , Niño , Preescolar , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Femenino , Proteínas de Fusión bcr-abl/análisis , Humanos , Leucemia/metabolismo , Masculino , Persona de Mediana Edad , Neoplasia Residual , Reacción en Cadena de la Polimerasa , Proteína 1 Compañera de Translocación de RUNX1 , Proteínas Recombinantes de Fusión/análisis , Factores de Transcripción/análisis , Trasplante HomólogoRESUMEN
An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a compact, three-dimensional spheroid complex from central adipocytes, fibroblastoid cells, and resident macrophages that compartmentalize myeloid, erythroid, and megakaryocyte progenitor cells and their progenies. The Hematon fraction is more than twofold more abundant in progenitor cells when compared to the mononuclear cell (MNC) fraction as gauged by cytological techniques and by analysis of granulocyte-macrophage colony-forming unit (GM-CFU) populations. Individual Hematons may produce, within 2-3 weeks, up to 50,000 hemopoietic cells of different cell lineages in organotypic microcultures. Recombinant human hematopoietic growth factors interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) significantly stimulated the endogenous cell production of some but not all of the individually treated Hematons, indicating the heterogeneity of factor-responsive cells within the Hematon population. Comparative observations of 184 BM aspirates support the hypothesis that the presence of Hematons in a BM aspirate correlates positively with homeostatic blood cell production, because the Hematon was present in normal BM (31/40) and it was rare among patients with myelodysplastic syndromes (15/53), acute myeloblastic leukemia (7/39), and chronic myelocytic leukemia (5/52). We suggest that the Hematon represents a unifying model around which the variability of fundamental BM functions and dysfunctions can be explored.