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1.
J Neurol Neurosurg Psychiatry ; 85(3): 279-83, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23704316

RESUMEN

OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive agent, sometimes used as a disease-modifying therapy for multiple sclerosis (MS). Several studies have reported the relative safety of this treatment but, to date, its efficacy has rarely been described. We performed a retrospective study to assess the safety and efficacy of MMF in patients with MS. METHODOLOGY: Three French MS centres included all of their patients treated by MMF. The main outcome criterion was annualised relapse rate (ARR) in the 1 year period after onset of MMF compared with the 1 year control period. Treatment with another immunosuppressive drug, such as mitoxantrone or cyclophosphamide, in the 2 years preceding initiation of MMF was included in a subgroup analysis. MMF safety and progression of the Expanded Disability Status Scale (EDSS) score were also assessed. RESULTS: 344 patients were included; 149 patients were previously treated with another immunosuppressant (IS group). Mean MMF treatment duration was 25.3±1.1 months. During the 1 year control period, ARR was 1.11±0.08, and for the 1 year treatment period, ARR was reduced significantly to 0.35±0.05 (p<0.0001, Wilcoxon paired test). Adverse events (occurring in 11% of patients) were mainly digestive disorders, benign infections, asthenia and transitory lymphopenia. Concerning the progression of disability, in the subgroup of patients without previous immunosuppressant treatment, EDSS remained stable between initiation and 1 year after the beginning of MMF. INTERPRETATION: Our results suggest that MMF can improve or stabilise MS patients and can be used as an alternative therapy.


Asunto(s)
Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Ácido Micofenólico/análogos & derivados , Adulto , Ciclofosfamida/uso terapéutico , Humanos , Inmunosupresores/efectos adversos , Mitoxantrona/uso terapéutico , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Estudios Retrospectivos , Prevención Secundaria , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
2.
Int J Clin Pharmacol Ther ; 49(8): 510-8, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21781651

RESUMEN

BACKGROUND: Filgrastim (Neu-pogen®, Amgen) and lenograstim (Granocyte®, Chugai Pharma) are chemically different granulocyte colony-stimulating factors (G-CSFs). Based on receptor-binding studies and in vitro potency assessment, a clinical superiority of lenograstim versus filgrastim has been postulated together with potential cost savings favouring lenograstim over filgrastim. OBJECTIVES: To compare the clinical efficacy of filgrastim and lenograstim based on current Summaries of Product Characteristics (SPCs) for both products taking into account published clinical trials in patients and healthy volunteers. SEARCH STRATEGY AND SELECTION CRITERIA: PubMed and citation lists of published articles were used to identify clinical trials with direct comparisons of filgrastim and lenograstim. All available clinical information directly comparing filgrastim and lenograstim has been accepted for evaluation. DATA COLLECTION: A total of 16 studies compared filgrastim with lenograstim. Four studies had a randomized, parallel-group design, 4 had a cross-over design and 8 studies were uncontrolled. RESULTS: Available data do not suggest a clinically remarkable difference between filgrastim and lenograstim in chemotherapy-induced neutropenia and the mobilisation of peripheral blood progenitor cells (PBPC) in patients and healthy donors. CONCLUSIONS: Both G-CSFs are recommended for clinical use according to instructions in the respective SPCs; there is no reason to prefer lenograstim over filgrastim in any of the approved indications for both. Costs calculations need to consider the advent of biosimilar filgrastim in Europe.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antineoplásicos/efectos adversos , Ensayos Clínicos como Asunto , Costos de los Medicamentos , Europa (Continente) , Filgrastim , Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Lenograstim , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico
3.
Am J Transplant ; 9(5): 1081-6, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19344432

RESUMEN

No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 +/- 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05-0.3 g/day) and 0.19 g/day (range 0.05-1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/cirugía , Trasplante de Riñón , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/terapia , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/inmunología , Masculino , Proyectos Piloto , Proteinuria , Grupos Raciales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Donantes de Tejidos/estadística & datos numéricos , Adulto Joven
4.
Respiration ; 76(3): 295-302, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18160817

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) is a severe hemodynamic disorder in which the pulmonary artery pressure is persistently elevated, leading to right-sided heart failure. Some studies have suggested an association between PH and myeloproliferative diseases (MPD). OBJECTIVES: This study describes clinical, hematological and hemodynamic characteristics of PH associated with MPD. METHODS: We retrospectively reviewed 10 cases of PH associated with MPD: polycythemia vera (8 patients) and essential thrombocythemia (2 patients), followed between 1993 and 2002. The baseline evaluation was established by right-sided heart catheterization, ventilation/perfusion lung scan and pulmonary angiography if required. RESULTS: Six patients had confirmed chronic thromboembolic pulmonary hypertension (CTEPH) and 4 had pulmonary arterial hypertension (PAH) associated with MPD without other risk factors for PAH. The hemodynamic characteristics of CTEPH and PAH associated with MPD were similar. The diagnosis of CTEPH was concomitant to that of MPD in all cases (5 polycythemia vera and 1 essential thrombocythemia). The PAH associated with MPD occurred later in the evolution of the MPD (3 polycythemia vera and 1 essential thrombocythemia) with a median of 162 months after the diagnosis of MPD, and it was associated with myeloid metaplasia (p < 0.01). CONCLUSION: We describe 2 distinct forms of PH in the context of MPD: CTEPH, which is diagnosed at an early stage of the MPD, and PAH, which occurs later in the course of the MPD and is associated with myeloid metaplasia. Progressively increasing dyspnea in a patient with an MPD warrants further investigation to rule out PAH and CTEPH, while a diagnosis of CTEPH warrants ruling out MPD.


Asunto(s)
Hipertensión Pulmonar/complicaciones , Policitemia Vera/complicaciones , Embolia Pulmonar/complicaciones , Trombocitemia Esencial/complicaciones , Adulto , Anciano , Femenino , Humanos , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Policitemia Vera/terapia , Mielofibrosis Primaria/complicaciones , Circulación Pulmonar , Embolia Pulmonar/terapia , Estudios Retrospectivos , Trombocitemia Esencial/terapia
5.
J Neurol ; 265(10): 2251-2259, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30054790

RESUMEN

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.


Asunto(s)
Esclerosis Múltiple/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Esclerosis Cerebral Difusa de Schilder/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/patología , Esclerosis Múltiple/terapia , Estudios Retrospectivos
6.
Leukemia ; 20(10): 1723-30, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16932345

RESUMEN

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Idarrubicina/administración & dosificación , Infusiones Intravenosas , Tiempo de Internación , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Pancitopenia , Cooperación del Paciente , Factores de Riesgo
7.
Gynecol Obstet Fertil ; 35(10): 1047-50, 2007 Oct.
Artículo en Francés | MEDLINE | ID: mdl-17916439

RESUMEN

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.


Asunto(s)
Fertilización In Vitro/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Inducción de la Ovulación/efectos adversos , Femenino , Humanos , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Embarazo , Complicaciones del Embarazo/epidemiología , Recurrencia , Factores de Riesgo
8.
Bone Marrow Transplant ; 37(8): 725-9, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16518433

RESUMEN

A study was conducted to compare the efficiency and toxicity of two peripheral blood stem cell (PBSC) mobilization procedures for newly diagnosed patients with multiple myeloma. Patients from group 1 (n=51) were treated by high-dose cyclophosphamide (HD-CY) plus G-CSF (5 microg/kg/day), and the second group (n=31) by VAD regimen plus G-CSF administration (10 microg/kg/day). Successful mobilization, defined by a minimal count of 2.5 x 10(6) CD34(+) cells/kg collected, was achieved in 96 and 90% of patients in groups 1 and 2, respectively (P=0.15). The mean peripheral blood CD34(+) cells concentration and the mean CD34(+) cells/kg collected were higher in group 2 than in the group 1 (P=0.05). The mean number of leukaphereses necessary to collect a count of 2.5 x 10(6) CD34(+) cells/kg was reduced in group 2 compared to group 1. Adverse events, blood products consumption and time spent in the hospital were significantly greater after HD-CY. In conclusion, VAD plus a G-CSF dose of 10 microg/kg administration seems preferential to HD-CY plus a G-CSF dose of 5 microg/kg for PBSC collection because of equivalent or better efficiency in stem cell mobilization, strong favorable toxicity profile and reduced cost.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Antígenos CD34/biosíntesis , Separación Celular , Ciclofosfamida/metabolismo , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Células Madre/citología , Factores de Tiempo , Resultado del Tratamiento , Vincristina/uso terapéutico
9.
Transfus Clin Biol ; 23(1): 39-44, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26775794

RESUMEN

Plasma therapy consists in bringing to a patient in need - in general suffering a severe, resistant to current therapy, and even lethal infection - plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917-1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013-2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.


Asunto(s)
Inmunización Pasiva/métodos , Infecciones/terapia , Plasma , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/uso terapéutico , Convalecencia , Brotes de Enfermedades , Predicción , Humanos , Inmunización Pasiva/tendencias , Plasma/inmunología , Virosis/epidemiología , Virosis/terapia
10.
Leukemia ; 14(4): 573-5, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10764141

RESUMEN

Splenic lymphoma with villous lymphocytes (SLVL) is a B cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second-line treatment remains questionable. In a retrospective study, we evaluated the efficacy and toxicity of fludarabine (FDR) in 10 SLVL patients. The median duration between diagnosis and treatment was 17 months (range, 1-30). Two patients were previously untreated. The patients received FDR 25 mg/m2/day by venous infusion for 5 days with a median of four cycles of chemotherapy (range, 2-6). All patients were assessable: five patients achieved a good and persistent response after a median follow-up of 14 months (5-31), two achieved a good response but relapsed after a follow-up of 15 and 36 months. One out of the three partial responders have a persistent response. The treatment was well tolerated. FDR appears to be an efficient therapy with a favorable toxicity profile for patients in relapse after splenectomy or resistant to CLB. Furthermore it could constitute an alternative to splenectomy in older patients. A longer follow-up and the study of a larger group of patients are warranted to confirm our findings.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Neoplasias del Bazo/tratamiento farmacológico , Vidarabina/análogos & derivados , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorambucilo/uso terapéutico , Terapia Combinada , Evaluación de Medicamentos , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Linfoma de Células B/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Inducción de Remisión , Estudios Retrospectivos , Esplenectomía , Neoplasias del Bazo/cirugía , Vidarabina/uso terapéutico
11.
Leukemia ; 13(10): 1491-6, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10516747

RESUMEN

We have conducted a phase II outpatient trial testing weekly oral administration of idarubicin (ZAVEDOS-ZVD) alone to determine the rate of objective response and toxicity in poor risk acute myeloid leukemia (AML) patients over 60 years of age. The treatment consisted of three phases: induction, with 20 mg/m2 of ZVD on days 1, 8, 15 and 22; consolidation with 20 mg/m2 of ZVD for 4 weeks; and maintenance with six cycles lasting 3 months and consisting of oral 6 mercapto-purine 2 mg/kg/day, 4 days a week for 2 months; subcutaneous cytarabine 1 mg/kg, once a week for 2 months; and oral ZVD 20 mg/m2 on day 1 and day 8 of the third month. In case of failure after induction course, patients received salvage treatment with 4 weekly oral doses of 40 mg/m2 ZVD. Fifty-one patients with a median age of 76 years were enrolled and could receive induction course. Of these 51 patients, 37 could receive subsequent courses, which consisted either of consolidation, or salvage. Only 11 patients underwent maintenance treatment. Sixty-three percent of patients had to be hospitalized during induction, for a median duration of 14.5 days, and 87% required hospitalization during salvage for a median duration of 17.5 days. Only five patients (38%) required hospitalization during consolidation. There were three toxic deaths (6%), two from hemorrhage and one from pulmonary embolism. The overall response rate was 29%, with 12 patients in complete response (25%) and two in partial response (4%). The median overall survival rate is 4 months for the whole population, and the median DFS is 9.6 months among the 14 responding patients. The results of this trial show that this new weekly schedule of oral ZVD chemotherapy is feasible and effective in poor risk elderly patients with AML. This regimen may be helpful for patients unable to tolerate intensive intravenous regimens, and is a real alternative to palliative treatments.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Inducción de Remisión/métodos , Enfermedad Aguda , Administración Oral , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/farmacocinética , Humanos , Idarrubicina/farmacocinética , Leucemia Mieloide/mortalidad , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
12.
Leukemia ; 17(2): 339-42, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12592333

RESUMEN

Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA --> CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA --> CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.


Asunto(s)
Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucopenia/tratamiento farmacológico , Tretinoina/efectos adversos , Tretinoina/uso terapéutico , Adulto , Edad de Inicio , Antineoplásicos/uso terapéutico , Femenino , Humanos , Leucemia Promielocítica Aguda/sangre , Recuento de Leucocitos , Leucopenia/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome , Resultado del Tratamiento
13.
Leukemia ; 15(11): 1785-91, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11681422

RESUMEN

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.


Asunto(s)
Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Reordenamiento Génico , Genes bcl-1 , Humanos , Inmunofenotipificación , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
14.
Leukemia ; 16(4): 587-93, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11960337

RESUMEN

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Ciclofosfamida/uso terapéutico , Citarabina/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células del Manto/terapia , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Adulto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
15.
Bone Marrow Transplant ; 50(3): 341-7, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25402418

RESUMEN

The faster hematopoietic recovery after autologous peripheral blood SCT (APBSCT) in patients with AML may be offset by an increased relapse risk as compared with autologous BMT (ABMT). The EORTC and GIMEMA Leukemia Groups conducted a trial (AML-10) in which they compared, as second randomization, APBSCT and ABMT in first CR patients without an HLA compatible donor. A total of 292 patients were randomized. The 5-year DFS rate was 41% in the APBSCT arm and 46% in the ABMT arm with a hazard ratio (HR) of 1.17; 95% confidence interval=0.85-1.59; P=0.34. The 5-year cumulative relapse incidence was 56% vs 49% (P=0.26), and the 5-year OS 50% and 55% (P=0.6) in the APBSCT and ABMT groups, respectively. APBSCT was associated with significantly faster recovery of neutrophils and platelets, shorter duration of hospitalization, reduced need of transfusion packed RBC and less days of intravenous antibiotics. In both treatment groups, higher numbers of mobilized CD34+ cells were associated with a significantly higher relapse risk irrespective of the treatment given after the mobilization. Randomization between APBSCT and ABMT did not result in significantly different outcomes in terms of DFS, OS and relapse incidence.


Asunto(s)
Antígenos CD34/metabolismo , Trasplante de Médula Ósea/métodos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Factores de Riesgo , Trasplante Autólogo , Adulto Joven
16.
Bone Marrow Transplant ; 28(8): 799-801, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11781635

RESUMEN

A 45-year-old matched unrelated BMT recipient had sequential mucocutaneous herpes simplex virus (HSV) type 2 infections. Five months after BMT, a penile lesion occurred and was cured using acyclovir, as expected from in vitro susceptibility results. The same lesion recurred 1 month later but worsened with acyclovir. The HSV isolate was resistant to acyclovir (IC(50) = 105 microM), and a nucleotide (G) was added to the thymidine kinase gene leading to a premature stop codon. The lesion improved markedly with foscarnet. During this treatment a second HSV infection occurred on the buttocks 2 weeks after the first one and healed completely with acyclovir. This course correlated with in vitro results of the buttock HSV isolate which was foscarnet-resistant (IC(50) = 300 microg/ml) and acyclovir-sensitive. Surprisingly, no mutation gene of the foscarnet-resistant isolate was detected in the DNA polymerase gene. This case shows that an HSV acyclovir-resistant infection may be followed by an acyclovir-sensitive one. Determination of antiviral susceptibility is needed to monitor the treatment of various HSV infections in immunocompromised BMT recipients.


Asunto(s)
Trasplante de Médula Ósea , Citosina/análogos & derivados , Farmacorresistencia Viral , Herpes Simple/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Organofosfonatos , Simplexvirus/efectos de los fármacos , Aciclovir/farmacología , Aciclovir/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Cidofovir , Terapia Combinada , Ciclosporina/uso terapéutico , Citarabina/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Citosina/farmacología , Resultado Fatal , Foscarnet/farmacología , Foscarnet/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Herpes Genital/complicaciones , Herpes Genital/tratamiento farmacológico , Herpes Genital/virología , Herpes Simple/tratamiento farmacológico , Herpes Simple/virología , Humanos , Hidroxiurea/uso terapéutico , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Interferones/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Compuestos Organofosforados/farmacología , Simplexvirus/aislamiento & purificación , Acondicionamiento Pretrasplante/efectos adversos , Irradiación Corporal Total/efectos adversos
17.
Bone Marrow Transplant ; 18(2): 473-4, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8864468

RESUMEN

We describe a case of Plasmodium falciparum infection in a Comorian patient undergoing BMT. The patient's last visit to an endemic area was 1 year prior to BMT. The donor left the Comoro Islands 2 months before marrow harvesting. They had both had previous episodes of malaria and were seropositive for Plasmodium falciparum. At the time of BMT, blood smears were negative in both the donor and recipient. On day 12 post-BMT the patient was asymptomatic but a blood smear revealed 12.5% parasitemia. We consider that donors and recipients at risk pre-BMT should routinely be given specific treatment before marrow harvesting and conditioning, independent of the appearance of blood smears.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Malaria Falciparum/transmisión , Adulto , Humanos , Masculino , Trasplante Homólogo
18.
Bone Marrow Transplant ; 24(5): 463-6, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10482928

RESUMEN

Harvesting of peripheral blood stem cells (PBSCs) following chemotherapy and G-CSF administration is currently performed for hematological therapies. However, a procedure based on the use of a large quantity of G-CSF is relatively costly. Therefore, we retrospectively compared the effects of two PBSC mobilization procedures in a population with recently diagnosed multiple myeloma. The first procedure consisted of chemotherapy and systematic G-CSF administration (group 1: 24 patients). The second consisted of chemotherapy alone, G-CSF having been administered only in the case of failure of PBSC mobilization or delayed white blood cell (WBC) recovery (group 2: 28 patients). Leukapheresis was performed when WBC recovery reached 1 x 10(9)/l if the peripheral blood CD34+ cell count was over 10/microl. Leukapheresis was maintained until a total of 2.5 x 10(6) CD34+ cells/kg was harvested. A significant difference was observed between the two groups only in regard to the median period of WBC recovery (delayed for group 2) and the number of CD34+ cells/kg collected on the first leukapheresis (higher for group 1) but not to the proportion of patients with failure of PBSC collection. Ten group 2 patients, who had insufficient CD34+ cells after WBC recovery or delayed WBC recovery, received G-CSF which resulted in sufficient PBSC harvesting in nine. To obtain a sufficient CD34+ cell level, the patients without systematic G-CSF administration had more leukaphereses (2.1 vs 1.5) but the mean consumption of G-CSF per patient was eight times less than in the other group. Nonsystematic use of G-CSF before WBC recovery or preferentially its introduction just after, could be an interesting economical alternative in PBSC mobilization but should be assessed by a prospective controlled study of cost/efficacy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Células Sanguíneas , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Células Madre Hematopoyéticas , Leucaféresis , Mieloma Múltiple/sangre , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Esquema de Medicación , Estudios de Evaluación como Asunto , Femenino , Movilización de Célula Madre Hematopoyética/economía , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Prednisona/administración & dosificación , Prednisona/farmacología , Estudios Retrospectivos , Vincristina/administración & dosificación , Vincristina/farmacología
19.
Hematol J ; 2(2): 81-6, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11423999

RESUMEN

PURPOSE: To analyse prognostic factors influencing hematopoietic recovery in patients with aggressive non-Hodgkin's lymphomas prospectively treated with intensive chemotherapy followed by peripheral blood progenitor-cells transplantation. PATIENTS AND METHODS: Untreated patients with at least two unfavorable factors according to the age-adjusted international prognostic index were included in the LNH 93-3 trial. Patients received three cycles of chemotherapy and PBPC were mobilized using filgrastim. On day 60, a BEAM regimen was initiated followed by PBPC rescue. Among the 123 patients analysed, 60 received G-CSF (5 microg/kg/d) after PBPC transplantation at day 1 and 63 did not. RESULTS: Patients received a mean number of 12.4 x 10(6)/kg (1.86-111.5) CD34+ cells. After transplantation, neutrophil counts exceeded 0.5 x 10(9)/l at a median of 12.4 days (7-41 days) and platelet counts exceeded 50 x 10(9)/l at a median of 15.6 days (9-141 days). Platelets recovery > 50 x 10(9)/l was negatively influenced by BM involvement (20 s 14 days; P = 0.04). The number of CD34+ cells infused (> vs < or = 5 x 10(6)/kg) was correlated with faster platelet recovery (18.7 days vs 13.7 days) (P = 0.007). In 26 patients for whom administration of G-CSF was randomized, time to neutrophil recovery was significantly shorter for patients treated with G-CSF: 10 vs 13 days (P = 0.0005). The incidence of grade 3/4 infection, was similar in both groups. CONCLUSION: In the patient population treated with the same first-line regimen, BM involvement and infusion of fewer CD34+ cells delayed platelet recovery. Administration of G-CSF after PBPC significantly reduced neutropenia.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Hematopoyesis/efectos de los fármacos , Linfoma no Hodgkin/terapia , Trasplante de Células Madre de Sangre Periférica , Recuperación de la Función/efectos de los fármacos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
20.
Leuk Lymphoma ; 37(5-6): 623-7, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-11042524

RESUMEN

A 73-year-old woman complained of easy bruising, as a consequence of prolonged bleeding time despite normal platelet counts. Platelet aggregation profile, mepacrine fluorescence test, flow cytometry and transmission electron microscopy studies led to the diagnosis of delta-storage pool deficiency (SPD) A few months later, she developed hyperleucocytosis with immature granulocytes and erythroblasts. The presence of bone marrow fibrosis and clonal cytogenetic abnormalities led to the diagnosis of idiopathic myelofibrosis (IM). Association between SPD and IM has never been reported. The pathogenesis of this unusual association remains unclear and may involve proliferation of abnormal monoclonal stem cells with differentiation into activated megakaryocytes associated with impaired dense granule development and increased cytokines release which may be. involved in myelofibrosis.


Asunto(s)
Deficiencia de Almacenamiento del Pool Plaquetario/complicaciones , Mielofibrosis Primaria/complicaciones , Anciano , Médula Ósea/patología , Aberraciones Cromosómicas , Gránulos Citoplasmáticos/ultraestructura , Femenino , Hemartrosis/etiología , Células Madre Hematopoyéticas/patología , Humanos , Megacariocitos/patología , Pruebas de Función Plaquetaria , Deficiencia de Almacenamiento del Pool Plaquetario/diagnóstico , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/genética , Púrpura/etiología
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