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1.
Blood ; 123(15): 2333-42, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24558201

RESUMO

Approximately one-third of patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (HSCT) are cured by this treatment. Treatment failure may be due to transplant complications or relapse. To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or oligoblastic acute myeloid leukemia (AML, <30% marrow blasts) who received an allogeneic HSCT and were reported to the Gruppo Italiano Trapianto di Midollo Osseo registry between 2000 and 2011. Univariate and multivariate survival analyses were performed using Cox proportional hazards regression. High-risk category, as defined by the revised International Prognostic Scoring System (IPSS-R), and monosomal karyotype were independently associated with relapse and lower overall survival after transplantation. On the other hand, older recipient age and high hematopoietic cell transplantation-comorbidity index (HCT-CI) were independent predictors of nonrelapse mortality. Accounting for various combinations of patient's age, IPSS-R category, monosomal karyotype, and HCT-CI, the 5-year probability of survival after allogeneic HSCT ranged from 0% to 94%. This study indicates that IPSS-R risk category and monosomal karyotype are important factors predicting transplantation failure both in MDS and oligoblastic AML. In addition, it reinforces the concept that allogeneic HSCT offers optimal eradication of myelodysplastic hematopoiesis when the procedure is performed before MDS patients progress to advanced disease stages.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/cirurgia , Adolescente , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
2.
Transfusion ; 56(2): 505-10, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26453579

RESUMO

BACKGROUND: Extracorporeal photopheresis (ECP) is a recognized second-line treatment for steroid-refractory chronic graft-versus-host disease (cGVHD). Treatment course is usually long, expensive, and demanding for patients, so predictors for response are needed. We carried out a retrospective study on cGVHD patients treated at our institution with the aim to identify a possible correlation between apheretic yields composition and probability of response. STUDY DESIGN: Patients treated for at least 6 months were eligible for the study. Flow cytometry data, including absolute counts of lymphocytes and their subpopulations in ECP products from cGVHD patients, were collected. For each cell population 1) the median dose per procedure harvested during the first 3 months of treatment and 2) the cumulative dose collected in the same period were compared with clinical response. RESULTS: A total of 726 ECP procedures were performed in 15 patients. Overall response, defined as either a complete response (CR) or a partial response according to National Institutes of Health criteria, was obtained in 10 of 15 patients (66.7%), and CR, in eight of 15 (53.3%). According to Cox regression analysis, the probability of achieving an overall response is significantly correlated with the median number of CD3+, CD3+CD4+, and CD3+CD8+ lymphocytes collected during the early treatment phase (first 3 months). CONCLUSION: Our data suggest that CD3+ cell evaluation in ECP during the early phase of treatment course could predict response and help identify patients who deserve further treatment.


Assuntos
Complexo CD3/sangue , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Resistência a Medicamentos , Doença Enxerto-Hospedeiro/terapia , Fotoferese/métodos , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides
3.
Transfusion ; 54(8): 2028-33, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24588265

RESUMO

BACKGROUND: Peripheral blood (PB) hematopoietic progenitor cells (HPC) collected by apheresis are the first-choice source for allogeneic stem cell transplantation. The target HPC dose is usually considered to be 4 × 10(6) CD34+ cells/kg of the recipient, but higher doses are required in reduced-intensity conditioning and haploidentical transplants. Thus, prolonged stimulation and repeated collections or failure to reach HPC target may occur, increasing risks for donors and recipients. We carried out a retrospective multicenter study on healthy donors, to identify donor variables which may correlate with HPC mobilization. STUDY DESIGN AND METHODS: HPC allogeneic donations from sibling and unrelated donors performed in two centers from 1995 to 2012 were analyzed. We defined a mobilization cutoff of 50 × 10(6) CD34+ cells/L and tested somatic variables, blood counts, and granulocyte-colony-stimulating factor (G-CSF) dose and molecular form. RESULTS: A total of 360 donors were analyzed (male, 201; female, 159; sibling, 348; unrelated, 12; median [range] age, 44.8 [13-80] years). Median peak CD34+ in PB was 54.4 × 10(6) /L (range, 5 × 10(6) -299 × 10(6) ). By multivariate analysis, we identified the following variables to correlate with good mobilization: 1) male sex (p<0.0005); 2) younger age (p=0.007); 3) higher baseline (premobilization) white blood cell (WBC) count (p<0.0005); 4) higher G-CSF dosage (p<0.0005); and 5) use of lenograstim rather than filgrastim (p<0.002). CONCLUSION: In healthy donors it is possible to predict successful HPC mobilization by donor sex, age, WBC count, and G-CSF form and dose. Furthermore, based on these data, it may be possible, at least in parental setting, to modulate G-CSF dosage on the basis of donor characteristics.


Assuntos
Algoritmos , Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Imunofenotipagem , Itália , Lenograstim , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transplante de Células-Tronco de Sangue Periférico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Fatores Sexuais , Adulto Jovem
4.
Am J Hematol ; 88(7): 581-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23606215

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Risco , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo
5.
J Neurol ; 269(10): 5337-5346, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35596795

RESUMO

OBJECTIVE: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients. METHODS: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). RESULTS: Eight of the 11 ALS patients enrolled received the established immunoablative protocol. The procedure was well tolerated and side effects were those expected. One patient died 4 months after the conditioning regimen and another patient underwent tracheotomy just before T3 for a sudden respiratory failure, but he is still alive 4 years after the procedure without being ventilated any more. A third patient died 10 months after conditioning. In the other cases, there was no statistical difference in all functional measures and QoL pre- and post-treatment; however, a transitory slopes' reduction of ALSFRS-R and seated SVC% after the conditioning procedures was reported. Moreover, although not statistically significant, trends of reduction of CD4 + and increment of CD8 + were found. CONCLUSIONS: aHSCT was overall well tolerated, but it was not followed by any significant modification in disease progression. Considering the negative results of this small trial, further studies aimed to evaluate the possible efficacy of the aHSCT using a higher-intensity regimen should be carefully and with caution evaluated.


Assuntos
Esclerose Lateral Amiotrófica , Transplante de Células-Tronco Hematopoéticas , Esclerose Lateral Amiotrófica/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Qualidade de Vida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo
6.
Blood ; 112(3): 895-902, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18497321

RESUMO

We evaluated the impact of World Health Organization (WHO) classification and WHO classification-based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P < .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P < .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Transfusão de Sangue , Classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Prognóstico , Recidiva , Taxa de Sobrevida , Organização Mundial da Saúde
7.
Haematologica ; 95(3): 476-84, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19903678

RESUMO

BACKGROUND: Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. DESIGN AND METHODS: We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. RESULTS: Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. CONCLUSIONS: Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non-relapse mortality. These results indicate that transfusion history should be considered in transplantation decision-making in patients with myelodysplastic syndrome.


Assuntos
Transfusão de Sangue , Transplante de Células-Tronco Hematopoéticas , Sobrecarga de Ferro/prevenção & controle , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Ferritinas/sangue , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Sobrecarga de Ferro/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
J Clin Oncol ; 34(30): 3627-3637, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27601546

RESUMO

PURPOSE: The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. PATIENTS AND METHODS: We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. RESULTS: Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from .003 to .035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was an independent predictor of posttransplantation outcome (P = .013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. CONCLUSION: Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.

9.
Haematologica ; 89(3): 361-3, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15020279

RESUMO

We report a high incidence of neutropenia in patients treated with rituximab prior to and following autologous stem cell transplantation (ASCT). Fourteen patients with follicular or mantle-cell lymphoma were treated with high dose (HD) therapy followed by an in vivo-purged autologous graft.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/etiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto , Anticorpos Monoclonais Murinos , Purging da Medula Óssea/efeitos adversos , Feminino , Humanos , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Rituximab , Transplante Autólogo
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