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1.
J Intern Med ; 285(4): 446-454, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30561052

RESUMO

BACKGROUND: We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML). METHODS: Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS: One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS: We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
2.
J Intern Med ; 283(2): 178-189, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28977716

RESUMO

BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Adulto Jovem
3.
J Intern Med ; 283(4): 371-379, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29214689

RESUMO

BACKGROUND: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. MATERIALS AND METHODS: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. RESULTS: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
4.
Ann Dermatol Venereol ; 145(11): 649-658, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30098818

RESUMO

BACKGROUND: Immunotherapies using anti-CTLA4 and anti-PD1 antibodies have revolutionised the management of patients with advanced melanoma. The aim of our study was to analyse the efficacy and safety of immunotherapies in patients with advanced melanoma under real-life conditions. METHODS: We conducted a monocentric, retrospective, observational study that included all patients treated with immunotherapies (ipilimumab, i.e. ipi; nivolumab, i.e. niv and pembrolizumab, i.e. pbr) for advanced melanoma with exclusion of primary mucosal or ocular melanoma. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 110 patients were included. Median PFS was better in the anti-PD1 group than in the anti-CTLA4 group (3.9 months vs. 2.9 months, P=0.025). The frequency of adverse events of any grade was 53.4% with ipi, 66.7% with niv and 75% with pbr. DISCUSSION: Our study shows slightly inferior efficacy data vs. clinical trials of ipi and niv because patients were presenting more severe illness at inclusion. Nevertheless, the study argues in favour of the superiority of anti-PD1 antibodies vs. anti-CTLA4 antibodies in terms of PFS and best overall response. Moreover, our study exhibits safety data comparable to those from clinical trials except for a lower frequency with ipi. CONCLUSION: Our efficacy and safety data obtained under real-life conditions are reassuring since they are consistent with data already published.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Melanoma/mortalidade , Melanoma/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Quimioterapia Combinada , Feminino , França/epidemiologia , Humanos , Infusões Intravenosas , Ipilimumab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Radiocirurgia , Radioterapia Adjuvante , Estudos Retrospectivos
5.
Ann Oncol ; 28(9): 2191-2198, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911060

RESUMO

BACKGROUND: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. PATIENTS AND METHODS: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101). RESULTS: In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy. CONCLUSION: We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/terapia , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Vidarabina/administração & dosagem , Adulto Jovem
6.
Ann Hematol ; 96(6): 943-950, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28374163

RESUMO

The DHAP regimen (high-dose cytarabine in combination with dexamethasone and cisplatin) with or without rituximab (DHAP+/-R) is one of the most common regimens in daily practice. It is considered the standard treatment for relapse or refractory Hodgkin's and non-Hodgkin's lymphoma (NHL). Cisplatin nephrotoxicity is a major concern, and other platinum compounds are being tried. We performed a monocentric retrospective analysis to evaluate the use of carboplatin, so-called DHAC+/-R regimen. The purpose was to assess the toxicity of the DHAC+/-R regimen in real-life. The Dexamethasone, Cytarabine, Carboplatin (DHAC) regimen consisted of carboplatin AUC = 5 mg/ml/min (targeted area under the curve with Calvert's formula) on day 1, cytarabine 2 g/m2 twice a day on day 2 and IV dexamethasone 40 mg from days 1 to 4. Rituximab was administrated at 375 mg/m2 on day 1 for CD20+ NHL. The interval between courses was 21 days. During the period considered, 199 patients received DHAC+/-R. For the entire cohort, median follow-up is 24 months (range, 2-82), median OS is not reached (NR), estimated 2-year OS is 75% (95% CI, 69-83) and median progression-free survival (PFS) is 46 months (95% CI, 22-NA). Of 144 patients scheduled for autologous stem cell transplantation (ASCT), 102 (71%, NA = 2) were in response after DHAC+/-R and all except 4 underwent ASCT. Grade ≥ 3 haematological toxicities were mainly thrombocytopenia (n = 101) and anaemia (n = 95). Grade ≥ 3 neutropenia occurred in 10 patients. No grade ≥ 3 renal and one grade 3 neurological toxicity were reported. DHAC+/-R is feasible in daily practice, provides good response rates and jeopardises neither stem cell collection nor ASCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/terapia , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Indução de Remissão , Estudos Retrospectivos , Rituximab/administração & dosagem , Transplante de Células-Tronco/métodos , Trombocitopenia/induzido quimicamente , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
7.
Ann Hematol ; 95(8): 1287-93, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27297970

RESUMO

We retrospectively evaluated the role of rituximab (R) in maintenance treatment after autologous stem cell transplantation performed in patients with relapsed follicular lymphoma. We compared the outcome of 67 follicular lymphoma (FL) patients according to the use of rituximab maintenance (RM) or not. All patients received rituximab plus chemotherapy before autologous stem-cell transplantation (ASCT). Patients received median of two lines of prior therapy. The RM schedule was one injection of rituximab every 3 months for 2 years. Median follow-up is 4.6 years. The 3-year progression-free survival (PFS) after ASCT was 86 % with RM vs. 46 % without (p = 0.0045). Median is not reached in the RM arm vs. 31 months in non-RM arm. The 3-year OS was 96 % with RM vs. 78 % without (p = 0.059). The present monocentric study shows that 2 years of RM after ASCT significantly increases response duration for non-naive rituximab relapsed FL patients compared with observation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/patologia , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Período Pós-Operatório , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Rituximab/administração & dosagem , Fatores de Tempo , Transplante Autólogo , Adulto Jovem
9.
Ann Oncol ; 26(5): 987-991, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25688058

RESUMO

BACKGROUND: Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases. PATIENTS AND METHODS: The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle. RESULTS: Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients. CONCLUSION: Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.


Assuntos
Ablação por Cateter , Neoplasias Pulmonares/cirurgia , Metastasectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Feminino , França , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Metastasectomia/efeitos adversos , Metastasectomia/mortalidade , Pessoa de Meia-Idade , Seleção de Pacientes , Radiografia Intervencionista , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
10.
Ann Oncol ; 26(2): 386-92, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25392158

RESUMO

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases with dismal outcome when treated with chemotherapy alone. Because allogeneic stem-cell transplantation (allo-SCT) can cure relapse/refractory patients, we hypothesized that upfront allo-SCT may provide a better outcome. Therefore, all patients that presented with advanced PTCL in our institution at diagnosis were scheduled to undergo upfront allo-SCT after induction chemotherapy. PATIENTS AND METHODS: The aim of the present work was to assess the feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly diagnosed PTCL patients were scheduled to receive upfront allo-SCT. A human leukocyte antigen-matched donor was found for 42 patients: related to the patient in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in 7 cases. RESULTS: After induction chemotherapy, 17 patients reached complete remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the 1 and 2-year overall survival (OS) rates were 59% [95% confidence interval (CI) 47-75] and 55% (95% CI 43-71), respectively. The most frequent reason we did not proceed to allo-SCT was disease progression or insufficient response after induction. For transplanted patients, the 1- and 2-year OS were 76% (95% CI 62-93) and 72.5% (95% CI 58-91), respectively. Toxicity-related mortality (TRM) 1 year after allo-SCT was only 8.2% (95% CI 0-18.5). The 2-year progression-free survival (PFS) rate of patients who did not proceed to allo-SCT (n = 20) was below 30%. The disease status at the time of transplantation was a strong predictive marker for both PFS and OS in transplant patients. CONCLUSIONS: Upfront allo-SCT in PTCLs is feasible with low TRM, and it provides long-term disease control. However, one-third of patients remain chemo-refractory and, thus, new therapeutic approaches are warranted. The role of upfront allo-SCT compared with other therapeutic approaches in PTCLs requires investigation in randomized studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
12.
Pathol Biol (Paris) ; 62(4): 180-4, 2014 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24973859

RESUMO

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.


Assuntos
Haplótipos , Teste de Histocompatibilidade , Transplante de Células-Tronco/normas , Doadores de Tecidos , Transplante Homólogo/normas , Adulto , Idoso , Animais , Transplante de Medula Óssea , Ciclofosfamida , Seleção do Doador , França , Humanos , Imunossupressores , Pessoa de Meia-Idade , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante , Transplante Homólogo/métodos
13.
Pathol Biol (Paris) ; 62(4): 185-9, 2014 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24954121

RESUMO

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.


Assuntos
Haplótipos , Teste de Histocompatibilidade , Transplante de Células-Tronco/normas , Doadores de Tecidos , Transplante Homólogo/normas , Transplante de Medula Óssea , Seleção do Doador , França , Humanos , Imunossupressores , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante , Transplante Homólogo/métodos
14.
Bone Marrow Transplant ; 59(2): 232-238, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38007531

RESUMO

Allogeneic haematopoietic cell transplantation (alloHCT) has curative potential counterbalanced by its toxicity. Prognostic scores fail to include current era patients and alternative donors. We examined adult patients from the EBMT registry who underwent alloHCT between 2010 and 2019 for oncohaematological disease. Our primary objective was to develop a new prognostic score for overall mortality (OM), with a secondary objective of predicting non-relapse mortality (NRM) using the OM score. AI techniques were employed. The model for OM was trained, optimized, and validated using 70%, 15%, and 15% of the data set, respectively. The top models, "gradient boosting" for OM (AUC = 0.64) and "elasticnet" for NRM (AUC = 0.62), were selected. The analysis included 33,927 patients. In the final prognostic model, patients with the lowest score had a 2-year OM and NRM of 18 and 13%, respectively, while those with the highest score had a 2-year OM and NRM of 82 and 93%, respectively. The results were consistent in the subset of the haploidentical cohort (n = 4386). Our score effectively stratifies the risk of OM and NRM in the current era but do not significantly improve mortality prediction. Future prognostic scores can benefit from identifying biological or dynamic markers post alloHCT.


Assuntos
Inteligência Artificial , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Transplante Homólogo , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/métodos , Prognóstico , Doença Crônica , Estudos Retrospectivos
15.
Pathol Biol (Paris) ; 61(4): 149-51, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24011959

RESUMO

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of virus respiratory syncytial virus (RSV), human herpes virus 6 (HHV6) or adenovirus allogeneic Stem Cell Transplantation.


Assuntos
Infecções por Adenoviridae/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/terapia , Infecções por Roseolovirus/terapia , Ativação Viral/fisiologia , Adenoviridae/fisiologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/etiologia , Consenso , Seleção do Doador/normas , Transplante de Células-Tronco Hematopoéticas/normas , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Herpesvirus Humano 6/fisiologia , Humanos , Terapia de Imunossupressão/normas , Terapia de Imunossupressão/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/etiologia , Vírus Sinciciais Respiratórios/fisiologia , Infecções por Roseolovirus/epidemiologia , Infecções por Roseolovirus/etiologia , Transplante Homólogo
16.
Biol Blood Marrow Transplant ; 18(2): 250-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21745455

RESUMO

The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.


Assuntos
Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Neoplasias Hematológicas/sangue , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo
17.
Colloids Surf B Biointerfaces ; 213: 112359, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35144082

RESUMO

The development of blood-interacting surfaces is critical to fabricate biomaterials for medical use, such as prostheses, implants, biosensors, and membranes. For instance, thrombosis is one of the leading clinical problems when polymer-based materials interact with blood. To overcome this limitation is necessary to develop strategies that limit platelets adhesion and activation. In this work, hyaluronan (HA)/chitosan (Chi) based-films, recently reported in the literature as platforms for tumor cell capture, were developed and, subsequently, functionalized with sulfated chitosan (ChiS) using a layer-by-layer technique. ChiS, when compared to native Chi, presents the unique abilities to confer anti-thrombogenic properties, to reduce protein adsorption, and also to limit calcification. Film physicochemical characterization was carried out using FTIR and XPS for chemical composition assessment, AFM for the surface morphology, and contact angle for hydrophilicity evaluation. The deposition of ChiS monolayer promoted a decrease in both roughness and hydrophilicity of the HA/Chi films. In addition, the appearance of sulfur in the chemical composition of ChiS-functionalized films confirmed the film modification. Biological assay indicated that the incorporation of sulfated groups limited platelet adhesion, mainly because a significant reduction of platelets adhesion to ChiS-functionalized films was observed compared to HA/Chi films. On balance, this work provides a new insight for the development of novel antithrombogenic biomaterials, opening up new possibilities for devising blood-interaction surfaces.


Assuntos
Quitosana , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Ácido Hialurônico/química , Polissacarídeos/química , Sulfatos , Propriedades de Superfície
18.
Bone Marrow Transplant ; 56(9): 2160-2172, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33911203

RESUMO

We performed a retrospective assessment of patient- and transplant-specific characteristics and outcomes for 4142 patients undergoing allogeneic haematopoietic cell transplant for myelofibrosis between 1995 and 2018 across 278 centres. Activity increased steadily across the four analysed eras (<2006, 2006-2010, 2011-2014 and 2015-2018). Median recipient age increased over time between the earliest and most recent cohort (49.4 years (range, 20.1-68) versus 59.3 years (range, 18.1-78.1). Increasing number of patients with a Karnofsky performance status <90 underwent transplant over time. Increased utilisation of matched unrelated donors was apparent (<2006, 22.5% versus 2015-18, 45.2%; p < 0.001). Decreased use of myeloablative conditioning, increased use of busulphan-based platforms and anti-thymocyte globulin was evident. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased over time (p = 0.027) as did rates of chronic (c) GVHD, predominantly extensive cGVHD (<2006, 36% (31-41%) versus 2015-18, 23% (21-25%); p = 0.001). Overall, significant factors associated with worse overall survival and non-relapse mortality (NRM) remained older age, use of donors other than matched sibling, recipient CMV seropositivity and a lower Karnofsky performance status (<90). Multivariable analysis demonstrated improvements in overall survival and reductions in relapse risk over time with stable NRM rates despite increasing numbers of older, less fit patients and use of unrelated donors.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto Jovem
20.
Eur Radiol ; 20(4): 1003-10, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19862535

RESUMO

OBJECTIVE: To study the sensitivity of MRI performed utilising vaginal and rectal opacification with ultrasound gel in the detection of deep pelvic endometriosis. MATERIAL AND METHODS: This was a prospective monocentric study. All patients evaluated by the gynaecologist for pelvic pain, endometriosis or infertility were included. Axial and sagittal T2-weighted images were performed both with and without vaginal and rectal opacification with ultrasound gel. Three radiologists, all blinded, interpreted the images with a minimum of 15 days between the two readings. MRI performance with and without vaginal and rectal opacification was evaluated by calculating sensitivity, specificity and both positive and negative predictive values. RESULTS: Seventy-eight patients were included. Among these, 31 patients had deep pelvic endometriosis of which 24 were confirmed by laparoscopy. Seventy-six locations of deep pelvic endometriosis were discovered on MRI. For the three reviewers there was a significant improvement in sensitivity between pre- and post-contrast MRI (p < 0.0002). CONCLUSION: Opacification of the vagina and rectum significantly improved the sensitivity of MRI for the detection of deep pelvic endometriosis by expanding the vagina and rectum, thus allowing better delineation of the pelvic organs. This was especially apparent for lesions localised to the vagina and rectovaginal septum.


Assuntos
Meios de Contraste , Endometriose/diagnóstico , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Pelve/patologia , Reto/patologia , Vagina/patologia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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