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1.
Haematologica ; 105(5): 1240-1247, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31537695

RESUMEN

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Anemia de Células Falciformes/terapia , Quimerismo , Terapia Genética , Hematopoyesis , Humanos , Quimera por Trasplante , Trasplante Homólogo
2.
Haematologica ; 105(1): 91-101, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31097628

RESUMEN

Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft-versus-host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37; P=0.002) and lower (5-15 vs 20 mg/kg) ATG dose (hazard ratio=4.55; P=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning.


Asunto(s)
Anemia de Células Falciformes , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anciano , Anemia de Células Falciformes/terapia , Quimerismo , Fertilidad , Francia/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Supervivencia sin Progresión , Hermanos , Acondicionamiento Pretrasplante
3.
Blood ; 129(5): 643-649, 2017 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-27899357

RESUMEN

Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedad Aguda , Adulto , Anticuerpos Monoclonales/efectos adversos , Suero Antilinfocítico/efectos adversos , Resistencia a Medicamentos , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Esteroides/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento
4.
Blood ; 124(2): 204-10, 2014 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-24869941

RESUMEN

In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (ie, after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence with or without preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0 episodes/year (IQR, 0-0.81) (P < .01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed to increase durably. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P < .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Púrpura Trombocitopénica Trombótica/prevención & control , Proteínas ADAM/sangre , Proteínas ADAM/deficiencia , Proteínas ADAM/inmunología , Proteína ADAMTS13 , Adulto , Autoanticuerpos/sangre , Quimioprevención/métodos , Estudios Transversales , Femenino , Humanos , Infusiones Intravenosas , Masculino , Púrpura Trombocitopénica Trombótica/sangre , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Prevención Secundaria , Resultado del Tratamiento
5.
Blood ; 123(24): 3739-49, 2014 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-24740809

RESUMEN

With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.


Asunto(s)
Biomarcadores de Tumor/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Adulto , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
7.
Biol Blood Marrow Transplant ; 19(1): 150-5, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22960387

RESUMEN

We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response).


Asunto(s)
Antineoplásicos/administración & dosificación , Benzamidas/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Cromosoma Filadelfia , Piperazinas/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pirimidinas/administración & dosificación , Adolescente , Adulto , Factores de Edad , Antineoplásicos/efectos adversos , Benzamidas/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Tasa de Supervivencia , Factores de Tiempo , Trasplante Autólogo , Trasplante Homólogo , Donante no Emparentado
9.
Crit Care Med ; 40(1): 104-11, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21926591

RESUMEN

OBJECTIVE: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura. DESIGN: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine. SETTING: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France. PATIENTS: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange. INTERVENTION: Add-on rituximab therapy, four infusions over 15 days. MEASUREMENTS AND MAIN RESULTS: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred. CONCLUSIONS: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factores Inmunológicos/uso terapéutico , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Rituximab , Terapia Recuperativa , Insuficiencia del Tratamiento , Resultado del Tratamiento
10.
J Clin Med ; 11(5)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35268291

RESUMEN

A person's sexual and emotional life is greatly impacted after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This topic is not addressed very much by patients and caregivers. Physical, endocrine and genital chronic graft versus host disease (cGVHD)-related disorders are multiple and intertwined with psychological disorders. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) has issued recommendations for a better gynecological monitoring of female recipients after allo-HCT. A patient booklet was also offered to patients in the form of questions and answers to facilitate discussions between patients and caregivers and to improve the management of sexual and emotional life after transplant.

11.
Biol Blood Marrow Transplant ; 17(2): 265-9, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20691799

RESUMEN

The subpopulation of regulatory T cells (Treg) was shown to play a key role in alloreactive responses. In allogeneic hematopoietic stem cell transplantation, several groups tested whether Treg content in transplants correlates with graft-versus-host disease (GVHD) with controversial results. In a retrospective study of 49 consecutive HLA-matched sibling transplantations, we studied the relationship between Treg content in bone marrow transplants and acute GVHD (aGVHD) occurrence. We observed a large variability in Treg in bone marrow grafts. However, contrary to previous observations in peripheral blood stem cells transplantation, we report that the Treg content of allogeneic bone marrow transplantation did not predict the occurrence of aGVHD.


Asunto(s)
Células de la Médula Ósea , Trasplante de Médula Ósea/efectos adversos , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos T Reguladores , Enfermedad Aguda , Adolescente , Adulto , Antígenos CD4/metabolismo , Recuento de Células , Femenino , Histocompatibilidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Hermanos , Adulto Joven
12.
Blood ; 113(17): 3918-24, 2009 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-19109228

RESUMEN

Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials. In 88 cases (62%) there were demonstrated NOTCH1 mutations (42% heterodimerization [HD], 10% HD+proline glutamate serine threonine [PEST], 6% PEST, 2% juxtamembrane mutations, 2% transactivation domain [TAD]) and 34 cases (24%) had FBXW7 mutations (21 cases had both NOTCH1 and FBXW7 mutations); 40 cases (28%) were wild type for both. There was no significant correlation between NOTCH1 and/or FBXW7 mutations and clinico-biologic features. Median event-free survival (EFS) and overall survival (OS) were 36 versus 17 months (P = .01) and not reached versus 32 months (P = .004) in patients with NOTCH1 and/or FBXW7 mutations versus other patients, respectively. Multivariate analysis showed that the presence of NOTCH1/FBXW7 mutations was an independent good prognostic factor for EFS and OS (P = .02 and P = .01, respectively). These data demonstrate that NOTCH1 pathway activation by either NOTCH1 or FBXW7 mutation identifies a large group of patients with a favorable outcome that could justify individual therapeutic stratification for T-ALL.


Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas F-Box/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD , Genotipo , Humanos , Mutación/genética , Fenotipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Pronóstico , Receptor Notch1/metabolismo , Sociedades Médicas , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Ubiquitina-Proteína Ligasas/metabolismo
13.
Transfusion ; 51(8): 1769-78, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21332732

RESUMEN

BACKGROUND: Allogeneic donor natural killer (NK)-cell infusion (NK-DLI) is a promising immunotherapy for patients with hematologic disorders. CASE REPORT: This report describes the case of a patient who received a single haploidentical NK-DLI for a relapse of acute myeloid leukemia (AML) after haploidentical hematopoietic stem cell transplantation. He underwent a cytoreductive, immunosuppressive regimen before NK-DLI and received high-dose interleukin-2 in vivo for 8 weeks afterward. RESULTS: No major adverse effect was observed. Prospective phenotypic and functional studies of the NK cells showed major expansion of infused NK cells and, more importantly, of the alloreactive KIR2DL1+KIR2DL2/DL3-NKG2A- subset, which reached 117×10(6) cells/L on Day +14 after NK-DLI, the greatest expansion of infused alloreactive NK cells reported so far. Infused NK cells conserved their lytic capacities against K562 target cells and primary AML-mismatched blasts. CONCLUSION: We review the literature to clarify these data and to detail the indications for allogeneic NK-DLI, the criteria for determining the most suitable donor, the types of conditioning regimens, and the procedures for selecting and activating NK cells.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales/trasplante , Leucemia Mieloide Aguda/terapia , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Humanos , Inmunoterapia Adoptiva/métodos , Células K562 , Leucemia Mieloide Aguda/inmunología , Masculino , Recurrencia , Trasplante Homólogo
14.
Haematologica ; 95(2): 324-8, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19773266

RESUMEN

The prognostic significance of CD20 expression in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been mostly studied in children and yielded conflicting results. In 143 adults with Philadelphia chromosome-negative BCP-ALL treated in the multicentric GRAALL 2003 trial, CD20 positivity over 20% was observed in 32% of patients. While not influencing complete remission achievement, CD20 expression was associated with a higher cumulative incidence of relapse (CIR) at 42 months (P=0.04), independently of the ALL high-risk subset (P=0.025). Notably, the negative impact of CD20 expression on CIR was only observed in patients with a white blood cell count (WBC) over 30x10(9)/L (P=0.006), while not in those with a lower WBC. In the former subgroup, this impact translated into lower event-free survival (15% vs. 59% at 42 months, P=0.003). CD20 expression thus appears to be associated with a worse outcome, which reinforces the interest of evaluating rituximab combined to chemotherapy in CD20-positive adult BCP-ALL. ClinicalTrials.gov ID, NCT00222027.


Asunto(s)
Antígenos CD20/genética , Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Enfermedad Aguda , Adolescente , Adulto , Ensayos Clínicos como Asunto , Humanos , Recuento de Leucocitos , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Pronóstico , Recurrencia , Adulto Joven
15.
Transfusion ; 50(12): 2649-59, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20576009

RESUMEN

BACKGROUND: Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored. STUDY DESIGN AND METHODS: A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean+1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time. RESULTS: Sixteen patients, who received at least 3 × 10(6) CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p=0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1ß, and IL-6 involved in stem cell homing. CONCLUSION: Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation.


Asunto(s)
Funcionamiento Retardado del Injerto/etiología , Supervivencia de Injerto/fisiología , Trasplante de Células Madre Hematopoyéticas , Recuento de Leucocitos , Leucocitos/fisiología , Adulto , Anciano , Antígenos CD34/metabolismo , Funcionamiento Retardado del Injerto/sangre , Femenino , Supervivencia de Injerto/inmunología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Humanos , Transfusión de Leucocitos , Leucocitos/citología , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Recuperación de la Función/inmunología , Recuperación de la Función/fisiología , Trasplante Autólogo/rehabilitación
16.
Bull Cancer ; 107(12S): S151-S158, 2020 Dec.
Artículo en Francés | MEDLINE | ID: mdl-32747052

RESUMEN

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organises annual workshops in an attempt to harmonise clinical practices among different francophone transplantation centres. The SFGM-TC harmonisation workshops aim at establishing practical guidelines, on the one hand, from data from the literature and international recommendations and, on the other hand, by consensus in the absence of formally proven data. The sexual and emotional life of allogeneic hematopoietic stem cells transplanted (HSCT) patients is often very impacted and remains a subject relatively little addressed by patients and caregivers. This article is an update from a previous workshop and is accompanied by a patient booklet, which will be included in the post allograft follow-up workbook published by the SFGM-TC. The purpose of these two documents is to facilitate discussions between patients and caregivers on the subject and to present proposals for follow-up and tools to better manage the sexual and emotional life of allotransplanted patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/psicología , Salud Mental , Folletos , Educación Sexual/métodos , Conducta Sexual , Congresos como Asunto/organización & administración , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Educación del Paciente como Asunto , Factores Sexuales , Sociedades Médicas
17.
Br J Haematol ; 147(5): 719-28, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19793383

RESUMEN

Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-free survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma Folicular/terapia , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Histocompatibilidad , Prueba de Histocompatibilidad/métodos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento
18.
J Virol ; 82(20): 10143-52, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18684826

RESUMEN

Recovery of human cytomegalovirus (HCMV)-specific T immunity is critical for protection against HCMV disease in the early phase after allogeneic stem cell transplantation (SCT). Using an enzyme-linked immunospot assay with overlapping 15-mer peptides spanning pp65 and immediate-early 1 HCMV proteins, we investigated which HCMV-specific CD8(+) gamma interferon-positive (IFN-gamma(+)) T-cell responses against pp65 and IE-1 were associated with control of HCMV replication in 48 recipients of unmanipulated HLA-matched allografts at 3 months (M3) and 6 months (M6) after SCT and in 23 donors. At M3 after SCT, the magnitude of the pp65-specific IFN-gamma-producing CD8(+) T-cell response was greater in recipients than in donors, regardless of HCMV status. In contrast, expansion of IE-1-specific CD8(+) T cells at M3 was associated with protection against HCMV, and no patient with this expansion had HCMV replication at M3. At M6, the number of HCMV-specific CD8(+) T cells against both pp65 and IE-1 had expanded in all recipients, regardless of their previous levels of HCMV replication. The recipients' HCMV-specific CD8(+) T cells already detectable in related donors were predominantly targeting pp65. In contrast, in 40% of the cases, the HCMV-specific CD8(+) T cells in recipients involved new CD8(+) T-cell specificities undetectable in their related donors and preferentially targeting IE-1. Taken together, these results showed that the delay in reconstituting IE-1-specific CD8(+) T cells is correlated with the lack of protection against HCMV in the first 3 months after SCT. They also show that IE-1 is a major antigenic determinant of the early restoration of protective immunity to HCMV after SCT.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Proteínas Inmediatas-Precoces/inmunología , Trasplante de Células Madre , Trasplante Homólogo/inmunología , Replicación Viral , Adolescente , Adulto , Anciano , Linfocitos T CD8-positivos/fisiología , Diferenciación Celular , Citomegalovirus/fisiología , Femenino , Humanos , Proteínas Inmediatas-Precoces/genética , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/fisiología , Quimera por Trasplante
19.
Leuk Res ; 32(11): 1741-50, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18508120

RESUMEN

Outcome of adult acute lymphoblastic leukemia (ALL) with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA trials, and 109 patients presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%). Eighty-seven patients (84%) with CNS leukemia at diagnosis achieved complete remission (CR). Fifty-three patients underwent stem cell transplantation (SCT): 25 allogeneic SCT, 28 autologous SCT, while 34 continued with chemotherapy alone. Seven-year overall survival (OS) and disease-free survival (DFS) were 34% and 35%, respectively. There were no significant differences in terms of CR, OS and DFS among patients with CNS involvement at diagnosis and those without CNS disease. There were also no differences among the two groups regarding T lineage ALL, B lineage ALL, and among those who underwent SCT. After a first relapse, 38 patients with CNS recurrence (35%) achieved a second CR. The median OS was 6.3 months. Outcome was similar to that of relapsing patients without CNS disease. CNS leukemia in adult ALL is uncommon at diagnosis as well as at the time of first relapse. With intensification therapy, patients with CNS leukemia at diagnosis have a similar outcome than those who did not present with CNS involvement. CNS leukemia at first relapse remains of similar poor prognosis than all other adult ALL in first relapse.


Asunto(s)
Neoplasias del Sistema Nervioso Central/etiología , Recurrencia Local de Neoplasia/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/patología , Terapia Combinada , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Inducción de Remisión , Trasplante de Células Madre , Resultado del Tratamiento
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